STIMULATORY VS INHIBITORY EFFECTS OF ACUTE STRESS ON PLASMA-LH - DIFFERENTIAL-EFFECTS OF PRETREATMENT WITH DEXAMETHASONE OR THE STEROID-RECEPTOR ANTAGONIST, RU-486

Acute stress elicits variable patterns of pituitary LH release in inta ct rats. While the pituitary-adrenal axis is capable of discrimination between stressors of graded intensity, the effects of variable glucoc orticoid output on the direction and magnitude of LH release during st ress remain unclear. The present studies compared the effects of a psy chological stress and two different physical stressors on peripheral c orticosterone (CORT) and LH concentrations. Plasma CORT levels were el evated during each stress, but this increase in hormone release was si gnificantly greater in response to physical stress. This differential CORT sensitivity to psychological vs. physical stress was correlated w ith divergent patterns of pituitary LH release; novel environment (NE) stress resulted in a transient increase in plasma LH, whereas both ph ysical stressors ultimately caused a reduction in circulating hormone levels. Pretreatment with the glucocorticoid receptor (GR) antagonist, RU 486, reversed physical stress-induced decreases in LH release, but did not further facilitate circulating LH during NE stress. Other stu dies showed that stimulation of GRs prior to stress with the potent li gand, dexamethasone (DEX), blunted the stimulatory effects of NE stres s on circulating LH. Additional experiments investigated whether prolo nged exposure to elevated glucocorticoid levels elicits adaptive respo nses from the hypothalamic-pituitary LH axis to acute stress. Chronic DEX administration resulted in a significant attenuation of the inhibi tory LH response to acute immobilization, but had no impact upon the f acilatory effects of NE stress on LH release. The current studies conf irm previous reports of variation in the magnitude of CORT secretion e licited by stressors of different intensity, and provide new evidence that inhibitory patterns of pituitary LH release may be correlated wit h a high degree of activation of the pituitary-adrenal axis. Attenuati on of the facilatory effects of novel environment stress on LH release by pretreatment with the CR agonist, DEX, suggests that GR-induced in hibition of LH requires occupation of GRs beyond that which occurs dur ing this mild stressor. The present findings that stress-induced decre ases in plasma LH are blunted by chronic glucocorticoid exposure suppo rt a role for glucocorticoid-dependent mechanisms in adaptation of GR- mediated inhibitory responses to stress.