Effects of peripheral versus central administration of the endogenous glucocorticoid, corticosterone, and the glucocorticoid receptor agonist, RU 28362, on LH release in male rats.
The current studies evaluated the effects of the synthetic glucocorticoid receptor (GR) agonist, RU 28362, and the endogenous, non-selective receptor ligand, corticosterone (Cort), on pituitary luteinizing hormone (LH) secretion in male rats. Steroids were injected subcutaneously (s.c.) in animals previously implanted with intracardiac venous catheters, or administered intracerebroventricularly (i.c.v.) to other groups of animals. A dose-proportionate decrease in plasma LH was observed following either s.c. or i.c.v. administration of RU 28362; pretreatment with the GR antagonist, RU 38486, blunted the inhibitory impact of RU 28362 on circulating LH. In other experiments, s.c. injection of Cort elicited divergent, dose-dependent patterns of LH release. While the lowest peripheral dose (0.25 mg Cort/kg) promoted a transient elevation in plasma LH, higher doses exerted a progressively greater inhibitory effect on hormone release. The suppressive effects of the highest s.c. dose (2.5 mg Cort/kg) were reversed by pretreatment with the RU 38486, but not by the mineralocorticoid receptor antagonist, RU 26752. Plasma LH levels were transiently elevated following i.c.v. administration of graded doses of Cort. The lowest dose (0.1 microgram Cort/rat) only facilitated LH release, but higher doses (1.0 and 10.0 micrograms/animal) elicited a biphasic LH response, which was characterized by an initial elevation, then subsequent reduction in plasma LH below preinjection baseline levels. Prior administration of the mineralocorticoid receptor antagonist, RU 26752, attenuated the stimulatory impact of i.c.v. Cort on LH release, while both RU 26752 and RU 38486 reversed the secondary decline in plasma LH.(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.
D000732:Androstanols / Q000494:pharmacology*; D000818:Animals; D003345:Corticosterone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007278:Injections, Spinal; D007279:Injections, Subcutaneous; D007986:Luteinizing Hormone / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000819:agonists / Q000502:physiology
D000732:Androstanols; D011965:Receptors, Glucocorticoid; C049154:11,17-dihydroxy-6-methyl-17-(1-propynyl)androsta-1,4,6-triene-3-one; D007986:Luteinizing Hormone; D003345:Corticosterone