Norepinephrine amplifies human chorionic gonadotropin-stimulated androgen biosynthesis by ovarian theca-interstitial cells.
Ovarian theca-interstitial cells, when cultured in serum-free medium, secreted androgens in response to hCG stimulation. This production was dependent on time (maximum production attained after 96 h) and dose (half-maximal effective dose of hCG, 9 ng/ml). When the sympathomimetics norepinephrine, epinephrine, and isoproterenol were added to the medium, androgen production in response to hCG was enhanced by 100-300%. The ability of the catecholamines to stimulate androgen production was dependent on the continuous presence of hCG. Treatment with catecholamines alone did not induce theca-interstitial cells to produce androgens. Catecholamine stimulation of steroid hormone metabolism was selective for intermediates in the delta 4-pathway, with greatest increases occurring in the production of androstenedione and testosterone. It was found that the effect of the catecholamines on androgen production was dependent on both beta 1-and beta 2-adrenergic receptors. The acquisition of catecholamine responsiveness was specific to hCG; if theca-interstitial cells were induced to differentiate with either prostaglandin E2 or cholera toxin, then isoproterenol did not enhance androgen synthesis. The catecholamine-induced increases in androgen production were not due to a granulosa cell contribution of steroid. The interstitial cells are the only steroid-producing cells in the ovary that are directly innervated by norepinephrine-containing fibers of the sympathetic nervous system. Our finding of catecholamine-augmented androgen production provides a direct link between the autonomic nervous system and regulation of ovarian steroid synthesis.
D000728:Androgens / Q000096:biosynthesis*; D000735:Androstenedione / Q000096:biosynthesis; D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D006107:Granulosa Cells / Q000502:physiology; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D010053:Ovary / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical; D013799:Theca Cells / Q000378:metabolism*
D000728:Androgens; D006063:Chorionic Gonadotropin; D012739:Gonadal Steroid Hormones; D000735:Androstenedione; D007545:Isoproterenol; D009638:Norepinephrine; D004837:Epinephrine