Articoli di riviste: "SRD5A1"

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Khantham, Chiranan, Wipawadee Yooin, Korawan Sringarm, Sarana Rose Sommano, Supat Jiranusornkul, Francisco David Carmona, Wutigri Nimlamool, Pensak Jantrawut, Pornchai Rachtanapun e Warintorn Ruksiriwanich. "Effects on Steroid 5-Alpha Reductase Gene Expression of Thai Rice Bran Extracts and Molecular Dynamics Study on SRD5A2". Biology 10, n. 4 (11 aprile 2021): 319. http://dx.doi.org/10.3390/biology10040319.

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Steroid 5-alpha reductases (SRD5As) are responsible for the conversion of testosterone to dihydrotestosterone, a potent androgen, which is the aetiologic factor of androgenetic alopecia. This study aimed to compare the SRD5A gene expression suppression activity exerted by Thai rice bran extracts and their components and investigate the interactional mechanism between bioactive compounds and SRD5A2 using molecular dynamics (MD) simulation. Bran of Oryza sativa cv. Tubtim Chumphae (TRB), Yamuechaebia Morchor (YRB), Riceberry (RRB), and Malinil Surin (MRB), all rice milling by-products, was solvent-extracted. The ethanolic extract of TRB had the highest sum of overall bioactive compounds (γ-oryzanol; α-, β-, and γ-tocopherol; phenolics; and flavonoids). Among all extracts, TRB greatly downregulated the expression of SRD5A1, SRD5A2, and SRD5A3; there were no significant differences between TRB and finasteride regarding SRD5A suppression. The linear relationship and principal component analysis supported that the α-tocopherol content was correlated with the SRD5A suppression exerted by TRB. Furthermore, MD simulation demonstrated that α-tocopherol had the highest binding affinity towards SRD5A2 by interacting with residues Phe118 and Trp201. Our findings indicate that α-tocopherol effectively downregulates the expression of SRD5A genes and inhibits SRD5A2 activity, actions that are comparable to standard finasteride. TRB, a source of α-tocopherol, could be developed as an anti-hair loss product.

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Das, Kakoli, Pia D. N. Lorena, Lai Kuan Ng, Diana Lim, Liang Shen, Woei Yun Siow, Ming Teh, Juergen K. V. Reichardt e Manuel Salto-Tellez. "Differential expression of steroid 5α-reductase isozymes and association with disease severity and angiogenic genes predict their biological role in prostate cancer". Endocrine-Related Cancer 17, n. 3 (settembre 2010): 757–70. http://dx.doi.org/10.1677/erc-10-0022.

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The biological role of steroid 5α-reductase isozymes (encoded by the SRD5A1 and SRD5A2 genes) and angiogenic factors that play important roles in the pathogenesis and vascularization of prostate cancer (PC) is poorly understood. The sub-cellular expression of these isozymes and vascular endothelial growth factor (VEGF) in PC tissue microarrays (n=62) was examined using immunohistochemistry. The effect of SRD5A inhibition on the angiogenesis pathway genes in PC was also examined in prostate cell lines, LNCaP, PC3, and RWPE-1, by treating them with the SRD5A inhibitors finasteride and dutasteride, followed by western blot, quantitative PCR, and ELISA chip array techniques. In PC tissues, nuclear SRD5A1 expression was strongly associated with higher cancer Gleason scores (P=0.02), higher cancer stage (P=0.01), and higher serum prostate specific antigen (PSA) levels (P=0.01), whereas nuclear SRD5A2 expression was correlated with VEGF expression (P=0.01). Prostate tumor cell viability was significantly reduced in dutasteride-treated PC3 and RWPE-1 cells compared with finasteride-treated groups. Expression of the angiogenesis pathway genes transforming growth factor β 1 (TGFB1), endothelin (EDN1), TGFα (TGFA), and VEGFR1 was upregulated in LNCaP cells, and at least 7 out of 21 genes were upregulated in PC3 cells treated with finasteride (25 μM). Our findings suggest that SRD5A1 expression predominates in advanced PC, and that inhibition of SRD5A1 and SRD5A2 together was more effective in reducing cell numbers than inhibition of SRD5A2 alone. However, these inhibitors did not show any significant difference in prostate cell angiogenic response. Interestingly, some angiogenic genes remained activated after treatment, possibly due to the duration of treatment and tumor resistance to inhibitors.

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Goodarzi, Mark O., Nissar A. Shah, Heath J. Antoine, Marita Pall, Xiuqing Guo e Ricardo Azziz. "Variants in the 5α-Reductase Type 1 and Type 2 Genes Are Associated with Polycystic Ovary Syndrome and the Severity of Hirsutism in Affected Women". Journal of Clinical Endocrinology & Metabolism 91, n. 10 (1 ottobre 2006): 4085–91. http://dx.doi.org/10.1210/jc.2006-0227.

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Abstract Context: Despite the importance of dihydrotestosterone in androgen action, polymorphisms in the genes for the two isoforms of 5α-reductase (SRD5A1 and SRD5A2) have not been evaluated as risk factors for polycystic ovary syndrome (PCOS). Objective: The objective of the study was to test the hypothesis that haplotypes in the SRD5A1 and SRD5A2 genes are risk factors for PCOS and the severity of hirsutism in affected women. Design: PCOS and control subjects were genotyped for seven single-nucleotide polymorphisms in SRD5A1 and eight single-nucleotide polymorphisms in SRD5A2. Haplotypes were determined and tested for association with PCOS diagnosis and component phenotypes. Setting: Subjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham; control subjects were recruited from the general surrounding community. Genotyping took place at Cedars-Sinai Medical Center in Los Angeles. Participants: A total of 287 White women with PCOS and 187 controls participated. Main Measurements: SRD5A1 and SRD5A2 genotype, quantitative hirsutism score, and hormonal and metabolic phenotypes were assessed. Results: Haplotypes within both genes were associated with PCOS risk. The Leu allele of the Val89Leu variant in SRD5A2 was associated with protection against PCOS; this allele is known to modestly reduce 5α-reductase activity. Haplotypes in SRD5A1 but not SRD5A2 were also associated with the degree of hirsutism in affected women. Conclusions: This study presents genetic evidence suggesting an important role of both isoforms of 5α-reductase in the pathogenesis of PCOS. That only SRD5A1 haplotypes were associated with hirsutism suggests that only this isoform is important in the hair follicle.

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Ruksiriwanich, Warintorn, Chiranan Khantham, Pichchapa Linsaenkart, Tanakarn Chaitep, Pensak Jantrawut, Chuda Chittasupho, Pornchai Rachtanapun et al. "In Vitro and In Vivo Regulation of SRD5A mRNA Expression of Supercritical Carbon Dioxide Extract from Asparagus racemosus Willd. Root as Anti-Sebum and Pore-Minimizing Active Ingredients". Molecules 27, n. 5 (24 febbraio 2022): 1535. http://dx.doi.org/10.3390/molecules27051535.

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Oily skin from overactive sebaceous glands affects self-confidence and personality. There is report of an association between steroid 5-alpha reductase gene (SRD5A) expression and facial sebum production. There is no study of the effect of Asparagus racemosus Willd. root extract on the regulation of SRD5A mRNA expression and anti-sebum efficacy. This study extracted A. racemosus using the supercritical carbon dioxide fluid technique with ethanol and investigated its biological compounds and activities. The A. racemosus root extract had a high content of polyphenolic compounds, including quercetin, naringenin, and p-coumaric acid, and DPPH scavenging activity comparable to that of the standard L-ascorbic acid. A. racemosus root extract showed not only a significant reduction in SRD5A1 and SRD5A2 mRNA expression by about 45.45% and 90.86%, respectively, but also a reduction in the in vivo anti-sebum efficacy in male volunteers, with significantly superior percentage changes in facial sebum production and a reduction in the percentages of pore area after 15 and 30 days of treatment. It can be concluded that A. racemosus root extract with a high content of polyphenol compounds, great antioxidant effects, promising downregulation of SRD5A1 and SRD5A2, and predominant facial sebum reduction and pore-minimizing efficacy could be a candidate for an anti-sebum and pore-minimizing active ingredient to serve in functional cosmetic applications.

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Chen, Erbao, Jing Yi, Qingqi Ren, Yuanna Mi, Zhe Gan e Jikui Liu. "Overexpression of SRD5A3 in Hepatocellular Carcinoma and Its Molecular Mechanism: A Study of Bioinformatics Exploration Analysis with Experimental Verification". Evidence-Based Complementary and Alternative Medicine 2022 (16 settembre 2022): 1–14. http://dx.doi.org/10.1155/2022/7853168.

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Background. Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and more prevalent among males than females. However, the biological role of enzyme 5α-reductase (SRD5A3), which plays a critical role in the androgen receptor signaling pathway during HCC development, remains poorly understood. Methods. ONCOMINE, GEPIA, UALCAN, and Kaplan–Meier Plotter were used to analyze the expression and prognostic value of SRD5A3 in HCC. STRING and Metascape were applied to analyze potential target and molecular pathways underlying SRD5A3 in HCC. A real-time quantitative reverse transcription-polymerase chain reaction was used to validate the downstream target expression of SRD5A3. Results. The expression of SRD5A3 was significantly overexpressed in HCC tissues compared with normal tissues, while the expression of SRD5A1 and SRD5A2 were downregulated in multiple public datasets. It may be that the low methylation of the SRD5A3 promoter leads to its overexpression. The level of SRD5A3 tended to be higher expressed in clinical samples with advanced stage and positive node metastasis. Furthermore, the patients with higher SRD5A3 were remarkably associated with poorer overall survival and disease-free survival in the TCGA data. In addition, the increased mRNA expression of SRD5A3 could predict poorer overall survival in Kaplan–Meier Plotter database including different patient cohorts. Moreover, HCC patients with higher level of SRD5A3 had significantly shorter recurrence-free survival, progression-free survival, and disease-specific survival. Furthermore, enrichment analysis demonstrated that multiple processes, such as steroid hormone biosynthesis, lipid biosynthetic process, and androgen metabolic process, were affected by SRD5A1-3 alterations. In vitro experiments showed that the expression of SRD5A3 was increased in HCC tissues than that in adjacent tissues. SRD5A3 silencing promoted the expression of DOLK in two HCC cell lines. Conclusions. This study identified SRD5A3/DOLK as a novel axis to regulate HCC development.

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Basaria, Shehzad, Ravi Jasuja, Grace Huang, Whitney Wharton, Hong Pan, Karol Pencina, Zhuoying Li et al. "Characteristics of Men Who Report Persistent Sexual Symptoms After Finasteride Use for Hair Loss". Journal of Clinical Endocrinology & Metabolism 101, n. 12 (23 settembre 2016): 4669–80. http://dx.doi.org/10.1210/jc.2016-2726.

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Context: Some men who use finasteride for hair loss report persistent sexual and other symptoms after discontinuing finasteride therapy. Objective: To determine whether these persistent symptoms after discontinuation of finasteride use are due to androgen deficiency, decreased peripheral androgen action, or persistent inhibition of steroid 5α-reductase (SRD5A) enzymes. Participants: Finasteride users, who reported persistent sexual symptoms after discontinuing finasteride (group 1); age-matched finasteride users who did not report sexual symptoms (group 2); and healthy men who had never used finasteride (group 3). Outcomes: Sexual function, mood, affect, cognition, hormone levels, body composition, functional magnetic resonance imaging (fMRI) response to sexually and affectively valenced stimuli, nucleotide sequences of androgen receptor (AR), SRD5A1, and SRD5A2; expression levels of androgen-dependent genes in skin. Setting: Academic medical center. Results: Symptomatic finasteride users were similar in body composition, strength, and nucleotide sequences of AR, SRD5A1, and SRD5A2 genes to asymptomatic finasteride users and nonusers. Symptomatic finasteride users had impaired sexual function, higher depression scores, a more negative affectivity balance, and more cognitive complaints than men in groups 2 and 3 but had normal objectively assessed cognitive function. Testosterone, dihydrotestosterone, 5α-androstane-3α,17β-diol-glucuronide, testosterone to dihydrotestosterone and androsterone glucuronide to etiocholanolone glucuronide ratios, and markers of peripheral androgen action and expression levels of AR-dependent genes in skin did not differ among groups. fMRI blood oxygen level-dependent responses to erotic and nonerotic stimuli revealed abnormal function in brain circuitry linked to sexual arousal and major depression. Conclusions: We found no evidence of androgen deficiency, decreased peripheral androgen action, or persistent peripheral inhibition of SRD5A in men with persistent sexual symptoms after finasteride use. Symptomatic finasteride users revealed depressed mood and fMRI findings consistent with those observed in depression.

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Melcangi, Roberto Cosimo, Livio Casarini, Marco Marino, Daniele Santi, Samantha Sperduti, Silvia Giatti, Silvia Diviccaro et al. "Altered methylation pattern of the SRD5A2 gene in the cerebrospinal fluid of post-finasteride patients: a pilot study". Endocrine Connections 8, n. 8 (agosto 2019): 1118–25. http://dx.doi.org/10.1530/ec-19-0199.

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Context Post-finasteride syndrome (PFS) occurs in patients with androgenic alopecia after suspension of the finasteride treatment, leading to a large variety of persistent side effects. Despite the severity of the clinical picture, the mechanism underlying the PFS symptoms onset and persistence is still unclear. Objective To study whether epigenetic modifications occur in PFS patients. Methods Retrospective analysis of a multicentric, prospective, longitudinal, case–control clinical trial, enrolling 16 PFS patients, compared to 20 age-matched healthy men. Main outcomes were methylation pattern of SRD5A1 and SRD5A2 promoters and concentration of 11 neuroactive steroids, measured by liquid chromatography-tandem mass spectrometry, in blood and cerebrospinal fluid (CSF) samples. Results SRD5A1 and SRD5A2 methylation analysis was performed in all blood samples (n = 16 PFS patients and n = 20 controls), in 16 CSF samples from PFS patients and in 13 CSF samples from controls. The SRD5A2 promoter was more frequently methylated in CSF of PFS patients compared to controls (56.3 vs 7.7%). No promoter methylation was detected in blood samples in both groups. No methylation occurred in the SRD5A1 promoter of both groups. Unmethylated controls compared to unmethylated SRD5A2 patients showed higher pregnenolone, dihydrotestosterone and dihydroprogesterone, together with lower testosterone CSF levels. Andrological and neurological assessments did not differ between methylated and unmethylated subjects. Conclusions For the first time, we demonstrate a tissue-specific methylation pattern of SRD5A2 promoter in PFS patients. Although we cannot conclude whether this pattern is prenatally established or induced by finasteride treatment, it could represent an important mechanism of neuroactive steroid levels and behavioural disturbances previously described in PFS.

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Ruksiriwanich, Warintorn, Chiranan Khantham, Anurak Muangsanguan, Yuthana Phimolsiripol, Francisco J. Barba, Korawan Sringarm, Pornchai Rachtanapun et al. "Guava (Psidium guajava L.) Leaf Extract as Bioactive Substances for Anti-Androgen and Antioxidant Activities". Plants 11, n. 24 (14 dicembre 2022): 3514. http://dx.doi.org/10.3390/plants11243514.

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Leaves of guava (Psidium guajava L.) have been used in Thai folk medicine without any supporting evidence as a traditional herbal remedy for hair loss. Androgenetic alopecia (AGA) is chronic hair loss caused by effects of androgens in those with a genetic predisposition, resulting in hair follicle miniaturization. Our objectives were to provide the mechanistic assessment of guava leaf extract on gene expressions related to the androgen pathway in well-known in vitro models, hair follicle dermal papilla cells (HFDPC), and human prostate cancer cells (DU-145), and to determine its bioactive constituents and antioxidant activities. LC-MS analysis demonstrated that the main components of the ethanolic extract of guava leaves are phenolic substances, specifically catechin, gallic acid, and quercetin, which contribute to its scavenging and metal chelating abilities. The guava leaf extract substantially downregulated SRD5A1, SRD5A2, and SRD5A3 genes in the DU-145 model, suggesting that the extract could minimize hair loss by inhibiting the synthesis of a potent androgen (dihydrotestosterone). SRD5A suppression by gallic acid and quercetin was verified. Our study reveals new perspectives on guava leaf extract’s anti-androgen properties. This extract could be developed as alternative products or therapeutic adjuvants for the treatment of AGA and other androgen-related disorders.

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Cortés-Pavía, Iván, Abel Moreno-Cárcamo, Abraham Landa-Piedra e Marisa Cabeza. "Largo trabajo y mucho que resolver aún sobre las isoenzimas de la 5-alfa reductasa Revisión bibliográfica". Latin American Journal of Development 6, n. 2 (7 agosto 2024): e2358. http://dx.doi.org/10.46814/lajdv6n2-009.

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Este trabajo revisa los principales artículos relacionados con la actividad de la enzima 5α-reductasa (SRD5A) y las patologías andrógeno-dependientes como la hiperplasia prostática benigna, el cáncer de próstata, acné y la calvicie androgénica entre otras. Con este propósito, se revisaron diferentes plataformas como Medline, Scopus y Science Direct, utilizando como indicadores las palabras 5α-reductasa, isoenzimas y patologías andrógeno- dependientes. Con esta clasificación se encontraron artículos clásicos de décadas anteriores y nuevos artículos en donde aparece ya descrita, la estructura de la 5α-reductasa, que en décadas anteriores no había podido ser cristalizada e identificada por rayos X. Además de las dos isoenzimas principales de la SRD5A, aparece en la literatura una tercera isoenzima de la SRD5A, la de tipo 3, que se expresa en células cancerosas. Se ha demostrado que SRD5A3 está sobreexpresada en varios cánceres con mal pronóstico. En este artículo se revisaron también algunas de las moléculas esteroidales y no esteroidales reconocidas como bloqueadores eficaces de la actividad de esta enzima, logrando mejorar las terapias para la hipertrofia prostática benigna, la calvicie androgénica y el cáncer de la próstata. En conclusión, se ha reconocido que la SRD5A tiene un papel crucial en la reducción de los dobles enlaces carbono-carbono (Δ4) del anillo A del esqueleto esteroidal en los seres vivientes y que la secuencia de aminoácidos de las isoformas SRD5A1 y 2 en humanos, posee una homología con otras especies. Sin embargo, las propiedades bioquímicas y fisiológicas de la isoforma SRD5A3 no han sido tan ampliamente estudiadas. Es importante considerar la dificultad para cristalizar estas reductasas, debido a su ubicación membranal.

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Lassche, Gerben, Yuichiro Tada, Carla M. L. van Herpen, Marianne A. Jonker, Toshitaka Nagao, Takashi Saotome, Hideaki Hirai et al. "Predictive and Prognostic Biomarker Identification in a Large Cohort of Androgen Receptor-Positive Salivary Duct Carcinoma Patients Scheduled for Combined Androgen Blockade". Cancers 13, n. 14 (14 luglio 2021): 3527. http://dx.doi.org/10.3390/cancers13143527.

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Patients suffering from recurrent or metastatic (R/M) salivary duct carcinoma (SDC) are often treated with combined androgen blockade (CAB). However, CAB frequently fails, resulting in a worse prognosis. Therefore, biomarkers that can predict treatment failure are urgently needed. mRNA from 76 R/M androgen receptor (AR)-positive SDC patients treated with leuprorelin acetate combined with bicalutamide was extracted from pre-treatment tumor specimens. AR, Notch, MAPK, TGFβ, estrogen receptor (ER), Hedgehog (HH), and PI3K signaling pathway activity scores (PAS) were determined based on the expression levels of target genes. Additionally, 5-alpha reductase type 1 (SRD5A1) expression was determined. These markers were related to clinical benefit (complete/partial response or stable disease ≥6 months) and progression-free and overall survival (PFS/OS). SRD5A1 expression had the highest general predictive value for clinical benefit and positive predictive value (PPV: 85.7%). AR PAS had the highest negative predictive value (NPV: 93.3%). The fitting of a multivariable model led to the identification of SRD5A1, TGFβ, and Notch PAS as the most predictive combination. High AR, high Notch, high ER, low HH PAS, and high SRD5A1 expression were also of prognostic importance regarding PFS and SRD5A1 expression levels for OS. AR, Notch PAS, and SRD5A1 expression have the potential to predict the clinical benefit of CAB treatment in SDC patients. SRD5A1 expression can identify patients that will and AR PAS patients that will not experience clinical benefit (85.7% and 93.3% for PPV and NPV, respectively). The predictive potential of SRD5A1 expression forms a rational basis for including SRD5A1-inhibitors in SDC patients’ treatment.

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Wako, K., T. Kawasaki, K. Yamana, K. Suzuki, S. Jiang, H. Umezu, T. Nishiyama et al. "Expression of androgen receptor through androgen-converting enzymes is associated with biological aggressiveness in prostate cancer". Journal of Clinical Pathology 61, n. 4 (24 agosto 2007): 448–54. http://dx.doi.org/10.1136/jcp.2007.050906.

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Aims:The association between the expression of androgen receptor (AR) or androgen-converting enzymes and malignant potential in prostate cancer (PCa) was examined.Methods:PCa specimens from 44 cases of stage II, 10 cases of stage III, four cases of stage IV and two recurrent cases were semi-quantitatively studied with immunohistochemistry for AR and androgen-converting enzymes.Results:The expression scores for AR, 5α-reductase type 1 (SRD5A1), 5α-reductase type 2 (SRD5A2), and aldo-keto reductase family 1 member C3 (AKR1C3) in the metastatic lesion of stage IV or recurrent cancer (n = 6) were 284.2 (30.1), 300 (0.0), 279.2 (51) and 254.2 (74.9), respectively; these scores were significantly higher than the respective scores of 121.8 (82.1), 135.1 (59.7), 167.0 (66.4) and 150.5 (62.8) for stage II and III cancer (n = 54) (p<0.001, p<0.001, p = 0.002 and p = 0.018, respectively). The expression scores for AR and SRD5A1 in stage II and III cancer with Gleason score 7 (n = 19) were 128.7 (72.3) and 150.5 (52.9); these were significantly higher than the scores of 78.8 (67.2) and 100.0 (39.6), respectively, for cancers with a Gleason score of ⩽6 (n = 20) (p = 0.032 and p = 0.002, respectively). The expression scores for AR, SRD5A1 and AKR1C3 in stage II and III cancer with primary Gleason pattern ⩾4 (n = 21) were 158.1 (84.3), 158.3 (61.1) and 173.8 (64.8); these were significantly higher than the scores of 98.6 (72.8), 120.3 (54.7) and 135.6 (57.6), respectively, for cancers with primary Gleason pattern ⩽3 (n = 33) (p = 0.011, p = 0.026 and p = 0.034, respectively). Within Gleason score 9 cancer, the expression scores for AR and SRD5A1 in the primary lesion of stage IV (n = 3) were 276.7 (5.8) and 283.3 (28.9); these scores were significantly higher than the scores of 182.1 (86.0) and 140.0 (56.6), respectively, for stage II and III cancer (n = 7) (p = 0.027 and p = 0.001, respectively).Conclusions:Both AR and androgen-converting enzymes were upregulated in high-grade or advanced PCa.

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Lassche, Gerben, Yuichiro Tada, Carla M. L. Van Herpen, Marianne A. Jonker, Diederick Keizer, Wim Verhaegh, Toshitaka Nagao et al. "Predictive and prognostic biomarker identification in a large cohort of androgen receptor-positive salivary duct carcinoma patients scheduled for combined androgen blockade." Journal of Clinical Oncology 39, n. 15_suppl (20 maggio 2021): 6071. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.6071.

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6071 Background: Patients suffering from recurrent or metastatic (R/M) salivary duct carcinoma (SDC) are often treated with combined androgen blockade (CAB). This treatment however frequently fails (response rates: 18-53%), resulting in a worse prognosis. Therefore, biomarkers that have prognostic value and can predict treatment response are urgently needed. Methods: mRNA from 77 R/M androgen receptor (AR) positive SDC patients treated with leuprorelin acetate combined with bicalutamide was extracted from pre-treatment tumor specimens. AR, Notch, Mitogen-Activated Protein Kinase (MAPK), Transforming Growth Factor beta (TGFβ), Estrogen Receptor (ER), Hedgehog (HH) and the Phosphoinositide 3-Kinase (PI3K) signaling pathway activities were calculated based on expression levels of relevant target genes. Besides this, 5-alpha reductase type 1 ( SRD5A1) expression and Human Epidermal growth factor Receptor 2 (HER2) status were determined. Clinical benefit was defined as complete or partial response or stable disease ≥6 months. Results: Of the 7 signaling pathways, AR pathway activity was the best predictor of clinical benefit (AUC 0.67, 95%-CI 0.54-0.80). At a threshold of 47.8, 21% of the patients tested negative, with a negative predictive value of 93%. SRD5A1 expression outperformed the signaling pathways regarding predictive value (AUC 0.78, 95%-CI 0.67-0.88). Fitting of a multivariable model led to the identification of SRD5A1, Notch and TGFβ as most predictive combination (AUC 0.82, 95%-CI 0.72-0.91). AR, Notch, HH and SRD5A1 were also of prognostic importance regarding progression free survival and SRD5A1 expression levels also for overall survival (median of 175.0 weeks for high versus 96.7 weeks for low expression). Conclusions: Our study revealed predictive and/or prognostic value of AR, HH, Notch and TGFβ signaling activities and SRD5A1 expression in SDC patients treated with CAB. AR pathway activity can be used for identifying non-responders. Further clinical validation is required before implementation of these biomarkers in clinical practice. The observed role of SRD5A1 expression in CAB response forms a rational basis for including SRD5A1-inhibitors in the treatment of SDC patients.[Table: see text]

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Muangsanguan, Anurak, Warintorn Ruksiriwanich, Chaiwat Arjin, Sansanee Jamjod, Chanakan Prom-u-Thai, Pensak Jantrawut, Pornchai Rachtanapun et al. "Comparison of In Vitro Hair Growth Promotion and Anti-Hair Loss Potential of Thai Rice By-Product from Oryza sativa L. cv. Buebang 3 CMU and Sanpatong". Plants 13, n. 21 (1 novembre 2024): 3079. http://dx.doi.org/10.3390/plants13213079.

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The bioactive compounds in herbal extracts may provide effective hair loss treatments with fewer side effects compared to synthetic medicines. This study evaluated the effects of Buebang 3 CMU and Sanpatong rice bran extracts, macerated with dichloromethane or 95% ethanol, on hair growth promotion and hair loss prevention. Overall, Buebang 3 CMU extracts contained significantly higher levels of bioactive compounds, including γ-oryzanol, tocopherols, and various polyphenols such as phytic acid, ferulic acid, and chlorogenic acid, compared to Sanpatong extracts. Additionally, ethanolic extracts demonstrated greater bioactive content and antioxidant activities than those extracted with dichloromethane. These compounds enhanced the proliferation of human hair follicle dermal papilla cells (HFDPCs) by 124.28 ± 1.08% (p < 0.05) and modulated anti-inflammatory pathways by reducing nitrite production to 3.20 ± 0.36 µM (p < 0.05). Key hair growth signaling pathways, including Wnt/β-catenin (CTNNB1), Sonic Hedgehog (SHH, SMO, GLI1), and vascular endothelial growth factor (VEGF), were activated by approximately 1.5-fold to 2.5-fold compared to minoxidil. Also, in both human prostate cancer (DU-145) and HFDPC cells, the ethanolic Buebang 3 CMU extract (Et-BB3-CMU) suppressed SRD5A1, SRD5A2, and SRD5A3 expression—key pathways in hair loss—by 2-fold and 1.5-fold more than minoxidil and finasteride, respectively. These findings suggest that Et-BB3-CMU holds promise for promoting hair growth and preventing hair loss.

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Bamodu, Oluwaseun Adebayo, Kai-Yi Tzou, Chia-Da Lin, Su-Wei Hu, Yuan-Hung Wang, Wen-Ling Wu, Kuan-Chou Chen e Chia-Chang Wu. "Differential but Concerted Expression of HSD17B2, HSD17B3, SHBG and SRD5A1 Testosterone Tetrad Modulate Therapy Response and Susceptibility to Disease Relapse in Patients with Prostate Cancer". Cancers 13, n. 14 (12 luglio 2021): 3478. http://dx.doi.org/10.3390/cancers13143478.

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Background: Testosterone plays a critical role in prostate development and pathology. However, the impact of the molecular interplay between testosterone-associated genes on therapy response and susceptibility to disease relapse in PCa patients remains underexplored. Objective: This study investigated the role of dysregulated or aberrantly expressed testosterone-associated genes in the enhanced dissemination, phenoconversion, and therapy response of treatment-resistant advanced or recurrent PCa. Methods: Employing a combination of multi-omics big data analyses, in vitro, ex vivo, and in vivo assays, we assessed the probable roles of HSD17B2, HSD17B3, SHBG, and SRD5A1-mediated testosterone metabolism in the progression, therapy response, and prognosis of advanced or castration-resistant PCa (CRPC). Results: Our bioinformatics-aided gene expression profiling and immunohistochemical staining showed that the aberrant expression of the HSD17B2, HSD17B3, SHBG, and SRD5A1 testosterone metabolic tetrad characterize androgen-driven PCa and is associated with disease progression. Reanalysis of the TCGA PRAD cohort (n = 497) showed that patients with SRD5A1-dominant high expression of the tetrad exhibited worse mid-term to long-term (≥5 years) overall survival, with a profoundly shorter time to recurrence, compared to those with low expression. More so, we observed a strong association between enhanced HSD17B2/SRD5A1 signaling and metastasis to distant lymph nodes (M1a) and bones (M1b), while upregulated HSD17B3/SHBG signaling correlated more with negative metastasis (M0) status. Interestingly, increased SHBG/SRD5A1 ratio was associated with metastasis to distant organs (M1c), while elevated SRD5A1/SHBG ratio was associated with positive biochemical recurrence (BCR) status, and shorter time to BCR. Molecular enrichment and protein–protein connectivity network analyses showed that the androgenic tetrad regulates testosterone metabolism and cross-talks with modulators of drug response, effectors of cell cycle progression, proliferation or cell motility, and activators/mediators of cancer stemness. Moreover, of clinical relevance, SHBG ectopic expression (SHBG_OE) or SRD5A1 knockout (sgSRD5A1) induced the acquisition of spindle fibroblastoid morphology by the round/polygonal metastatic PC-3 and LNCaP cells, attenuated their migration and invasion capability, and significantly suppressed their ability to form primary or secondary tumorspheres, with concomitant downregulation of stemness KLF4, OCT3/4, and drug resistance ABCC1, ABCB1 proteins expression levels. We also showed that metronomic dutasteride synergistically enhanced the anticancer effect of low-dose docetaxel, in vitro, and in vivo. Conclusion: These data provide proof of concept that re-reprogramming of testosterone metabolism through “SRD5A1 withdrawal” or “SHBG induction” is a workable therapeutic strategy for shutting down androgen-driven oncogenic signals, reversing treatment resistance, and repressing the metastatic/recurrent phenotypes of patients with PCa.

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Valenzuela Scheker, Evana, Amita Kathuria, Ashwini Esnakula, Hironobu Sasano, Yuto Yamazaki, Sergei Tevosian, Richard J. Auchus, Hans K. Ghayee e Gauri Dhir. "Expression of Key Androgen-Activating Enzymes in Ovarian Steroid Cell Tumor, Not Otherwise Specified". Journal of Investigative Medicine High Impact Case Reports 8 (gennaio 2020): 232470962093341. http://dx.doi.org/10.1177/2324709620933416.

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To characterize the expression of steroidogenic enzymes implicated in the development of ovarian steroid cell tumors, not otherwise specified (SCT-NOS). We present 4 ovarian SCT-NOS evaluated by immunohistochemical staining of steroidogenic enzymes as an approach to define this entity pathologically. All 4 ovarian SCT-NOS showed increased expression for cholesterol side-chain cleavage enzyme (CYP11A1), 17α-hydroxylase (CYP17A1), 17β-hydroxysteroid dehydrogenase 1 (HSD17B1), aldo-ketoreductase type 1 C3 (AKR1C3), 3β-hydroxysteroid dehydrogenase 2 (HSD3B2), 5α-reductase type 2 (SRD5A2), steroid sulfatase (SULT2A1), estrogen sulfotransferase (EST), and aromatase (CYP19A1). Expression was negative for 21-hydroxylase (CYP21A2) and 17β-hydroxysteroid dehydrogenase 2 (HSD17B2). 17β-hydroxysteroid dehydrogenase 3 (HSD17B3) and 5α-reductase type 1 (SRD5A1) showed variable expression. Our analysis reveals a novel finding of increased expression of AKR1C3, HSD17B1, SRD5A2, SULT2A1, and EST in ovarian SCT-NOS, which is clinically associated with androgen excess and virilization. Further studies are needed to validate these enzymes as new markers in the evaluation of hyperandrogenic ovarian conditions.

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Fischer, Alexandra, Sonja Gaedicke, Jan Frank, Frank Döring e Gerald Rimbach. "Dietary vitamin E deficiency does not affect global and specific DNA methylation patterns in rat liver". British Journal of Nutrition 104, n. 7 (7 maggio 2010): 935–40. http://dx.doi.org/10.1017/s0007114510001649.

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The aim of the present study was to determine the effects of a 6-month dietary vitamin E (VE) deficiency on DNA methylation and gene expression in rat liver. Two enzymes, 5-α-steroid reductase type 1 (SRD5A1) and the regulatory subunit of γ-glutamylcysteinyl synthetase (GCLM), which are differentially expressed on the mRNA level, were analysed for promoter methylation in putative cytosine-phospho-guanine (CpG) island regions located at the 5′ end using base-specific cleavage and matrix-assisted laser desorption ionisation time-of-flight MS. A twofold increase in the mRNA level of SRD5A1 gene and a twofold decrease in the mRNA level of GCLM gene in VE-deficient animals were not associated with different CpG methylation of the analysed promoter region. Furthermore, global DNA methylation was not significantly different in these two groups. Thus, the present results indicate that the VE-induced regulation of SRD5A1 and GCLM in rat liver is not directly mediated by changes in promoter DNA methylation.

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Muangsanguan, Anurak, Pichchapa Linsaenkart, Tanakarn Chaitep, Jiraporn Sangta, Sarana Rose Sommano, Korawan Sringarm, Chaiwat Arjin et al. "Hair Growth Promotion and Anti-Hair Loss Effects of By-Products Arabica Coffee Pulp Extracts Using Supercritical Fluid Extraction". Foods 12, n. 22 (13 novembre 2023): 4116. http://dx.doi.org/10.3390/foods12224116.

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Coffee has been a common ingredient in many traditional hair loss remedies, but limited scientific evidence supports its use, particularly in coffee pulp. Androgenetic alopecia (AGA) is caused by androgens, inflammation, and oxidative stress. In the present study, supercritical fluid extraction (SFE) was used under various conditions to obtain six coffee pulp extracts. The SFE-4 extract, using 50% (v/v) ethanol as a co-solvent at conditions of 100 °C and 500 bars for 30 min, exhibited the highest phenolic, flavonoid, and caffeine contents. Additionally, the SFE-4 extract increased the migration and cell proliferation of HFDPCs (human hair follicle dermal papilla cells), which control hair cycle regulation, and had scavenging effects on ABTS and DPPH radicals. Additionally, the SFE-4 extract showed potassium ion channel opener activity in HFDPCs, as well as a stimulation effect on the enzyme matrix metalloproteinase-2 (MMP-2) (28.53 ± 1.08% of control), which may be related to the vascular endothelial growth factor (VEGF) gene upregulation. In human prostate cancer cells (DU-145) and HFDPC cells, the SFE-4 extract significantly decreased the expression of SRD5A1, SRD5A2, and SRD5A3, an essential pathway involved in AGA. Hair growth factor genes in the Wnt/-catenin (CTNNB1) and Sonic Hedgehog (SHH, SMO, and GLI1) pathways could be significantly activated by the SFE-4 extract. These results imply that employing SFE in coffee pulp extraction could help AGA treatment by preventing hair loss and promoting hair growth pathways. This would help small coffee producers gain economic empowerment and ensure the long-term sustainability of agricultural waste utilization.

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Caglayan, A. Okay, Munis Dundar, Fatih Tanriverdi, Nuran A. Baysal, Kursad Unluhizarci, Yusuf Ozkul, Murat Borlu, Cem Batukan e Fahrettin Kelestimur. "Idiopathic hirsutism: local and peripheral expression of aromatase (CYP19A) and 5α-reductase genes (SRD5A1 and SRD5A2)". Fertility and Sterility 96, n. 2 (agosto 2011): 479–82. http://dx.doi.org/10.1016/j.fertnstert.2011.05.040.

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Applegate, Catherine, Matthew Lowerison, Emma Hambley, Pengfei Song e John Erdman. "Dietary Tomato Inhibits Tumor Angiogenesis in the TRAMP Model of Prostate Cancer but Is Not Protective With a Western-Style Diet". Current Developments in Nutrition 5, Supplement_2 (giugno 2021): 260. http://dx.doi.org/10.1093/cdn/nzab036_002.

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Abstract Objectives The objective of this study was to investigate the interplay between tomato powder (TP), incorporated into control (CON) and obesogenic (OB) diets, and PCa tumor growth and blood perfusion over time in a transgenic model of PCa. We hypothesized that TP would be protective against PCa growth. Methods Diets (either CON [17.2% kcal from fat] or OB [44.6% kcal from fat] both with and without 10% TP) were fed to transgenic adenocarcinoma of the mouse prostate (TRAMP) mice (n = 5/dietary group) from weaning. Tumor growth was monitored by weekly ultrasound scanning, at which time novel ultrasound microvessel images (UMI) were captured to quantitatively measure tumor blood perfusion over time. Animals were euthanized after 5 weeks of tumor growth, and tissues were collected for measurement of protein (HIF-1α, TNFα) and gene (ar, srd5a1, srd5a2) expression. Data were analyzed to determine differences between CON diets (without TP + with 10% TP) and OB diets (without TP + with 10% TP) and to evaluate the impact of 10% TP on outcome measures both independent of TP (No TP vs. TP) as well as within CON and OB diets (interaction effect of diet*TP) by mixed model ANCOVA with body weight as a covariate. Results UMI results showed good agreement with gold-standard immunohistochemistry quantification of endothelial cell density, indicating that this technique can be applied to non-invasively and longitudinally monitor tumor blood perfusion in vivo. Greater body weight (P = 0.029) and OB diets (P = 0.008) were associated with earlier age at tumor detection, and greater body weight was positively associated with tumor growth (P = 0.001). TP significantly inhibited prostate tumor angiogenesis (P = 0.043), but this inhibition differentially affected measured outcomes depending on CON or OB diets. TP led to reduced tumor growth (P = 0.004), intratumoral inflammation (TNFα; P = 0.019), and intratumoral androgen-regulated gene expression (srd5a1, srd5a2; P = 0.030 and P = 0.016, respectively) when incorporated with the CON diet but greater tumor growth and intratumoral gene expression when incorporated with the OB diet. Conclusions Results from this study show that protective benefits from dietary tomato are lost, or may become deleterious, when combined with a Western-style diet. Funding Sources CA was supported by the NIH NIBIB. MRL and PS were partially supported by NIH NCI.

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Zhou, Zhifeng, e Phyllis W. Speiser. "Regulation of HSD17B1 and SRD5A1 in Lymphocytes". Molecular Genetics and Metabolism 68, n. 3 (novembre 1999): 410–17. http://dx.doi.org/10.1006/mgme.1999.2898.

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Klotsman, M., C. R. Weinberg, K. Davis, C. G. Binnie e K. E. Hartmann. "A case-based evaluation of SRD5A1, SRD5A2, AR, and ADRA1A as candidate genes for severity of BPH". Pharmacogenomics Journal 4, n. 4 (11 maggio 2004): 251–59. http://dx.doi.org/10.1038/sj.tpj.6500248.

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Barnard, Lise, Nikolaos Nikolaou, Carla Louw, Lina Schiffer, Hylton Gibson, Lorna C. Gilligan, Elena Gangitano et al. "The A-ring reduction of 11-ketotestosterone is efficiently catalysed by AKR1D1 and SRD5A2 but not SRD5A1". Journal of Steroid Biochemistry and Molecular Biology 202 (settembre 2020): 105724. http://dx.doi.org/10.1016/j.jsbmb.2020.105724.

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Mitsiades, N., N. Schultz, B. S. Taylor, H. Hieronymus, J. Satagopan, P. T. Scardino, V. E. Reuter, C. Sander, C. Sawyers e H. I. Scher. "Increased expression of androgen receptor (AR) and enzymes involved in androgen synthesis in metastatic prostate cancer: Targets for novel personalized therapies". Journal of Clinical Oncology 27, n. 15_suppl (20 maggio 2009): 5002. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.5002.

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Abstract (sommario):

5002 Background: Androgen receptor (AR) signaling remains active in castration-resistant prostate cancer (CRPC) despite castrate levels of circulating androgens. This is indicated by continuous expression of androgen-responsive genes and is due to mechanisms that include: increased AR expression; AR mutations allowing promiscuous activation by alternative ligands; and increased intratumoral androgen levels, resulting from in situ steroidogenesis. Methods: Gene expression profiles of 30 normal prostate tissue samples, 131 primary prostate carcinomas (PCas) and 16 metastatic PCas, generated using Affymetrix Exon arrays, were interrogated for levels of 40 mRNAs encoding AR, SHBG, 28 enzymes involved in androgen synthesis and 10 enzymes involved in androgen inactivation. For individual tumors, a transcript was considered to be overexpressed or underexpressed when its levels were >2 SDs higher or lower, respectively, than its average levels in normal tissue. Results: Metastatic PCas expressed higher average transcript levels for AR and several steroidogenic enzymes, including SRD5A1 and SRD5A3, than primary PCas and normal prostate tissue. Expression of SRD5A2, CYP3A4, CYP3A5, and CYP3A7 mRNAs was decreased both in primary and metastatic tumors compared to normal prostate tissue. In analysis involving AR and 28 steroidogenic transcripts in individual tumors, all (16/16) metastatic PCas overexpressed at least one transcript (range: 2–14, median: 5 transcripts) compared to normal tissue, while 100/131 (76%) primary PCas overexpressed at least one transcript (range: 2–16, median: 2). Conclusions: Metastatic PCas overexpress AR and several steroidogenic enzymes, while they express lower levels of the androgen-inactivating enzymes CYP3A4, CYP3A5, and CYP3A7. These data highlight the role of AR and the androgen synthetic pathway as a therapeutic target in CRPC. Novel antiandrogens (MDV3100) and CYP17 inhibitors (abiraterone) are already in clinical trials in CRPC. Overexpression of AR or steroidogenic enzymes may serve as a biomarker (e.g. by detection via RT-PCR in circulating tumor cells) to predict for sensitivity to these agents and guide patient selection for participation in clinical trials. No significant financial relationships to disclose.

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Cabeza, Marisa, Luis A. Menes, Evelyn Fuentes, Iván Bahena e Yvonne Heuze. "Novel type 1 5a-reductase Inhibitors with Antiproliferative Potential on LNCaP cells". Oriental Journal Of Chemistry 39, n. 3 (30 giugno 2023): 523–32. http://dx.doi.org/10.13005/ojc/390301.

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This study demonstrated the antiproliferative potential of several dehydroepiandrosterone derivatives 2a-b, 3a-f, and 4a-f in LNCaP cells. LNCaP cells were cultured in the presence of the vehicle, dihydrotestosterone, or testosterone plus 2a-b, 3a-f, 4a-f, or finasteride. At 24 h the 3-(4,5-dimethylthiazol-2-yl)-2,5-di phenyltetrazolium bromide-test was performed to determine cell proliferation. In addition, the kinetic of SRD5A1 in these cells was studied in the presence or absence of different concentrations of 2a. Testosterone and dihydrotestosterone increased the proliferation of LNCaP compared to the vehicle-treated cells. Furthermore, steroids 2a-b, 3a-f, and 4a-f decreased the number of viable cells compared to testosterone treatment. However, finasteride did not affect viability. LNCaP cells converted radiolabeled testosterone into dihydrotestosterone. This conversion was inhibited by high concentrations of 2a, while at a pM concentration, the conversion increased slightly, suggesting the presence of allosteric sites in SRD5A1. In conclusion, the three series of derivatives of dehydroepiandrosterone significantly decreased the number of viable LNCaP cells, therefore, showing therapeutic potential to treat metastatic prostate cancer.

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Ruksiriwanich, Warintorn, Chiranan Khantham, Anurak Muangsanguan, Chuda Chittasupho, Pornchai Rachtanapun, Kittisak Jantanasakulwong, Yuthana Phimolsiripol et al. "Phytochemical Constitution, Anti-Inflammation, Anti-Androgen, and Hair Growth-Promoting Potential of Shallot (Allium ascalonicum L.) Extract". Plants 11, n. 11 (2 giugno 2022): 1499. http://dx.doi.org/10.3390/plants11111499.

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Abstract (sommario):

In Thai folklore wisdom, shallot (Allium ascalonicum L.) was applied as a traditional herbal medicine for hair growth promotion with no scientific evidence. Androgenetic alopecia (AGA) is a progressive hair loss caused by multiple factors, including androgen hormones, inflammation, and oxidative stress. Conventional medicines (finasteride, dutasteride, corticosteroids, and minoxidil) have been used with limited therapeutic efficacy and unpleasant side effects. In this study, we aimed to give the first estimation of bioactive compounds in shallot extract and evaluate the hair growth-promoting activities regarding anti-inflammatory and gene expression modulation involving androgen, Wnt/β-catenin, sonic hedgehog, and angiogenesis pathways. The results reveal that phenolic compounds (quercetin, rosmarinic, and p-coumaric acids) are the major constituents of the methanolic shallot extract. Compared with the lipopolysaccharide-stimulated control group (2.68 ± 0.13 µM), nitric oxide production was remarkably diminished by shallot extract (0.55 ± 0.06 µM). Shallot extract improves hair growth promotion activity, as reflected by the downregulation of the androgen gene expression (SRD5A1 and SRD5A2) and the upregulation of the genes associated with Wnt/β-catenin (CTNNB1), sonic hedgehog (SHH, SMO, and GIL1), and angiogenesis (VEGF) pathways. These findings disclose the new insights of shallot extract on hair growth promotions. Shallot extract could be further developed as nutraceutical, nutricosmetic, and cosmeceutical preparations for AGA treatment.

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Ramos, Luis, Bertha Chávez e Felipe Vilchis. "Cloning and differential expression of steroid 5α-reductase type 1 (Srd5a1) and type 2 (Srd5a2) from the Harderian glands of hamsters". General and Comparative Endocrinology 166, n. 2 (aprile 2010): 388–95. http://dx.doi.org/10.1016/j.ygcen.2009.12.010.

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Graupp, M., E. Wehr, N. Schweighofer, T. R. Pieber e B. Obermayer-Pietsch. "Association of genetic variants in the two isoforms of 5α-reductase, SRD5A1 and SRD5A2, in lean patients with polycystic ovary syndrome". European Journal of Obstetrics & Gynecology and Reproductive Biology 157, n. 2 (agosto 2011): 175–79. http://dx.doi.org/10.1016/j.ejogrb.2011.03.026.

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Barresi, Vincenza, Salvatore S. Signorelli, Nicolò Musso, Massimiliano Anzaldi, Valerio Fiore, Mario Alberghina e Daniele Filippo Condorelli. "ICAM-1 and SRD5A1 gene polymorphisms in symptomatic peripheral artery disease". Vascular Medicine 19, n. 3 (30 maggio 2014): 175–81. http://dx.doi.org/10.1177/1358863x14532705.

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Taheri, Serpil, Gokmen Zararsiz, Sulbiye Karaburgu, Murat Borlu, Mahmut Tuncay Ozgun, Zuleyha Karaca, Fatih Tanriverdi, Munis Dundar, Fahrettin Kelestimur e Kursad Unluhizarci. "Is idiopathic hirsutism (IH) really idiopathic? mRNA expressions of skin steroidogenic enzymes in women with IH". European Journal of Endocrinology 173, n. 4 (ottobre 2015): 447–54. http://dx.doi.org/10.1530/eje-15-0460.

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Abstract (sommario):

ObjectiveHirsutism results from hyperandrogenemia and/or exaggerated androgen responsiveness. Among various causes of hirsutism, some patients do not exhibit androgen excess which is called idiopathic hirsutism (IH). The pathogenesis of IH could not so far be clearly established.DesignTo investigate the mRNA expression of aromatase enzyme and the other enzymes having functional roles in the steroidogenic pathway, in freshly obtained skin tissue from subumbilical skin and the arm of the patients with IH and healthy women.MethodsTwenty-one women with IH and 15 healthy women were included in the study. We aimed to determine mRNA expressions of genes associated with local androgen synthesis and metabolism (CYP11A1, STS, CYP19A1, SRD5A1, SRD5A2, HSD3B1, AR, COMT, ESR1, ESR2, HSD3B2, CYP17A1, SULT2A1, SULT1E1, HSD17B2, IL6, TGFB1, TNFA) from skin biopsy and blood samples of patients with IH and the data compared with healthy subjects.ResultsPatients with IH exhibit significantly lower interleukin 6 (IL6) mRNA expression and higher steroid sulphatase (STS) and hydroxysteroid (17beta) dehydrogenase 2 (HSD17B2), gene mRNA expression, respectively, in the subumbilical region skin biopsies. Similarly, patients with IH exhibit significantly lowerIL6mRNA expression and higherSTSandHSD17B2gene mRNA expression, respectively, in the arm skin compared to healthy women's subumbilical region.ConclusionsIn both arm and subumbilical skin biopsy of patients with IH, we observed an up-regulation ofHSD17B2andSTS, decreasedIL6mRNA expression, probably determining an increase in the local amount of active androgens, which could then be used as substrate for other androgen metabolic routes.

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Rył, Aleksandra, Iwona Rotter, Anna Grzywacz, Iwona Małecka, Karolina Skonieczna-Żydecka, Katarzyna Grzesiak, Marcin Słojewski et al. "Molecular Analysis of the SRD5A1 and SRD5A2 Genes in Patients with Benign Prostatic Hyperplasia with Regard to Metabolic Parameters and Selected Hormone Levels". International Journal of Environmental Research and Public Health 14, n. 11 (30 ottobre 2017): 1318. http://dx.doi.org/10.3390/ijerph14111318.

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Gu, Xin, Rong Na, Tao Huang, Li Wang, Sha Tao, Lu Tian, Zhuo Chen et al. "SRD5A1 and SRD5A2 are Associated with Treatment for Benign Prostatic Hyperplasia with the Combination of 5α-Reductase Inhibitors and α-Adrenergic Receptor Antagonists". Journal of Urology 190, n. 2 (agosto 2013): 615–19. http://dx.doi.org/10.1016/j.juro.2013.03.024.

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Ha, Mei, Pei Zhang, Lianbing Li e Changjiang Liu. "Triclosan Suppresses Testicular Steroidogenesis via the miR-6321/JNK/ Nur77 Cascade". Cellular Physiology and Biochemistry 50, n. 6 (2018): 2029–45. http://dx.doi.org/10.1159/000495049.

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Abstract (sommario):

Background/Aims: Triclosan (TCS), a broad-spectrum antibacterial and antifungal compound and an endocrine disruptor, has anti-androgenic properties and could adversely affect male reproduction and fertility. Methods: To elucidate the underlying roles of miRNAs and the MAPK pathway in TCS-mediated repression of testicular steroidogenesis, Sprague-Dawley male rats were dosed daily with TCS for 31 days, and TM3 cells were exposed to TCS for 24 h after the pretreatments with the activator of JNK, Nur77 siRNA, or recombinant lentivirus vector for Nur77. Tissues and/or cells were analyzed by several techniques including transmission electron microscopy, lentivirus production, overexpression, gene silencing, luciferase reporter assay, chromatin immunoprecipitation, western blot, and real-time PCR. Results: TCS caused histopathologic alterations in the testis and reduced plasma LH and testicular testosterone. TCS induced miR-6321 expression, which in turn depressed its target gene, Map3k1. The inhibition of Map3k1 subsequently inactivated its downstream JNK/c-Jun pathway. ChIP and qPCR assays confirmed that c-Jun directly bound to the Nur77 DNA promoter regions to regulate Nur77 expression. The knockdown and overexpression of Nur77 demonstrated that the JNK/c-Jun-mediated decline in the transcription and translation of Nur77 resulted in the depression of steroidogenic proteins including SRB1, StAR, and 3β-HSD. Intriguingly, the protein expressions of 5α-Reductases (SRD5A1 and SRD5A2) were also downregulated after TCS exposure. Conclusion: Taken together, the miR-6321/Map3k1-regulated JNK/c-Jun/ Nur77 cascade contributes to TCS-caused suppression of testicular steroidogenesis, and the decrease in 5α-Reductase expressions may be the compensatory mechanism.

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Adams, Marlene, e Susan McCrone. "SRD5A1 Genotype Frequency Differences in Women with Mild versus Severe Premenstrual Symptoms". Issues in Mental Health Nursing 33, n. 2 (25 gennaio 2012): 101–8. http://dx.doi.org/10.3109/01612840.2011.625514.

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Wu, X. W., K.-F. P. Chiu e C.-F. Ng. "Mechanism of IL-6/STAT3 regulation of SRD5A1 in prostate cancer cells". European Urology Open Science 57 (novembre 2023): S380. http://dx.doi.org/10.1016/s2666-1683(23)01570-7.

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El-Sheikh Ali, H., E. L. Legacki, K. E. Scoggin, S. C. Loux, P. Dini, A. Esteller-Vico, A. J. Conley, S. D. Stanley e B. A. Ball. "Steroid synthesis and metabolism in the equine placenta during placentitis". Reproduction 159, n. 3 (marzo 2020): 289–302. http://dx.doi.org/10.1530/rep-19-0420.

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Abstract (sommario):

Equine placentitis is associated with alterations in maternal peripheral steroid concentrations, which could negatively affect pregnancy outcome. This study aimed to elucidate the molecular mechanisms related to steroidogenesis and steroid-receptor signaling in the equine placenta during acute placentitis. Chorioallantois (CA) and endometrial (EN) samples were collected from mares with experimentally induced placentitis (n = 4) and un-inoculated gestationally age-matched mares (control group; n = 4). The mRNA expression of genes coding for steroidogenic enzymes (3βHSD, CYP11A1, CYP17A1, CYP19A1, SRD5A1, and AKR1C23) was evaluated using qRT-PCR. The concentration of these enzyme-dependent steroids (P5, P4, 5αDHP, 3αDHP, 20αDHP, 3β-20αDHP, 17OH-P, DHEA, A4, and estrone) was assessed using liquid chromatography-tandem mass spectrometry in both maternal circulation and placental tissue. Both SRD5A1 and AKR1C23, which encode for the key progesterone metabolizing enzymes, were downregulated (P < 0.05) in CA from the placentitis group compared to controls, and this downregulation was associated with a decline in tissue concentrations of 5αDHP (P < 0.05), 3αDHP (P < 0.05), and 3β-20αDHP (P = 0.052). In the EN, AKR1C23 was also downregulated in the placentitis group compared to controls, and this downregulation was associated with a decline in EN concentrations of 3αDHP (P < 0.01) and 20αDHP (P < 0.05). Moreover, CA expression of CYP19A1 tended to be lower in the placentitis group, and this reduction was associated with lower (P = 0.057) concentrations of estrone in CA. Moreover, ESR1 (steroid receptors) gene expression was downregulated (P = 0.057) in CA from placentitis mares. In conclusion, acute equine placentitis is associated with a local withdrawal of progestins in the placenta and tended to be accompanied with estrogen withdrawals in CA.

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Hazra, Rasmani, Mark Jimenez, Reena Desai, David J. Handelsman e Charles M. Allan. "Sertoli Cell Androgen Receptor Expression Regulates Temporal Fetal and Adult Leydig Cell Differentiation, Function, and Population Size". Endocrinology 154, n. 9 (13 giugno 2013): 3410–22. http://dx.doi.org/10.1210/en.2012-2273.

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Abstract (sommario):

We recently created a mouse model displaying precocious Sertoli cell (SC) and spermatogenic development induced by SC-specific transgenic androgen receptor expression (TgSCAR). Here we reveal that TgSCAR regulates the development, function, and absolute number of Leydig cells (LCs). Total fetal and adult type LC numbers were reduced in postnatal and adult TgSCAR vs control testes, despite normal circulating LH levels. Normal LC to SC ratios found in TgSCAR testes indicate that SC androgen receptor (SCAR)-mediated activity confers a quorum-dependent relationship between total SC and LC numbers. TgSCAR enhanced LC differentiation, shown by elevated ratios of advanced to immature LC types, and reduced LC proliferation in postnatal TgSCAR vs control testes. Postnatal TgSCAR testes displayed up-regulated expression of coupled ligand-receptor transcripts (Amh-Amhr2, Dhh-Ptch1, Pdgfa-Pdgfra) for potential SCAR-stimulated paracrine pathways, which may coordinate LC differentiation. Neonatal TgSCAR testes displayed normal T and dihydrotestosterone levels despite differential changes to steroidogenic gene expression, with down-regulated Star, Cyp11a1, and Cyp17a1 expression contrasting with up-regulated Hsd3b1, Hsd17b3, and Srd5a1 expression. TgSCAR males also displayed elevated postnatal and normal adult serum testosterone levels, despite reduced LC numbers. Enhanced adult-type LC steroidogenic output was revealed by increased pubertal testicular T, dihydrotestosterone, 3α-diol and 3β-diol levels per LC and up-regulated steroidogenic gene (Nr5a1, Lhr, Cyp11a1, Cyp17a1, Hsd3b6, Srd5a1) expression in pubertal or adult TgSCAR vs control males, suggesting regulatory mechanisms maintain androgen levels independently of absolute LC numbers. Our unique gain-of-function TgSCAR model has revealed that SCAR activity controls temporal LC differentiation, steroidogenic function, and population size.

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Lemus, Ana E., Juana Enríquez, Ángeles Hernández, René Santillán e Gregorio Pérez-Palacios. "Bioconversion of norethisterone, a progesterone receptor agonist into estrogen receptor agonists in osteoblastic cells". Journal of Endocrinology 200, n. 2 (10 novembre 2008): 199–206. http://dx.doi.org/10.1677/joe-08-0166.

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A number of clinical studies have demonstrated that norethisterone (NET), a potent synthetic progestin, restores postmenopausal bone loss, although its mode of action on bone cells is not fully understood, while the effect of naturally occurring progesterone in bone has remained controversial. A recent report claims that the potent effects of NET on osteoblastic cell proliferation and differentiation, mimicking the action of estrogens, are mediated by non-phenolic NET derivatives. To determine whether osteoblasts possess the enzymes required to bioconvert a progesterone receptor (PR) agonist into A-ring reduced metabolites with affinity to bind estrogen receptor (ER), we studied the in vitro metabolism of [3H]-labeled NET in cultured neonatal rat osteoblasts and the interaction of its metabolic conversion products with cytosolic –osteoblast ER, employing a competition analysis. Results indicated that NET was extensively bioconverted (36.4%) to 5α-reduced metabolites, including 5α-dihydro NET, 3α,5α-tetrahydro NET (3α,5α-NET) and 3β,5α-tetrahydro NET (3β,5α-NET), demonstrating the activities of 5α-steroid reductase and two enzymes of the aldo-keto reductases family. Expression of Srd5a1 in neonatal osteoblast was well demonstrated, whereas Srd5a2 expression was not detected. The most striking finding was that 3β,5α-NET and 3α,5α-NET were efficient competitors of [3H]-estradiol for osteoblast ER binding sites, exhibiting affinities similar to that of estradiol. The results support the concept that the interplay of 5α-steroid reductase and aldo-keto reductases in osteoblastic cells, acting as an intracrine modulator system is capable to bioconvert a PR agonist into ER agonists, offering an explanation of the molecular mechanisms NET uses to enhance osteoblastic cell activities.

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Liu, Xue, Dandan Wei, Jingjing Jiang, Xiaotian Liu, Runqi Tu, Zhicheng Luo, Yan Wang et al. "Associations of SRD5A1 gene variants and testosterone with dysglycemia: Henan Rural Cohort study". Nutrition, Metabolism and Cardiovascular Diseases 30, n. 4 (aprile 2020): 599–607. http://dx.doi.org/10.1016/j.numecd.2019.11.011.

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Gu, X., R. Na, W. Li, S. Tao, L. Tian, Z. Chen, Y. Jiao et al. "901 SRD5A1 and SRD5A2 genes are associated with the treatment for benign prostatic hyperplasia with the combination of 5α-reductase inhibitors and α-adrenergic-receptor antagonist". European Urology Supplements 12, n. 1 (marzo 2013): e901. http://dx.doi.org/10.1016/s1569-9056(13)61380-9.

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Miao, Zhuo, Min Sun, Feng Jiang, Yuanqing Yao e Yi Li. "Negative Effects of SRD5A1 on Nuclear Activity of Progesterone Receptor Isoform B in JEG3 Cells". Reproductive Sciences 23, n. 2 (4 agosto 2015): 192–99. http://dx.doi.org/10.1177/1933719115597764.

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Eminović, Izet, Mirjana Liović, Janez Preželj, Andreja Kocijančič, Damjana Rozman e Radovan Komel. "New steroid 5Α-reductase type I (SRD5A1) homologous sequences on human chromosomes 6 and 8". Pfl?gers Archiv European Journal of Physiology 442, n. 7 (1 settembre 2001): r187—r189. http://dx.doi.org/10.1007/s004240100019.

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Martin, C. S., M. Singh Kalirai, A. Crastin, D. Somma, M. Kurowska-Stolarska, J. D. Turner, L. Schiffer et al. "POS0056 GLOBAL STEROID METABOLISM IN MACROPHAGES: SHAPING INFLAMMATORY FUNCTION AND DISEASE ACTIVITY IN RHEUMATOID ARTHRITIS". Annals of the Rheumatic Diseases 81, Suppl 1 (23 maggio 2022): 244.3–244. http://dx.doi.org/10.1136/annrheumdis-2022-eular.782.

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BackgroundMacrophages are key drivers of joint destruction and disease pathophysiology in rheumatoid arthritis (RA), where their inflammatory function is influenced by steroid hormones such as androgens and glucocorticoids (GCs). Local bioavailability of these steroids is determined by both systemic adrenal/gonadal synthesis and local metabolism in peripheral target tissues. The inflammatory regulation and function of steroid hormone metabolism by key rate limiting enzymes in chronic inflammatory diseases such as RA remain poorly defined and could present new therapeutic targets.ObjectivesCharacterise regulation of global steroid metabolism in macrophages in RA and determine its contribution to androgen and GC availability, macrophage function and disease activity.MethodsBulk and single cell RNA-sequencing of FACS-sorted macrophages were analysed using previously published datasets from RA patients (27 female, 8 male)(1, 2). Gene expression of rate limiting steroid metabolism enzymes were assessed in macrophages and their subsets and correlated to clinical parameters of disease activity. Primary human monocyte-derived macrophages were polarised to non-inflammatory (M-CSF 20ng/ml) and inflammatory activated (M-CSF 20ng/ml, IFNγ 20ng/ml, TNFα 10ng/ml) subsets and treated with active or inactive metabolites of GCs (cortisol/cortisone 100nmol/l) and androgens (androstenedione/testosterone/DHEA 100nmol/l; DHT 10nmol/l). Metabolism and functional effects were assessed in primary cultures and RA synovial fluids by liquid chromatography mass spectrometry, RT-qPCR and ELISA.ResultsSignificant differentially expressed genes (DEGs) were identified in the GC and androgen metabolism pathways in synovial macrophages when stratified for high and low disease activity by DAS28-CRP. Expression of the GC-activating enzyme HSD11B1 and androgen activating enzyme SRD5A1 were significantly increased and positively correlated with disease severity. The androgen activating enzyme AKR1C3 was significantly suppressed and negatively correlated with disease severity. SRD5A1 and HSD11B1 expression were localised to S100A12pos and SPP1pos subsets associated with active RA, whilst AKR1C3 was primarily expressed by MerTKposTREM2high subsets associated with RA remission. Inflammatory activation of primary macrophages decreased AKR1C3, and increased HSD11B1 and SRD5A1 expression. This resulted in a shift in intracrine production of active GCs and androgens favouring increased levels of the active GC cortisol and the potent androgen DHT. The resulting changes in steroid ratios in inflammatory activated macrophages resulted in lower expression and release of the pro-inflammatory mediators TNFα, IL6 and IL12 indicating functional significance. In vivo, metabolic changes favouring increased GC activation and reduced androgen activation correlated with disease severity determined by DAS28-CRP.ConclusionWe have shown for the first time a role for macrophages and their tissue subsets in the inflammatory metabolism and activation of GCs and androgens in RA, which influence macrophage function and disease activity. Targeting these key metabolic pathways represents a novel route to modifying and suppressing disease activity and joint destruction in chronic polyarthritis.References[1]Zhang F, Wei K, Slowikowski K, Fonseka CY, Rao DA, Kelly S, et al. Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry. Nature Immunology. 2019;20(7):928-+.[2]Alivernini S, MacDonald L, Elmesmari A, Finlay S, Tolusso B, Gigante MR, et al. Distinct synovial tissue macrophage subsets regulate inflammation and remission in rheumatoid arthritis. Nature Medicine. 2020;26(8):1295-+.AcknowledgementsThis research was funded by the Wellcome Trust (ref: 215243/Z/19/Z)Disclosure of InterestsNone declared

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Signorelli, S. S., V. Barresi, N. Musso, M. Anzaldi, E. Croce, V. Fiore e D. F. Condorelli. "Polymorphisms of steroid 5- α- reductase type I (SRD5A1) gene are associated to peripheral arterial disease". Journal of Endocrinological Investigation 31, n. 12 (dicembre 2008): 1092–97. http://dx.doi.org/10.1007/bf03345658.

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Ogawa, Kazushige, e Takashi Tanida. "Mixed-Culture Propagation of Uterine-Tissue-Resident Macrophages and Their Expression Properties of Steroidogenic Molecules". Biomedicines 11, n. 3 (22 marzo 2023): 985. http://dx.doi.org/10.3390/biomedicines11030985.

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Tissue-resident macrophages (Mø) play tissue/organ-specific roles, and the physiological/pathological implications of uterine Mø in fertility and infertility are not yet fully understood. Herein, we report a simple propagation method for tissue-resident Mø by mixed culture with the respective tissue/organ-residing cells as the niche. We successfully propagated mouse uterine Mø by mixed culture with fibroblastic cells that exhibited properties of endometrial stromal cells. Propagated mouse uterine Mø were CD206- and arginase-1-positive; iNOS- and MHC-II-negative, indicating M2 polarization; and highly phagocytic, similar to endometrial Mø. Furthermore, uterine Mø were observed to express steroidogenic molecules including SRD5A1 and exhibited gap junction formation, likely with endometrial stromal cells. Accordingly, uterine Mø propagated by mixed culture may provide a new tool for studying immune–endocrine interactions related to fertility and infertility, particularly androgen’s intracrine actions in preparing the uterine tissue environment to support implantation and pregnancy as well as in the etiology of endometriosis.

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Redler, Silke, Rachid Tazi-Ahnini, Dmitriy Drichel, Mary P. Birch, Felix F. Brockschmidt, Kathy Dobson, Kathrin A. Giehl et al. "Selected variants of the steroid-5-alpha-reductase isoforms SRD5A1 and SRD5A2 and the sex steroid hormone receptors ESR1, ESR2 and PGR: No association with female pattern hair loss identified". Experimental Dermatology 21, n. 5 (18 aprile 2012): 390–93. http://dx.doi.org/10.1111/j.1600-0625.2012.01469.x.

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Sinreih, Maša, Maja Anko, Sven Zukunft, Jerzy Adamski e Tea Lanišnik Rižner. "Important roles of the AKR1C2 and SRD5A1 enzymes in progesterone metabolism in endometrial cancer model cell lines". Chemico-Biological Interactions 234 (giugno 2015): 297–308. http://dx.doi.org/10.1016/j.cbi.2014.11.012.

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Wu, X. W., K.-F. P. Chiu e C.-F. Ng. "Effect of obesity-associated inflammatory factor IL-6 on the vitality of prostate cancer cells via SRD5A1". European Urology Open Science 57 (novembre 2023): S379. http://dx.doi.org/10.1016/s2666-1683(23)01569-0.

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Reiter, M., M. W. Pfaffl, M. Schönfelder e H. H. D. Meyer. "Gene Expression in Hair Follicle Dermal Papilla Cells after Treatment with Stanozolol". Biomarker Insights 4 (23 dicembre 2008): BMI.S1173. http://dx.doi.org/10.4137/bmi.s1173.

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Doping with anabolic agents is a topic in sports where strength is crucial, e.g. sprinting, weight lifting and many more. Testosterone and its functional analogs are the drugs of choice taken as pills, creams, tape or injections to increase muscle mass and body performance, and to reduce body fat. Stanozolol (17β-hydroxy-17α-methyl-5α-androst-2-eno[3,2c]pyrazol) is a testosterone analogue with the same anabolic effect like testosterone but its ring structure makes it possible to take it orally. Therefore, stanozolol is one of the most frequently used anabolic steroids. Common verification methods for anabolic drugs exist, identifying the chemicals in tissues, like hair or blood samples. The idea of this feasibility study was to search for specific gene expression regulations induced by stanozolol to identify the possible influence of the synthetically hormone on different metabolic pathways. Finding biomarkers for anabolic drugs could be supportive of the existing methods and an additional proof for illegal drug abuse. In two separate cell cultures, human HFDPC (hair follicle dermal papilla cells) from a female and a male donor were treated with stanozolol. In the female cell culture treatment concentrations of 0 nM (control), 1 nM, 10 nM and 100 nM were chosen. Cells were taken 0 h, 6 h, 24 h and 48 h after stimulation and totalRNA was extracted. Learning from the results of the pilot experiment, the male cell culture was treated in 10 nM and 100 nM concentrations and taken after 0 h, 6 h, 24 h and 72 h. Using quantitative real-time RT-PCR expression of characteristics of different target genes were analysed. Totally 13 genes were selected according to their functionality by screening the actual literature and composed to functional groups: factors of apoptosis regulation were Fas Ligand (FasL), its receptor (FasR), Caspase 8 and Bcl-2. Androgen receptor (AR) and both estrogen receptors (ERα, ERβ) were summarized in the steroid receptor group. The growth factor group included the insulin like growth factor receptor (IGF1R) and growth hormone receptor (GHR). Fibroblast growth factor 2 (FGF2) and keratinocyte growth factor (FGF7) were summarized in the hair cycle factor group. 5α-Steroidreductases (SRD5A1, SRD5A2) represented the enzyme group. Three reference genes were taken for relative quantification: ubiquitin (UBQ), glycerinaldehyde-3-phsophate-dehydrogenase (GAPDH), and β-actin (ACTB). In cell culture 1 AR, FasR, FGF2 showed significant regulations within one treatment time, significant gene expressions over time were analysed for Caspase 8. In cell culture 2 AR, FasR and SRD5A2 were significantly regulated within one treatment time. In this feasibility study first biomarker for a screening pattern of anabolic agents could be identified providing the rationality to investigate modified, metabolic pathways in the whole hair follicle.

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Asokakumar, Anjana, Juan P. Hernandez, Rui Xiao, David D. Moore e Sayeepriyadarshini Anakk. "PMON251 Loss of Constitutive Androstane Receptor, CAR reduces the serum androgens levels and alters reproductive function". Journal of the Endocrine Society 6, Supplement_1 (1 novembre 2022): A698. http://dx.doi.org/10.1210/jendso/bvac150.1440.

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Abstract The nuclear receptor, Constitutive Androstane Receptor (CAR/NR1i3) is extensively known for its detoxification function in the liver. We have identified the role of CAR in regulating androgen levels and regulating testis function. Although the inactivation of CAR by the sex hormone axis via androstanol has been known for decades, its role in regulating reproduction has not been addressed. On examining the WT mice and the global CARKO mice, we found that CARKO mice have reduced serum testosterone and androstanol levels. Further, the levels of the steroidogenic gene, Srd5a1 was significantly reduced. This result correlated well with reduced anogenital distance in males, increased anxiety and subfertility. However, we did not find differences in the expression of detoxification genes in the CARKO testis. Histological analysis of the testis of the CARKO mice revealed abnormal Leydig cells and Oil Red O staining showed lipid accumulation in the Leydig cell island. We are currently examining the effect of the reduced androgens in the hypothalamic-pituitary-gonadal axis in the CARKO mice model. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

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Fakhry Gazal Mohammad e Adnan F. AL-Azzawie. "Assessment of Steroid 5 Alpha Reductase Enzyme Levels and Its Correlation with Sex Hormones in Infertile Iraqi Men". International Journal for Research in Applied Sciences and Biotechnology 7, n. 6 (19 dicembre 2020): 227–33. http://dx.doi.org/10.31033/ijrasb.7.6.32.

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This study aims to evaluate the 5-alpha reductase enzyme (SRD5A2) levels in serum and it’s association with some sex hormones such as Follicle stimulating hormone (FSH), Luteinizing hormone (LH), prolactin and testosterone hormone and the infertility type in some infertile Iraqi men. Blood and seminal fluid samples from (60) idiopathic male infertile and (30) healthful individuals as a control group aged (18 to 60 year) are collected from private clinics. Enzyme Linked Immunosorbent Assay (ELISA) has been used for estimation of serum SRD5A as enzymes and FSH, LH, prolactin and testosterone as hormones.According to types of sperm count patients have been divided to two group 49 person as azoospermia group (zero /ml) and 11 person as oligospermia group less than 20 million/ml. The levels of SRD5A2 and testosterone are significantly decreased to (P≤0.01) in the infertile men as compared with control group. While the level of FSH, LH and prolactin are significantly higher (P≤ 0.01) in the infertile men than control group. The results of SRD5A2 are non-significant, while, levels of FSH, LH and prolactin are higher significant (P≤ 0.01) except testosterone level which has significant differences (P≤ 0.05) in the age groups <20-30 year, 31–40 year and ≥ 40 year. There are significant differences (P≤ 0.01) in levels of SRD5A2, FSH and prolactin, but the levels of LH are non-significant in the infertility period ≤ 10 year, 11 – 20 year, ≥ 20 year. Smoker infertile men have low levels (P≤ 0.01) in the SRD5A2 and prolactin while have high levels in the LH hormones compared with control. Patients with family history have shown significant differences (P≤0.05) in the levels of SRD5A2, testosterone, LH and prolactin. In conclusion, this study revealed significantly decrease in the levels ofSRD5A2 in the Azoospermic and oligospermic infertile men and significant negative correlation (P<0.05) between SRD5A2 pg/ml and FSH (mIu/ml) R factor-0.328. Therefore, SRD5A2 has important role in the diagnosis of idiopathic male infertility and it's one of the important markers in the diagnosis of normal spermatogenesis.

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