dihydrotestosterone

DHT is synthesized from testosterone by the enzyme 5α-reductase (type 1 in skin/liver, type 2 in prostate, genital skin, and hair follicles). It binds androgen receptors with greater affinity and stability than testosterone, making it 2-3x more potent.

Embryology: DHT is critical for differentiation of male external genitalia (penis, scrotum, prostate) from the urogenital sinus/tubercle in the 8th-12th week of gestation. Testosterone alone drives internal genitalia (Wolffian duct derivatives - epididymis, vas deferens, seminal vesicles), while DHT is required for external masculinization.

Clinical correlations: - 5α-reductase deficiency: autosomal recessive condition causing ambiguous genitalia or female-appearing external genitalia at birth in genetically XY males, with normal internal male structures (since testosterone-dependent). At puberty, increased testosterone can cause virilization ("penis at 12" syndrome) due to residual enzyme activity or type 1 isoenzyme. - Androgen insensitivity syndrome (AIS): defective androgen receptor; unlike 5α-reductase deficiency, patients have female external genitalia and typically no virilization at puberty; testes present but undescended, blind vaginal pouch, no uterus (due to AMH from testes). - Benign prostatic hyperplasia (BPH): DHT promotes prostatic stromal and epithelial growth; treated with 5α-reductase inhibitors (finasteride, dutasteride). - Androgenetic alopecia (male pattern baldness): DHT-mediated hair follicle miniaturization; also treated with finasteride. - Acne: DHT stimulates sebaceous gland activity.

Pharmacology: Finasteride/dutasteride inhibit 5α-reductase, reducing DHT levels—used for BPH and hair loss; can cause decreased libido and erectile dysfunction as side effects.