Gonadotropin-releasing hormone (GnRH) stimulates synthesis and release of the pituitary gonadotropins luteinizing hormone (LH) and follicle stimulating hormone (FSH). Other actions of GnRH include gonadotrope sensitization and desensitization as well as stimulation of GnRH receptor synthesis. Gonadotropin release initiated by increased intracellular calcium is a result of calcium mobilization from intracellular stores and influx of extracellular calcium through receptor-operated channels. Increases in intracellular calcium and the presence of both calmodulin and calmodulin binding-proteins in pituitary suggests that formation of Ca(2+)-calmodulin complexes and subsequent alteration of calmodulin-binding protein activity are likely important intermediate steps in the signaling pathway of LH release. Although activation of protein kinase C is not necessary for GnRH-stimulated LH release or gonadotrope desensitization, it appears to be essential for GnRH effects on LH beta gene expression. Therefore gonadotrope responses are apparently mediated by multiple intracellular signaling mechanisms.