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 intact rats. While the pituitary-adrenal axis is capable of discrimination between stressors of graded intensity, the effects of variable glucocorticoid output on the direction and magnitude of LH release during stress remain unclear. The present studies compared the effects of a psychological stress and two different physical stressors on peripheral corticosterone (CORT) and LH concentrations. Plasma CORT levels were elevated during each stress, but this increase in hormone release was significantly greater in response to physical stress. This differential CORT sensitivity to psychological vs. physical stress was correlated with divergent patterns of pituitary LH release; novel environment (NE) stress resulted in a transient increase in plasma LH, whereas both physical 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 studies showed that stimulation of GRs prior to stress with the potent ligand, dexamethasone (DEX), blunted the stimulatory effects of NE stress on circulating LH. Additional experiments investigated whether prolonged exposure to elevated glucocorticoid levels elicits adaptive responses from the hypothalamic-pituitary LH axis to acute stress. Chronic DEX administration resulted in a significant attenuation of the inhibitory LH response to acute immobilization, but had no impact upon the facilatory effects of NE stress on LH release. The current studies confirm previous reports of variation in the magnitude of CORT secretion elicited by stressors of different intensity, and provide new evidence that inhibitory patterns of pituitary LH release may be correlated with a high degree of activation of the pituitary-adrenal axis. Attenuation of the facilatory effects of novel environment stress on LH release by pretreatment with the GR agonist, DEX, suggests that GR-induced inhibition of LH requires occupation of GRs beyond that which occurs during this mild stressor. The present findings that stress-induced decreases in plasma LH are blunted by chronic glucocorticoid exposure support a role for glucocorticoid-dependent mechanisms in adaptation of GR-mediated inhibitory responses to stress.