GNRH AND PACAP ACTION IN GONADOTROPES - CROSS-TALK BETWEEN PHOSPHOINOSITIDASE-C AND ADENYLYL-CYCLASE MEDIATED SIGNALING PATHWAYS

In order to respond appropriately to their environment, gonadotropes, like other cells, must integrate informational input from multiple lig ands acting through multiple intracellular signaling pathways. In rece nt years, an increasing number of examples of functional interactions between the phosphoinositidase C (PIC) and adenylyl cyclase signaling pathways in gonadotropes have been described, and the discovery that t hese cells are targets for pituitary adenylyl cyclase activating pepti de (PACAP) has provided a physiological context for earlier work on go nadotrope regulation by cAMP. It has become clear that gonadotropes po ssess multiple PIC-coupled receptor types, in addition ta receptors ac tivating adenylyl and guanylyl cyclases, so that the potential for bot h coincidence signaling and cross-talk in these cells is immense; exam ples of both are seen in the effects of PACAP and GnRH on Ca2+ mobiliz ation and adenylyl cyclase activation in alpha T3-1 cells. In these ce lls, GnRH, acting via PiC-coupled receptors, can dramatically inhibit adenylyl cyclase activated by PACAP, bur can also alter cellular level s of protein kinase A subunits, providing a mechanism for coordinated regulation of both messenger and effector.