ENDOTHELIN STIMULATION OF CYTOSOLIC CALCIUM AND GONADOTROPIN-SECRETION IN ANTERIOR-PITUITARY-CELLS

The presence of endothelin, a vasoconstrictor peptide, in the hypothalamus and posterior pituitary suggests that it also regulates neural and other nonvascular target cells. In pituitary gonadotrophs, low doses of endothelin evoked oscillations in the intracellular calcium concentration, and high doses induced a biphasic calcium response. Mobilization of intracellular calcium predominated during the spike phase of the calcium response to endothelin, whereas calcium entry through dihydropyridine-sensitive channels contributed to both the spike and plateau phases of the calcium response. Endothelin was as potent as hypothalamic gonadotropin-releasing hormone (GnRH) in stimulation of gonadotropin release in perifused pituitary cells. Endothelin bound specifically to pituitary cells with a dissociation constant of 70 picomolar, and induced rapid formation of inositol trisphosphate and diacylglycerol. Although intracellular calcium concentration and gonadotropin secretory responses to endothelin were independent of the GnRH receptor, endothelin and GnRH appeared to have a common signal transduction mechanism. These observations suggest that endothelin can act as a neuropeptide to regulate anterior pituitary function.