In 1974, a lack of 5α-dihydrotestosterone (5α-DHT), the most potent androgen 
across species except for fish, was shown to be the origin of a type of 
pseudohermaphrodism in which boys have female-like external genitalia. This 
human intersex condition is linked to a mutation in the steroid-5α-reductase 
type 2 (SRD5α2) gene, which usually produces an important enzyme capable of 
reducing the Δ4-ene of steroid C-19 and C-21 into a 5α-stereoisomer. Seeing the 
potential of SRD5α2 as a target for androgen synthesis, pharmaceutical companies 
developed 5α-reductase inhibitors (5ARIs), such as finasteride (FIN) and 
dutasteride (DUT) to target SRD5α2 in benign prostatic hyperplasia and 
androgenic alopecia. In addition to human treatment, the development of 5ARIs 
also enabled further research of SRD5α functions. Therefore, this review details 
the morphological, physiological, and molecular effects of the lack of SRD5α 
activity induced by both SRD5α mutations and inhibitor exposures across species. 
More specifically, data highlights 1) the role of 5α-DHT in the development of 
male secondary sexual organs in vertebrates and sex determination in 
non-mammalian vertebrates, 2) the role of SRD5α1 in the synthesis of the 
neurosteroid allopregnanolone (ALLO) and 5α-androstane-3α,17β-diol (3α-diol), 
which are involved in anxiety and sexual behavior, respectively, and 3) the role 
of SRD5α3 in N-glycosylation. This review also features the lesser known 
functions of SRD5αs in steroid degradation in the uterus during pregnancy and 
glucocorticoid clearance in the liver. Additionally, the review describes the 
regulation of SRD5αs by the receptors of androgens, progesterone, estrogen, and 
thyroid hormones, as well as their differential DNA methylation. Factors known 
to be involved in their differential methylation are age, inflammation, and 
mental stimulation. Overall, this review helps shed light on the various 
essential functions of SRD5αs across species.