Dihydrotestosterone heptanoate: synthesis, pharmacokinetics, and effects on hypothalamic-pituitary-testicular function.
Dihydrotestosterone heptanoate (DHT-hp), a seven-carbon fatty acid ester of DHT, was synthesized, and its pharmacokinetics and effects on hypothalamic-pituitary-testicular function were determined in men and pubertal boys. Plasma DHT levels markedly increased 24 h after im injection of DHT-hp, reached their peak during the first week, and fell to baseline levels after 4-6 weeks. An estimated 43-55% of DHT-hp was converted to DHT 4-6 weeks after injection. Plasma testosterone, estradiol, LH, and FSH levels decreased by 4 days after DHT-hp injection, were lowest during the second week, and returned to baseline values after 4-6 weeks. The LH and FSH responses to GnRH were diminished by chronic administration of DHT-hp to pubertal boys at 3-week intervals for 15 weeks. The affinity of DHT-hp was 100 times less than the affinity of DHT for the human androgen receptor, and no affinity for the estrogen receptor in breast tissue could be demonstrated. Since DHT is a nonaromatizable androgen, and neither DHT nor DHT-hp binds readily to the estrogen receptor, suppression of LH and FSH secretion by this drug probably occurs via an androgen-dependent mechanism. Receptor binding and pharmacokinetic data indicate that unesterified DHT is the active principle. DHT-hp is a useful derivative of DHT, since prompt, predictable, and sustained rises in DHT occur after its administration.
D000328:Adult; D013196:Dihydrotestosterone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D004958:Estradiol / Q000378:metabolism; D006065:Gonadotropins, Pituitary / Q000378:metabolism; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010906:Pituitary Hormone-Releasing Hormones; D013737:Testis / Q000187:drug effects* / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism
D006065:Gonadotropins, Pituitary; D010906:Pituitary Hormone-Releasing Hormones; D013196:Dihydrotestosterone; C049564:dihydrotestosterone heptanoate; D013739:Testosterone; D004958:Estradiol