Astressin B, a nonselective corticotropin-releasing hormone receptor antagonist, prevents the inhibitory effect of ghrelin on luteinizing hormone pulse frequency in the ovariectomized rhesus monkey.
Administration of ghrelin, a key peptide in the regulation of energy homeostasis, has been shown to decrease LH pulse frequency while concomitantly elevating cortisol levels. Because increased endogenous CRH release in stress is associated with an inhibition of reproductive function, we have tested here whether the pulsatile LH decrease after ghrelin may reflect an activated hypothalamic-pituitary-adrenal axis and be prevented by a CRH antagonist. After a 3-h baseline LH pulse frequency monitoring, five adult ovariectomized rhesus monkeys received a 5-h saline (protocol 1) or ghrelin (100-microg bolus followed by 100 microg/h, protocol 2) infusion. In protocols 3 and 4, animals were given astressin B, a nonspecific CRH receptor antagonist (0.45 mg/kg im) 90 min before ghrelin or saline infusion. Blood samples were taken every 15 min for LH measurements, whereas cortisol and GH were measured every 45 min. Mean LH pulse frequency during the 5-h ghrelin infusion was significantly lower than in all other treatments (P < 0.05) and when compared with the baseline period (P < 0.05). Pretreatment with astressin B prevented the decrease. Ghrelin stimulated cortisol and GH secretion, whereas astressin B pretreatment prevented the cortisol, but not the GH, release. Our data indicate that CRH release mediates the inhibitory effect of ghrelin on LH pulse frequency and suggest that the inhibitory impact of an insufficient energy balance on reproductive function may in part be mediated by the hypothalamic-pituitary-adrenal axis.
Department of Obstetrics and Gynecology, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, New York 10032, USA.
Nicolas R
NR
Vulliémoz
Ennian
E
Xiao
Linna
L
Xia-Zhang
Jean
J
Rivier
Michel
M
Ferin
D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism / Q000494:pharmacology*; D004734:Energy Metabolism; D005260:Female; D054439:Ghrelin / Q000502:physiology*; D013006:Growth Hormone / Q000097:blood; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D007986:Luteinizing Hormone / Q000097:blood*; D008253:Macaca mulatta; D010052:Ovariectomy; D010446:Peptide Fragments / Q000494:pharmacology*; D010913:Pituitary-Adrenal System / Q000502:physiology; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D012098:Reproduction / Q000187:drug effects
D054439:Ghrelin; D010446:Peptide Fragments; D018019:Receptors, Corticotropin-Releasing Hormone; C120841:astressin B; D007986:Luteinizing Hormone; D013006:Growth Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone