SRD5A1

3-oxo-5-alpha-steroid 4-dehydrogenase 1 is an is_associated_with::enzyme that in humans is encoded by the SRD5A1 is_associated_with::gene.

Steroid 5-alpha-reductase (EC 1.3.99.5) catalyzes the conversion of is_associated_with::testosterone into the more potent is_associated_with::androgen, is_associated_with::dihydrotestosterone (DHT). There are 2 isoforms of the is_associated_with::enzyme: SRD5A1 and is_associated_with::SRD5A2.

Regulation
is_associated_with::ETV4 family members bind to ETS DNA-binding sites and both regulate their own expression and the transcription of a subset of genes that are dependent upon testicular luminal fluid factors, including Ggt_pr4, SRD5A1, and Gpx5.

6-month dietary is_associated_with::vitamin E (VE) deficiency in rats resulted in a twofold increase in the mRNA level of SRD5A1 gene and a twofold decrease in the mRNA level of GCLM gene but is not directly mediated by changes in promoter DNA methylation.

Insulin increases the expression of 5α-reductase type 1 mRNA via Akt signalling suggest that elevated levels of 5α-reduced androgens seen in hyperinsulinemic conditions might be explained on the basis of a stimulatory effect of insulin on 5α-reductase in granulosa cells leading to impaired follicle growth and ovulation.

Clinical significance
is_associated_with::Hyperinsulinemia acutely enhances is_associated_with::ACTH effects on both the androgen and glucocorticoid pathways leading to changes in steroid metabolites molar ratios that suggest insulin stimulation of 5 α-reductase activity.

is_associated_with::PCOS is associated with enhanced androgen and cortisol metabolite excretion and increased 5 alpha-reductase activity that cannot be explained by obesity alone. Increased adrenal corticosteroid production represents an important pathogenic pathway in PCOS.

Progression to is_associated_with::castration-resistant prostate cancer (CRPC) is accompanied by increased expression of SRD5A1 over is_associated_with::SRD5A2, which is otherwise the dominant isoenzyme expressed in the prostate. The dominant route of DHT synthesis in human CRPC bypasses testosterone, and instead requires 5α-reduction of is_associated_with::androstenedione by SRD5A1 to is_associated_with::5α-androstanedione, which is then converted to DHT fuelling cancer growth.