The Response of Cultured Gonadotrophs to Inhibin: The Role of Calcium Mobilization

Abstract

The role of calcium mobilization and calmodulin activation in the induction of the selective suppression of follicle stimulating hormone (FSH) release by the gonadal protein inhibin was assessed employing a rat gonadotroph monolayer culture system. Inhibin, in porcine follicular fluid (60 ul/ml), did inhibit FSH release in the face of GnRH stimulation. Antagonism of calcium mobilization with verapamil (10^-4M) and dantrolene (10^-4M) failed to restore the FSH response when administered with GnRH and inhibin. Trifluoperazine (10^-4M), a calmodulin antagonist acted similarly. Cellular calmodulin content increased in response to gonadotropin-releasing hormone (GnRH), as did the concentration of cGMP, while both responses were prevented by the administration of inhibin. Trifluoperazine suppressed cGMP concentration to levels below baseline. These data suggest that while calmodulin and the cyclic nucleotides do not mediate the cellular response to inhibin, they may play a role in the control of gonadotropin synthesis. A link may exist between calmodulin, the concentration of which increased in response to GnRH and was suppressed by inhibin, and the elevation of cellular cGMP content induced by GnRH. Further investigation is warranted to assess a possible action of inhibin which is antagonistic to that of calcium in the transduction of GnRH stimulation into FSH release by the pituitary gonadotroph.