Decrease in luteinizing hormone pulse frequency during a five-hour peripheral ghrelin infusion in the ovariectomized rhesus monkey.
Ghrelin, a nutrition-related peptide secreted by the stomach, is elevated during prolonged food deprivation. Because undernutrition is often associated with a suppressed reproductive axis, we have postulated that increasing peripheral ghrelin levels will decrease the activity of the GnRH pulse generator. Adult ovariectomized rhesus monkeys (n = 6) were subjected to a 5-h iv human ghrelin (100- to 150-microg bolus followed by 100-150 microg/h) or saline infusion, preceded by a 3-h saline infusion to establish baseline pulsatile LH release. Blood samples were collected at 15-min intervals throughout the experiment. Ghrelin infusion increased plasma ghrelin levels 2.9-fold of baseline. Ghrelin significantly decreased LH pulse frequency (from 0.89 +/- 0.07/h in baseline to 0.57 +/- 0.10/h during ghrelin infusion; P < 0.05, mean +/- sem), whereas LH pulse frequency remained unchanged during saline treatment. LH pulse amplitude was not affected. Ghrelin also significantly stimulated both cortisol and GH release, but had no effect on leptin. We conclude that ghrelin can inhibit GnRH pulse activity and may thereby mediate the suppression of the reproductive system observed in conditions of undernutrition, such as in anorexia nervosa. Ghrelin also activates the adrenal axis, but the relevance of this to the inhibition of GnRH pulse frequency remains to be established.
Vulliémoz
Nicolas R
NR
Department of Obstetrics and Gynecology, College of Physicians & Surgeons, Columbia University, 630 West 168th Street, New York, New York 10032, USA.
Xiao
Ennian
E
Xia-Zhang
Linna
L
Germond
Marc
M
Rivier
Jean
J
Ferin
Michel
M
D054369:Agouti-Related Protein; D000818:Animals; D005260:Female; D054439:Ghrelin; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D036341:Intercellular Signaling Peptides and Proteins; D007986:Luteinizing Hormone / Q000097:blood*; D008253:Macaca mulatta; D009478:Neuropeptide Y / Q000096:biosynthesis; D010052:Ovariectomy; D036361:Peptide Hormones / Q000494:pharmacology*; D010913:Pituitary-Adrenal System / Q000187:drug effects; D011506:Proteins / Q000378:metabolism
D054369:Agouti-Related Protein; D054439:Ghrelin; D036341:Intercellular Signaling Peptides and Proteins; D009478:Neuropeptide Y; D036361:Peptide Hormones; D011506:Proteins; D007986:Luteinizing Hormone