Evidence for a negative ultrashort loop feedback mechanism operating on the luteinizing hormone-releasing hormone neuronal system.
The present studies were designed to determine whether an ultrashort loop feedback mechanism is involved in the regulation of LHRH secretion. Daily administration of a highly potent LHRH agonist (LHRH-AGO; [D-Ala6,Des-Gly10] LHRH ethylamide) immediately after orchidectomy (ORDX) significantly attenuated the rise of plasma LH from days 2 through 10 after ORDX. Concomitantly with the diminished LH rise after ORDX, a significant increase in LHRH content in the arcuate nucleus was observed in LHRH-AGO-treated rats. Measurement of LHRH levels in hypophyseal portal blood in rats 10 days after ORDX combined with daily agonist treatment revealed a significant decrease in LHRH values in portal plasma compared with those in orchidectomized controls. Arcuate nuclei-median eminence (ME) fragments obtained from ORDX rats treated in vivo with LHRH-AGO for 5 days showed a decreased basal secretion of LHRH and a diminished response to K+ stimulation compared with the release from fragments obtained from ORDX saline-treated controls. To evaluate whether a tonic LHRH inhibitory activity operates within the ME, additional experiments were performed in which ME fragments were incubated in vitro in the presence of a potent LHRH antagonist [( D-pGlu1,D-Phe2,D-Trp3,6]LHRH). The antagonist significantly enhanced the basal secretion of LHRH in a dose-dependent manner. The latter results suggest that LHRH antagonists may enhance LHRH release, perhaps by interacting with LHRH receptors playing an inhibitory role on the endogenous secretion of the decapeptide. These observations strongly suggest a tonic inhibitory or modulatory role of LHRH neurons in the regulation of their own function.
Valença
M M
MM
Reproductive Neuroendocrinology Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Johnston
C A
CA
Ching
M
M
Negro-Vilar
A
A
D000818:Animals; D005246:Feedback; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008473:Median Eminence / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D009919:Orchiectomy; D051381:Rats; D011919:Rats, Inbred Strains
D007987:Gonadotropin-Releasing Hormone; C010661:surfagon