Endothelin-3 stimulates luteinizing hormone-releasing hormone (LHRH) secretion from LHRH neurons by a prostaglandin-dependent mechanism.
Endothelin (ET) peptides have recently been recognized as putative regulators of the endocrine system. Particularly in the gonadal system, ET-3 stimulates LH secretion from anterior pituitary cells cultured in vitro. In these studies, we evaluate the actions of ET-3, the most abundant species of the ET family in the central nervous system, on LHRH release from arcuate nucleus-median eminence (AN-ME) fragments and an LHRH-secreting neuronal cell line (GT1 cells) in vitro. ET-3 exhibited a stimulatory effect on LHRH secretion from AN-ME fragments and GT1 cells incubated in a static system as well as in a dynamic perifusion paradigm. In all the systems used, the effects of ET-3 on LHRH secretion showed a dose dependency. The increase in LHRH secretion induced by ET-3 was accompanied by an increased secretion of prostaglandin E2 (PGE2), not only in the AN-ME incubations, but also in the GT1 incubation and perifusion systems. Blockade of arachidonic acid and/or PG synthesis significantly reduced the ET-3-induced LHRH and concomitant PGE2 release from both AN-ME fragments and GT1 cells incubated in vitro. In AN-ME incubations, ET-3 effects were enhanced by potassium-induced depolarization. This suggests that activation of other transmitter system(s) may be needed for obtaining a physiological activation of the LHRH neuronal system. In summary, in these studies we provide evidence for a direct action of ET-3 on the LHRH neuronal system. This action is exerted directly on LHRH neurons either at the level of the nerve terminals, the perikaryon, or both. In addition, the effects of ET-3 on LHRH release require a functional arachidonic acid metabolic pathway, particularly involving PG synthesis, in order to obtain stimulation, indicating that PGs are involved in the intracellular events leading to ET-3-evoked LHRH secretion.
Moretto
M
M
Reproductive Neuroendocrinology Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
López
F J
FJ
Negro-Vilar
A
A
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D002460:Cell Line; D003429:Cross Reactions; D015232:Dinoprostone / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011188:Potassium / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley
D016232:Endothelins; D015117:5,8,11,14-Eicosatetraynoic Acid; D007987:Gonadotropin-Releasing Hormone; D015232:Dinoprostone; D011188:Potassium; D007213:Indomethacin