Possible neuroendocrine actions of endothelin-3.
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.
Samson
W K
WK
Department of Anatomy and Neurobiology, University of Missouri School of Medicine, Columbia 65212.
Skala
K D
KD
Alexander
B
B
Huang
F L
FL
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D016232:Endothelins / Q000502:physiology*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism; D008297:Male; D009490:Neurosecretory Systems / Q000166:cytology / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000378:metabolism; D011388:Prolactin / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains
D016232:Endothelins; D007987:Gonadotropin-Releasing Hormone; D011388:Prolactin; D007986:Luteinizing Hormone; D013006:Growth Hormone; D009543:Nifedipine