The antiglucocorticoid, RU486, attenuates stress-induced decreases in plasma-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 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 intracerebroventricular (icv) administration of RU486 (10.0 micrograms/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 pretreated 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. In summary, the present findings that pharmacologic antagonism of GR attenuates acute and chronic stress-induced inhibition of circulating LH support a role for glucocorticoids in mechanisms underlying suppression of pituitary LH release during stress.(ABSTRACT TRUNCATED AT 250 WORDS)
Briski
K P
KP
Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology, College of Veterinary Medicine, Washington State University, Pullman 99164-6520, USA.
Vogel
K L
KL
McIntyre
A R
AR
D000818:Animals; D007103:Immobilization; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D007986:Luteinizing Hormone / Q000097:blood*; D008297:Male; D015735:Mifepristone / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000097:blood*
D015735:Mifepristone; D007986:Luteinizing Hormone