Determination of rat 5α-reductase type 1 isozyme activity and its inhibition by novel steroidal oxazolines

Androgens, particularly testosterone and dihydrotestosterone (DHT), played crucial roles in prostate development and pathology, with DHT being converted from testosterone by 5α‐reductase isozymes. Two isozymes were identified, with 5α‐reductase‐2 being predominant in the human prostate. Mutations in the 5α‐reductase‐2 gene caused a deficiency syndrome, leading to a small, rudimentary prostate in affected individuals, who did not develop benign prostate hyperplasia (BPH) or prostate cancer. Animal studies with 5α‐reductase‐2 gene knockout or specific inhibitors also showed reduced prostate size. These isozymes were key targets for preventing and treating BPH and prostate cancer, and androgen actions on prostate gene expression and growth were modulated by estrogen receptor ligands. The research underscored the significance of 5α‐reductase isozymes in male sexual differentiation and prostate health.

The enzyme 5 alpha-reductase (5 alpha R) catalyzed the conversion of testosterone into dihydrotestosterone (DHT), which was linked to conditions like benign prostatic hyperplasia, prostate cancer, acne, androgenetic alopecia in men, and hirsutism in women. Two isozymes, 5 alpha R-1 and 5 alpha R-2, were identified, each with distinct characteristics and tissue distributions, suggesting different roles in disease pathogenesis. The development of selective inhibitors for these isozymes, particularly non-steroidal inhibitors targeting 5 alpha R-1, was a significant focus in pharmaceutical research to create more specific treatments for DHT-related disorders. The paper reviewed major classes of these inhibitors and discussed biological tests for their efficacy.