Danazol suppression of luteinizing hormone secretion: a role for danazol-androgen receptor interaction within the brain-pituitary complex.
We investigated the relationship between intracellular androgen and estrogen receptors within the brain-pituitary complex and danazol suppression of luteinizing hormone secretion in castrated rats. Danazol did not influence 3H-estradiol-estrogen receptor interactions within the brain and pituitary but did suppress 3H-dihydrotestosterone-androgen receptor interactions within this neuroendocrine complex. To study the significance of these danazol-androgen receptor interactions, the drug was administered to androgen receptor-deficient pseudohermaphrodite or flutamide-treated male rats. In both instances, danazol suppression of luteinizing hormone release was markedly attenuated or absent. These findings point to danazol-androgen receptor interactions within the brain-pituitary complex as a key step in this drug's antigonadotropic actions. Whether the active drug form is danazol itself or a metabolite is subject to further study.
D000679:Amygdala / Q000502:physiology; D000818:Animals; D001921:Brain / Q000502:physiology*; D003613:Danazol / Q000494:pharmacology*; D013196:Dihydrotestosterone / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism; D005260:Female; D005485:Flutamide / Q000494:pharmacology; D007031:Hypothalamus / Q000502:physiology; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism*; D008297:Male; D010902:Pituitary Gland / Q000502:physiology*; D011245:Pregnadienes / Q000494:pharmacology*; D011301:Preoptic Area / Q000502:physiology; D051381:Rats; D011944:Receptors, Androgen / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D011987:Receptors, Steroid / Q000502:physiology*; D013997:Time Factors
D011245:Pregnadienes; D011944:Receptors, Androgen; D011987:Receptors, Steroid; D013196:Dihydrotestosterone; D004958:Estradiol; D005485:Flutamide; D007986:Luteinizing Hormone; D003613:Danazol