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 Ca 2+ 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 InsP 3 production and InsP 3 dependent Ca 2+ 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 Ca 2+ 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 Ca 2+ concentration.