Interaction of adenosine 3',5'-monophosphate derivatives with the gonadotropin-releasing hormone receptor on pituitary and ovary.

Abstract

Under some circumstances, exogenous cyclic nucleotides are reported to induce gonadotropin release from the anterior pituitary, although the role of endogenous cAMP in the acute actions of GnRH remains controversial. In this study, millimolar concentrations of 8-bromo cAMP, 8-hydroxy cAMP, (Bu)2cAMP, and cAMP itself,produced significant LH and FSH release from cultured male rat anterior pituitary cells. However, cells whose GnRH receptors were blocked with a 10-nM concentration of the potent GnRH antagonist [AcΔ3Pro1pFD-Phe2,DTrp3,6]GnRH failed to respond to the cAMP derivatives. Superfusion of the pituitary cells revealed that the cAMP analogs produced an increase in LH secretion within 3 min, and this effect was blocked by the antagonist in an equally rapid fashion. Although the GnRH antagonist completely blocked the stimulatory effects of GnRH and the cAMP analogs, it had no effect on LH secretion induced by the calcium ionophore A23187 or phorbol myristate acetate. To determine if the cyclic nucleotid...