Dexamethasone treatment prevents the inhibitory effect of corticotropin-releasing hormone on gonadotropin release in the primate.
Corticotropin-releasing hormone (CRH) has been shown to inhibit gonadotropin secretion and this effect is mediated by endogenous opioid peptides, presumably stimulated by CRH. Since glucocorticoids are known to block the CRH-induced ACTH response, it can be hypothesized that by concurrently preventing endogenous opioid peptide release, they would also prevent the inhibitory action of CRH on gonadotropin secretion. We tested this hypothesis in 4 ovariectomized rhesus monkeys, pretreated with dexamethasone (DEX; 1.5 mg b.i.d. for 5 days). In experiment 1, the effects of a 5 h i.v. hCRH infusion with or without DEX pretreatment and of physiological saline were compared. Blood samples were taken at 15-min intervals during a 3 hour preinfusion control and throughout the infusion. Sera were assayed for luteinizing hormone (LH), follicle-stimulating hormone (FSH) and cortisol by RIA. In the absence of DEX pretreatment, LH and FSH levels were progressively decreased during the CRH infusion: by hour 5, LH and FSH areas under the curve were 34.1 ( +/- 7.6) and 65.3% ( +/- 2.5) (mean % of preinfusion control values; + SE), respectively (p less than 0.01 vs. saline). In contrast, DEX pretreatment prevented the CRH-induced gonadotropin decrease: by hour 5, LH and FSH areas under the curve were 91.9 ( +/- 9.0) and 99.0% ( +/- 5.7) (n.s. vs. saline). In experiment 2, we tested whether DEX-treated monkeys would remain responsive to the gonadotropin inhibitory action of an opiate agonist. After a 3 hour preinfusion control baseline, morphine (9 mg i.v.) was given as a bolus injection to the same 4 animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Gindoff
P R
PR
Department of Obstetrics and Gynecology, College of Physicians and Surgeons, Columbia University, New York, N.Y.
Xiao
E N
EN
Luckhaus
J
J
Ferin
M
M
D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D005640:Follicle Stimulating Hormone / Q000097:blood / Q000378:metabolism*; D007262:Infusions, Intravenous; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism*; D008253:Macaca mulatta; D009020:Morphine / Q000494:pharmacology; D012016:Reference Values
D009020:Morphine; D003907:Dexamethasone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D003346:Corticotropin-Releasing Hormone