THE ANTIGLUCOCORTICOID, RU486, ATTENUATES STRESS-INDUCED DECREASES INPLASMA-LUTEINIZING HORMONE CONCENTRATIONS IN MALE-RATS

The present studies investigated the role of glucocorticoid receptors (GR) in the inhibitory effects of acute and chronic immobilization str ess on pituitary luteinizing hormone (LH) release. Systemic administra tion of the GR antagonist, RU486, significantly attenuated the acute d ecline in circulating LH observed in intact male rats immobilized by e ncasement within paper cocoons. Whereas vehicle-injected controls exhi bited a significant reduction in plasma LH between +1 and +5 h of stre ss, animals given subcutaneous (sc) injections of 2.5 mg RU846/kg did not exhibit a reduction in circulating LH until 4 h after initiation o f stress. Plasma LH levels in the GR-treated group were significantly elevated compared to the vehicle controls between +1 and +3 h of stres s. Repetitive exposure to the same stress stimulus 24 and 48 h later r esulted in decreased plasma LH levels in the vehicle-treated rats, but not in the animals injected sc with RU486. Other studies showed that intracerebroventricular (icv) administration of RU486 (10.0 mu g/rat) also blunted the inhibitory effects of acute and chronic immobilizatio n stress on pituitary LH release. In experiments designed to evaluate whether activation of central GR can influence the magnitude and/or te mporal characteristics of the LH secretory response to acute inhibitor y stress, it was observed that animals pre treated by icy injection of the GR agonist, RU362, exhibited a greater reduction in plasma LH lev els during the first hour of stress, as compared to rats pretreated wi th vehicle alone. In summary, the present findings that pharmacologic antagonism of GR attenuates acute and chronic stress-induced inhibitio n of circulating LH support a role for glucocorticoids in mechanisms u nderlying suppression of pituitary LH release during stress. The resul ts also suggest that inhibitory glucocorticoid effects observed under these physiologic conditions may be mediated, in part, by activation o f central GR. The present observations that exogenous stimulation of c entral GR potentiates the magnitude and onset of inhibitory patterns o f LH release during acute stress support the hypothesis that GR-depend ent neuroendocrine mechanisms are inhibitory to LH release during stre ss, and suggest that net suppression of circulating LH during stress m ay reflect the extent of GR occupation by endogenous glucocorticoids.