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 ovariec-tomized rhesus monkeys, pretreated with dexamethasone (DEX; 1.5 mgb.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 < 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. Gonadotropin secretion declined, with maximal suppression seen by hour 3: LH and FSH were 37.1 (± 5.3) and 67.2% (± 4.8) (p < 0.01 vs. saline or CRH in DEX-treated animals). Cortisol concentrations were suppressed following DEX pretreatment, and neither CRH or morphine increased cortisol. In 3 animals, GnRH (2 pulses of 10 ug) was administered 2 h after morphine; this resulted in a rapid increase in LH release. We conclude that dexamethasone pretreatment prevents the inhibitory action of CRH on gonadotropin release as well. It may be postulated that this results from the failure of endogenous opioid peptide release; indeed, the persistence of the inhibitory action of morphine in DEX-pretreated monkeys indicates that glucocorticoids do not prevent opiate-receptor interactions. Furthermore, the effectiveness of GnRH to prevent the inhibitory action of morphine in these animals suggests that the opiod induced inhibition of LH is mediated centrally, through the inhibition of GnRH release.