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Science 29 June 1990:
Vol. 248. no. 4963, pp. 1663 - 1666
DOI: 10.1126/science.2163546
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Articles

Science, Vol 248, Issue 4963, 1663-1666
Copyright © 1990 by American Association for the Advancement of Science

articles

Endothelin stimulation of cytosolic calcium and gonadotropin secretion in anterior pituitary cells

SS Stojilkovic, F Merelli, T Iida, LZ Krsmanovic, and KJ Catt

Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.

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 a 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 diacyglycerol. Although intracellular calcium concentration and gonadotropin secretory responses to endothelin were independent to 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.


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