Functional interaction between gonadotropin-releasing hormone and PACAP in gonadotropes and alpha T3-1 cells.

Gonadotropes, like other cells, receive informational input from multiple receptor types, acting through multiple intracellular signaling pathways, and are therefore faced with the task of integrating this input in order to respond appropriately to their environment. In recent years an increasing number of examples of functional interactions occurring between the PIC and adenylyl cyclase signaling pathways in gonadotropes have been described, and the discovery that these cells are targets for PACAP has provided a physiological context for earlier work on gonadotrope regulation by cyclic AMP. The development of the alpha T3-1 cell line has greatly facilitated investigation of the interaction between these signaling systems. In these cells we have obtained no evidence for interaction between the GnRH and PACAP receptor-effector systems at the level of receptor occupancy or expression, but these systems clearly do have reciprocal modulatory effects on second messenger generation and/or mobilization. We are now faced with the challenge of determining the physiological and/or pathophysiological relevance of such interactions.