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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.[4]
6-month dietary 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.[5]
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.[6]
Clinical significance
Hyperinsulinemia acutely enhances 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. [7]
PCOS is associated with enhanced androgen and cortisol metabolite excretion and increased 5α-reductase activity that cannot be explained by obesity alone. Increased adrenal corticosteroid production represents an important pathogenic pathway in PCOS.[8]
Progression to castration-resistant prostate cancer (CRPC) is accompanied by increased expression of SRD5A1 over 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 androstenedione by SRD5A1 to 5α-androstanedione, which is then converted to DHT fuelling cancer growth.[9]
↑Jenkins EP, Hsieh CL, Milatovich A, Normington K, Berman DM, Francke U, Russell DW (Dec 1991). "Characterization and chromosomal mapping of a human steroid 5 alpha-reductase gene and pseudogene and mapping of the mouse homologue". Genomics. 11 (4): 1102–12. doi:10.1016/0888-7543(91)90038-G. PMID1686016.
↑Yang L, Fox SA, Kirby JL, Troan BV, Hinton BT (Apr 2006). "Putative regulation of expression of members of the Ets variant 4 transcription factor family and their downstream targets in the rat epididymis". Biology of Reproduction. 74 (4): 714–20. doi:10.1095/biolreprod.105.044354. PMID16394217.
↑Fischer A, Gaedicke S, Frank J, Döring F, Rimbach G (Oct 2010). "Dietary vitamin E deficiency does not affect global and specific DNA methylation patterns in rat liver". The British Journal of Nutrition. 104 (7): 935–40. doi:10.1017/S0007114510001649. PMID20447326.
↑Tosi F, Negri C, Brun E, Castello R, Faccini G, Bonora E, Muggeo M, Toscano V, Moghetti P (Feb 2011). "Insulin enhances ACTH-stimulated androgen and glucocorticoid metabolism in hyperandrogenic women". European Journal of Endocrinology / European Federation of Endocrine Societies. 164 (2): 197–203. doi:10.1530/EJE-10-0782. PMID21059865.
↑Vassiliadi DA, Barber TM, Hughes BA, McCarthy MI, Wass JA, Franks S, Nightingale P, Tomlinson JW, Arlt W, Stewart PM (Sep 2009). "Increased 5 alpha-reductase activity and adrenocortical drive in women with polycystic ovary syndrome". The Journal of Clinical Endocrinology and Metabolism. 94 (9): 3558–66. doi:10.1210/jc.2009-0837. PMID19567518.
Moore RJ, Wilson JD (Feb 1972). "Localization of the reduced nicotinamide adenine dinucleotide phosphate: 4 -3-ketosteroid 5 -oxidoreductase in the nuclear membrane of the rat ventral prostate". The Journal of Biological Chemistry. 247 (3): 958–67. PMID4400474.
Milewich L, Kaimal V, Toews GB (May 1983). "Androstenedione metabolism in human alveolar macrophages". The Journal of Clinical Endocrinology and Metabolism. 56 (5): 920–4. doi:10.1210/jcem-56-5-920. PMID6833469.
Antonipillai I, Wahe M, Yamamoto J, Horton R (Jan 1995). "Activin and inhibin have opposite effects on steroid 5 alpha-reductase activity in genital skin fibroblasts". Molecular and Cellular Endocrinology. 107 (1): 99–104. doi:10.1016/0303-7207(94)03430-2. PMID7796940.
Ellis JA, Stebbing M, Harrap SB (Jun 1998). "Genetic analysis of male pattern baldness and the 5alpha-reductase genes". The Journal of Investigative Dermatology. 110 (6): 849–53. doi:10.1046/j.1523-1747.1998.00224.x. PMID9620288.
Zhou Z, Shackleton CH, Pahwa S, White PC, Speiser PW (Mar 1998). "Prominent sex steroid metabolism in human lymphocytes". Molecular and Cellular Endocrinology. 138 (1–2): 61–9. doi:10.1016/S0303-7207(98)00052-5. PMID9685215.
Eminović I, Liović M, Prezelj J, Kocijancic A, Rozman D, Komel R (2002). "New steroid 5alpha-reductase type I (SRD5A1) homologous sequences on human chromosomes 6 and 8". Pflügers Archiv. 442 (6 Suppl 1): R187–9. doi:10.1007/s004240100019. PMID11678334.
Ellis JA, Wong ZY, Stebbing M, Harrap SB (Dec 2001). "Sex, genes and blood pressure". Clinical and Experimental Pharmacology & Physiology. 28 (12): 1053–5. doi:10.1046/j.1440-1681.2001.03579.x. PMID11903314.
Rodríguez-Dorantes M, Lizano-Soberón M, Camacho-Arroyo I, Calzada-León R, Morimoto S, Téllez-Ascencio N, Cerbón MA (Mar 2002). "Evidence that steroid 5alpha-reductase isozyme genes are differentially methylated in human lymphocytes". The Journal of Steroid Biochemistry and Molecular Biology. 80 (3): 323–30. doi:10.1016/S0960-0760(02)00023-7. PMID11948017.
Ha SJ, Kim JS, Myung JW, Lee HJ, Kim JW (Apr 2003). "Analysis of genetic polymorphisms of steroid 5alpha-reductase type 1 and 2 genes in Korean men with androgenetic alopecia". Journal of Dermatological Science. 31 (2): 135–41. doi:10.1016/S0923-1811(02)00145-7. PMID12670724.
Habib FK, Ross M, Bayne CW, Bollina P, Grigor K, Chapman K (May 2003). "The loss of 5alpha-reductase type I and type II mRNA expression in metastatic prostate cancer to bone and lymph node metastasis". Clinical Cancer Research. 9 (5): 1815–9. PMID12738739.