Functional heterogeneity of pituitary gonadotropes in response to a variety of neuromodulators

Agents previously implicated in control of the hypothalamo-pituitary-gonadal axis were screened for their ability to regulate male rat gonadotropes directly. GnRH-evoked gonadotropin release is accompanied by oscillations of intracellular Ca2+ concentration ([Ca2+]i) and of an outward K+ current that is activated by Ca2+. Substances that caused current responses similar to those with GnRH were hypothesized to evoke secretion. Endothelin-1, oxytocin, neurotensin, pituitary adenylate cyclase-activating polypeptide, and serotonin raised [Ca2+]i and evoked LH release as assayed by the reverse hemolytic plaque assay. These agents affected only subpopulations of gonadotropes establishing functional heterogeneity of pituitary gonadotropes. One neuromodulator (ATP) evoked ionic current in all gonadotropes but the current was different than that evoked by GnRH. Many other substances, including galanin and neuropeptide Y, caused no changes in currents and were considered not to affect [Ca2+]i and not to be secretagogues for gonadotropes.