Antagonism of type II, but not type I glucocorticoid receptors results in elevated basal luteinizing hormone release in male rats.

Abstract

The present studies utilized a pharmacologic approach to evaluate the role of corticosterone-preferring mineralocorticoid receptors (type I or MR) versus classic glucocorticoid receptors (type II or GR) in the regulation of basal pituitary luteinizing hormone (LH) secretion in vivo in male rats. Animals bearing indwelling intracardiac venous catheters received a subcutaneous (s.c.) injection of either vehicle, the MR antagonist, RU 752 (0.5 or 5.0 mg/kg body weight), or the GR antagonist, RU 486 (0.5 or 5.0 mg/kg body weight). Additional groups of rats were implanted with indwelling intracerebroventricular (i.c.v.) cannulas and intravenous catheters for drug administration and blood withdrawal, respectively, and injected i.c.v. with vehicle or graded doses (0.1, 1.0 or 10.0 micrograms/rat) of RU 752 or RU 486. The MR RU 752 failed to alter plasma LH concentrations regardless of dose or route of administration. In contrast, the GR antagonist, RU 486, elicited significant, dose-dependent increases in circulating LH when given either s.c. or i.c.v. Animals injected s.c. with either 0.5 or 5.0 mg RU 486/kg body weight showed elevated plasma LH levels; while the magnitude of this secretory response was not different between the two drug-treated groups, hormone levels remained elevated over baseline for a longer period of time in rats given the higher dose. Central administration of RU 486 at a dose of either 1.0 or 10.0 micrograms also resulted in elevated LH release; both the magnitude and duration of this increase in plasma LH were dose-dependent. In additional experiments, groups of rats were pretreated with vehicle or the synthetic GR agonist, RU 362, before administration of RU 486.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: K P Briski, P W Sylvester
• Journal: Neuroendocrinology (Neuroendocrinology) Vol. 60 Issue 6 Pg. 601-8 (Dec 1994) ISSN: 0028-3835 [Print] Switzerland
• PMID: 7700503 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Androstanols
• Glucocorticoids
• Mineralocorticoid Receptor Antagonists
• Receptors, Glucocorticoid
• Mifepristone
• 3'-(3-oxo-11 beta,17-dihydroxy-4-androstene-17 alpha- yl)propionic acid lactone
• 11,17-dihydroxy-6-methyl-17-(1-propynyl)androsta-1,4,6-triene-3-one
• Canrenone
• Luteinizing Hormone

Topics

• Androstanols (pharmacology)
• Animals
• Canrenone (analogs & derivatives, pharmacology)
• Glucocorticoids (metabolism, physiology)
• Luteinizing Hormone (blood, metabolism)
• Male
• Mifepristone (administration & dosage, pharmacology)
• Mineralocorticoid Receptor Antagonists
• Rats
• Rats, Sprague-Dawley
• Receptors, Glucocorticoid (agonists, antagonists & inhibitors)