Altered expression of SRD5A2 gene

IN BRIEF: The gene SRD5A2 expresses enzyme 5-alpha reductase type 2. This enzyme is inhibited by finasteride and dutasteride (but see differences in pharmacology). Organs and tissues with higher SRD5A2 expression are expected to have a greater response to the drug’s inhibitory action. SRD5A2 expression is elevated in the male reproductive system, liver and lung (see chart) as well as the brain. Castelli et al. (2013) found evidence of the enzyme in most brain regions, including “critical regions for behavioral regulation.” A mutation of SRD5A2 causes 5-alpha reductase deficiency, a disorder of sexual development.

Expression of SRD5A2 gene by tissue type. There was significant expression of SRD5A2 in liver, prostate, bladder, testis and lung. Source: NCBI Gene

See also: Related research: Genetics

2020s

Jin R, Forbes C, Miller NL, et al. Glucocorticoids are induced while dihydrotestosterone levels are suppressed in 5-alpha reductase inhibitor treated human benign prostate hyperplasia patients. Prostate. 2022. doi:10.1002/pros.24410PubMed

Lin ZM, Fan DD, Jin S, Liu ZL, Niu YN. Methylated CpG dinucleotides in the 5-α reductase 2 gene may explain finasteride resistance in benign prostatic enlargement patients. Asian J Androl. 2021. doi:10.4103/aja.aja_63_20PubMed • PMC full text

Wang Z, Deng T, Long X, et al. Methylation of SRD5A2 promoter predicts a better outcome for castration-resistant prostate cancer patients undergoing androgen deprivation therapy. PLoS One. 2020. doi:10.1371/journal.pone.0229754PubMed• PMC full text

Xiao Q, Wang L, Supekar S, et al. Structure of human steroid 5α-reductase 2 with anti-androgen drug finasteride. Res Sq [Preprint]. 2020. doi:10.21203/rs.3.rs-40159/v1PubMed • PMC full text

Xue B, Wu S, Sharkey C, et al. Obesity-associated inflammation induces androgenic to estrogenic switch in the prostate gland. Prostate Cancer Prostatic Dis. 2020 Sep. doi:10.1038/s41391-020-0208-4 • PubMed • PMC full text

2010s

Basaria S, Jasuja R, Huang G, et al. Characteristics of men who report persistent sexual symptoms after finasteride use for hair loss. J Clin Endocrinol Metab. 2016. doi:10.1210/jc.2016-2726PubMed • PMC full text

Bissegger S, Langlois VS. Androgens modulate gene expression and specific DNA methylation pattern of steroid 5α-reductases in the frog Silurana tropicalis. Gen Comp Endocrinol. 2016. doi:10.1016/j.ygcen.2016.03.021PubMed [Study does not involve finasteride]

Ge R, Wang Z, Bechis SK, et al. DNA methyl transferase 1 reduces expression of SRD5A2 in the aging adult prostate. Am J Pathol. 2015. doi:10.1016/j.ajpath.2014.11.020PubMed • PMC full text

[Commentary] Isaacs JT. Lessons learned about prostatic transformation from the age-related methylation of 5α-reductase type 2 gene. Am J Pathol. 2015 Mar. doi:10.1016/j.ajpath.2015.01.001PubMedPMC full text

Melcangi RC, Casarini L, Marino M, et al. Altered methylation pattern of the SRD5A2 gene in the cerebrospinal fluid of post-finasteride patients: a pilot study. Endocrine Connections. 2019. doi:10.1530/EC-19-0199PubMed • PMC full text

Rongbin G, Wang Z, Bechis S, et al. Abstract 1052: Variable expression of 5-alpha reductase 2 in the aging adult prostate is regulated by DNA methylation. Cancer Research. 2015;75(15_Supplement):1052. doi:10.1158/1538-7445.AM2015-1052

Wang Z, Hu L, Salari K, et al. Androgenic to oestrogenic switch in the human adult prostate gland is regulated by epigenetic silencing of steroid 5α-reductase 2. J Pathol. 2017. doi:10.1002/path.4985PubMed • PMC full text

Windahl SH, Andersson N, Börjesson AE, et al. Reduced bone mass and muscle strength in male 5α-reductase type 1 inactivated mice. PLoS One. 2011. doi:10.1371/journal.pone.0021402PubMedPMC full text

2000s

Oakes CC, La Salle S, Smiraglia DJ, Robaire B, Trasler JM. A unique configuration of genome-wide DNA methylation patterns in the testis. Proc Natl Acad Sci U S A. 2007. doi:10.1073/pnas.0607521104PubMed • PMC full text

1990s

Berman DM, Tian H, Russell DW. Expression and regulation of steroid 5 alpha-reductase in the urogenital tract of the fetal rat. Mol Endocrinol. 1995. doi:10.1210/mend.9.11.8584033PubMed

“In the adult prostate, 5 alpha-reductase gene expression is under feedforward control, in which the product of the enzyme, dihydrotestosterone, stimulates the expression of the gene.”

Reyes EM, Camacho-Arroyo I, Nava G, Cerbón MA. Differential methylation in steroid 5 alpha-reductase isozyme genes in epididymis, testis, and liver of the adult rat. J Androl. 1997. doi:10.1002/j.1939-4640.1997.tb01941.x • PubMed • Via journal site

Viger RS, Robaire B. The mRNAs for the steroid 5 alpha-reductase isozymes, types 1 and 2, are differentially regulated in the rat epididymis. J Androl. 1996. doi:10.1002/j.1939-4640.1996.tb00583.x • PubMedVia journal site