Dual action of androgen on calcium signaling and luteinizing hormone secretion in pituitary gonadotrophs.
An increase in serum androgen levels associated with a suppression of cyclic gonadotropin secretion is frequently observed in females with impaired ovarian function. Here, we addressed the hypotheses that androgens (testosterone and dihydrotestosterone) alter gonadotropin secretion by modulating agonist-induced Ca2+ signaling and/or Ca(2+)-controlled exocytosis. In mixed populations of pituitary cells from female rats, addition of testosterone reduced basal and agonist (GnRH)-induced gonadotropin secretion in a concentration- and time-dependent manner. The suppressive actions of this androgen on gonadotropin secretion were observed over the full GnRH concentration range. Reduction in agonist-induced gonadotropin secretion was also observed after addition of dihydrotestosterone, indicating that the inhibitory action of testosterone is not mediated by its conversion to estradiol. Both the extracellular Ca(2+)-independent spike phase and extracellular Ca(2+)-dependent sustained phase of GnRH-induced gonadotropin secretions were affected by testosterone. In part, the inhibitory action of testosterone was mediated by attenuation of GnRH-induced InsP3 production and InsP3-dependent Ca2+ mobilization. In addition, testosterone exhibited a Ca(2+)-independent action on gonadotropin secretion, as documented by attenuation of high potassium-induced secretion without an affect on depolarization-induced Ca2+ signals. These results suggest that androgen inhibition of gonadotropin secretion occurs at two distinct steps in the secretory pathway, one prior to and one after elevation in cytosolic Ca2+ concentration.
Ortmann
O
O
Department of Obstetrics and Gynecology, Medical University Luebeck, Germany.
Tomic
M
M
Weiss
J M
JM
Diedrich
K
K
Stojilkovic
S S
SS
D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects*; D013196:Dihydrotestosterone / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000378:metabolism; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D006062:Gonadotropins / Q000378:metabolism; D007986:Luteinizing Hormone / Q000187:drug effects / Q000378:metabolism*; D010902:Pituitary Gland / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000378:metabolism / Q000494:pharmacology; D013997:Time Factors
D000728:Androgens; D006062:Gonadotropins; D013196:Dihydrotestosterone; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D004958:Estradiol; D007986:Luteinizing Hormone