The present study was carried out to investigate the effects of acute administration of the soluble glucocorticoid receptor agonist, decadron phosphate (DEC, dexamethasone sodium phosphate), on pituitary luteinizing hormone (LH) release in intact adult male rats. DEC was administered intravenously to individual groups of animals at a dose of either 0.05 or 0.5 mg DEC/kg, and the magnitude and time course of drug-induced alterations in plasma LH concentrations were evaluated. DEC was observed to elicit a dose-proportionate decrease in plasma LH within hours after systemic injection. Both doses of DEC significantly reduced the magnitude of exogenous LH-releasing hormone (RH; 10 ng/100 g b.w.)-induced increases in plasma LH at time points coincident with drug-induced decreases in basal LH release. During in vitro perifusion of isolated anterior pituitary tissue fragments, the administration of DEC, via the perifusate, at a concentration of 1.0 microgram/ml had no impact upon basal LH release, but did effectively diminish LHRH-stimulated hormone release from perifused tissues. Intracerebroventricular injection of DEC also resulted in a decline in circulating LH. While intracerebroventricular (ICV) administration of 10 ng of DEC had no impact upon circulating LH, higher doses of 100 ng and 1.0 micrograms significantly depressed circulating LH levels in a dose-related manner. Both of these ICV doses were also found to diminish pituitary responsiveness to LHRH. Lastly, DEC was intravenously administered at a dose of 0.5 mg/kg to groups of orchidectomized and orchidectomized, testosterone (T)-treated male rats.(ABSTRACT TRUNCATED AT 250 WORDS)