The Antiglucocorticoid, RU486, Attenuates Stress-Induced Decreases in Plasma-Luteinizing Hormone Concentrations in Male Rats

Abstract

The present studies investigated the role of glucocorticoid receptors (GR) in the inhibitory effects of acute and chronic immobilization stress on pituitary luteinizing hormone (LH) release. Systemic administration of the GR antagonist, RU486, significantly attenuated the acute decline in circulating LH observed in intact male rats immobilized by encasement within paper cocoons. Whereas vehicle-injected controls exhibited a significant reduction in plasma LH between +1 and +5 h of stress, animals given subcutaneous (sc) injections of 2.5 mg RU846/kg did not exhibit a reduction in circulating LH until 4 h after initiation of stress. Plasma LH levels in the GR-treated group were significantly elevated compared to the vehicle controls between +1 and +3 h of stress. Repetitive exposure to the same stress stimulus 24 and 48 h later resulted in decreased plasma LH levels in the vehicle-treated rats, but not in the animals injected sc with RU486. Other studies showed that intracere-broventricular (icv) administration of RU486 (10.0 µg/rat) also blunted the inhibitory effects of acute and chronic immobilization stress on pituitary LH release. In experiments designed to evaluate whether activation of central GR can influence the magnitude and/or temporal characteristics of the LH secretory response to acute inhibitory stress, it was observed that animals pre-treated by icv injection of the GR agonist, RU362, exhibited a greater reduction in plasma LH levels during the first hour of stress, as compared to rats pretreated with vehicle alone.

Does the Type II Glucocorticoid Receptor Mediate Cortisol-Induced Suppression in Pituitary Responsiveness to Gonadotropin-Releasing Hormone?

“…Finally, it is of interest to consider our findings in light of evidence that RU486 attenuated the suppression of LH secretion in rats subjected to immobilization stress (52). Not only does that observation provide evidence that glucocorticoids are physiologically relevant to the suppression of gonadotropin secretion in response to this type of stress, it also implicates GR as the receptor mediating this response.…”

Does Cortisol Inhibit Pulsatile Luteinizing Hormone Secretion at the Hypothalamic or Pituitary Level?

“…Surprisingly, few studies have tested whether stress-induced inhibition of gonadotropin secretion can be attenuated by blocking glucocorticoid synthesis or action. The nonselective GR antagonist, RU486, attenuated LH inhibition during immobilization stress in gonadectomized male rats, suggesting a mediatory role of glucocorticoids in gonadotropin suppression (41). In contrast, blockade of increased cortisol synthesis during immune/inflammatory stress did not reverse the suppression of pulsatile GnRH and LH secretion in ovariectomized sheep (6).…”

Role of urocortin 2 secreted by the pituitary in the stress-induced suppression of luteinizing hormone secretion in rats

“…Therefore, ACTH does not seem to be involved in the mechanism by which Ucn 2 suppresses the secretion and expression of LH although ACTH released by CRF may inhibit LH secretion during stress. Glucocorticoids are reported to inhibit the LH response to GnRH in vivo and in vitro (5,6,26,34). However, because anti-Ucn 2 IgG blocked the stressinduced suppression of plasma LH and LH ␤-subunit mRNA expression without affecting POMC mRNA expression in the anterior and intermediate lobes, it would appear that the increase in corticosterone secretion induced by ACTH during immobilization stress does not play a major role in stressinduced suppression of LH secretion.…”