biostudies-literatureLawrence BMMedical Research CouncilNational Health and Medical Research CouncilDHAC | National Health and Medical Research Council (NHMRC)e70177https://www.ebi.ac.uk/biostudies/studies/S-EPMC11698012biostudies-literatureUnknown38(22)Testosterone and dihydrotestosterone (DHT) are essential for male development and fertility. In the canonical androgen production pathway, testosterone is produced in the testis by HSD17B3; however, adult male Hsd17b3 knockout (KO) mice continue to produce androgens and are fertile, indicating compensatory mechanisms exist. A second, alternate pathway produces DHT from precursors other than testosterone via 5α-reductase (SRD5A) activity. We hypothesized that the alternate pathway contributes to androgen bioactivity in Hsd17b3 KO mice. To investigate contributions arising from and interactions between the canonical and alternate pathways, we pharmacologically inhibited SRD5A and ablated Srd5a1 (the predominant SRD5A in the testis) on the background of Hsd17b3 KO mice. Mice with perturbationFASEB journal : official publication of the Federation of American Societies for Experimental BiologyCompensatory mechanisms that maintain androgen production in mice lacking key androgen biosynthetic enzymes.PMC11698012APP1158344MR/N002970/1Smith SCurley MKO'Shaughnessy PJO'Donnell LLawrence BMDarbey ASmith LBGannon ALRebourcet DMackay RfalseCompensatory mechanisms that maintain androgen production in mice lacking key androgen biosynthetic enzymes.Testosterone and dihydrotestosterone (DHT) are essential for male development and fertility. In the canonical androgen production pathway, testosterone is produced in the testis by HSD17B3; however, adult male Hsd17b3 knockout (KO) mice continue to produce androgens and are fertile, indicating compensatory mechanisms exist. A second, alternate pathway produces DHT from precursors other than testosterone via 5α-reductase (SRD5A) activity. We hypothesized that the alternate pathway contributes to androgen bioactivity in Hsd17b3 KO mice. To investigate contributions arising from and interactions between the canonical and alternate pathways, we pharmacologically inhibited SRD5A and ablated Srd5a1 (the predominant SRD5A in the testis) on the background of Hsd17b3 KO mice. Mice with perturbation2024-01-01T00:00:00Z2024 Nov2025-04-22T09:02:57.409Z2025-04-05T22:50:40.45ZS-EPMC116980123955638710.1096/fj.202402093R