Endocrinology, Vol 128, 1465-1473, Copyright © 1991 by Endocrine Society

ARTICLES

Possible neuroendocrine actions of endothelin-3

WK Samson, KD Skala, B Alexander and FL Huang
Department of Anatomy and Neurobiology, University of Missouri School of Medicine, Columbia 65212.

The presence of endothelin (ET) immunoreactivity and binding sites in hypothalamus and pituitary gland suggests potential neuroendocrine actions of this family of vasoactive peptides. ET-3, the predominant member of the ET family in brain, exerted significant dose-related (1, 10, and 100 nM) inhibitory effects on PRL release from dispersed anterior pituitary cells in static incubations. The effect was not dependent on voltage-sensitive calcium channels, since the dihydropyridine calcium channel antagonist nifedipine failed to block this action. Nifedipine did, however, significantly reduce the transient acute stimulatory effect of ET-3 on PRL release in cultured cells incubated in dynamic perifusion. The longer lasting inhibitory effect on PRL release that followed the brief stimulatory action was not affected by nifedipine. ET-3 also stimulated a transient but significant release of LH from cells harvested from random cycle female rats, an effect that was not antagonized by a LHRH antagonist, but was blocked by nifedipine, suggesting the mobilization of extracellular calcium as a mechanism of action of ET-3. Nifedipine also reversed the acute stimulatory effect of ET-3 on GH secretion from these cells. Cerebroventricular injections of ET-3 (6 or 60 ng) failed to significantly alter PRL or LH secretion in conscious rats, suggesting that brain-derived ET does not act within the hypothalamus to alter the release of these two hormones. Similarly, iv infusion of even pressor doses of ET-3 (10, 30, or 300 ng) failed to significantly alter PRL, LH, or GH release; thus, it is unlikely that ET of peripheral origin acts within the gland. Our results suggest that locally produced ET may act as a neuroendocrine or paracrine factor controlling pituitary function in the rat.

This article has been cited by other articles:

				B. Kanyicska, A. Lerant, and M. E. Freeman Endothelin Is an Autocrine Regulator of Prolactin Secretion Endocrinology, December 1, 1998; 139(12): 5164 - 5173. [Abstract] [Full Text] [PDF]

				Y. Hiruma, A. Inoue, A. Shiohama, E. Otsuka, S. Hirose, A. Yamaguchi, and H. Hagiwara Endothelins inhibit the mineralization of osteoblastic MC3T3-E1 cells through the A-type endothelin receptor Am J Physiol Regulatory Integrative Comp Physiol, October 1, 1998; 275(4): R1099 - R1105. [Abstract] [Full Text] [PDF]

				N. A. Elshourbagy, J. E. Adamou, A. W. Gagnon, H.-L. Wu, M. Pullen, and P. Nambi Molecular Characterization of a Novel Human Endothelin Receptor Splice Variant J. Biol. Chem., October 11, 1996; 271(41): 25300 - 25307. [Abstract] [Full Text] [PDF]