Progesterone and synthetic steroids produce insulin resistance at the post-receptor level in adipocytes of female rats

The effects of progesterone, its agonists (progestin RU-5020, glucocorticoid RU-26988) and antagonist (antiprogesterone, anti-glucocorticoid RU-486) were tested on isolated fat cells in vitro. When added to the incubation medium, all four steroids decreased basal glucose oxidation. The inhibitory ef...

Full description

Saved in:

Bibliographic Details
Published in:	Steroids Vol. 52; no. 5-6; p. 583
Main Authors:	Sutter-Dub, M T, Kaaya, A, Sfaxi, A l, Sodoyez-Goffaux, F, Sodoyez, J C, Sutter, B C
Format:	Journal Article
Language:	English
Published:	United States 01-11-1988
Subjects:	Adipose Tissue - cytology Adipose Tissue - drug effects Adipose Tissue - metabolism Androstanols - pharmacology Animals Dose-Response Relationship, Drug Estrenes - pharmacology Female Glucocorticoids - pharmacology Glucose - metabolism In Vitro Techniques Insulin - metabolism Insulin Resistance Mifepristone Ovariectomy Oxidation-Reduction Oxidative Phosphorylation Progesterone - antagonists & inhibitors Progesterone - pharmacology Progesterone - physiology Progesterone Congeners - pharmacology Rats Rats, Inbred Strains Receptor, Insulin - drug effects Receptor, Insulin - metabolism Time Factors
Online Access:	Get more information
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	The effects of progesterone, its agonists (progestin RU-5020, glucocorticoid RU-26988) and antagonist (antiprogesterone, anti-glucocorticoid RU-486) were tested on isolated fat cells in vitro. When added to the incubation medium, all four steroids decreased basal glucose oxidation. The inhibitory effect of the steroids appeared early (20 min incubation) and was sustained during a 2-h incubation. The early inhibitory effect was less marked for progesterone agonist RU-5020 than for the other three steroids. When incubation was prolonged for 2 h, the lowest inhibitory effect was observed with progesterone antagonist RU-486. Insulin-stimulated glucose oxidation was inhibited by progesterone, its antagonist RU-486, one of its agonists RU-26988, but not by the other agonist RU-5020. Analysis of the dose response curves showed that progesterone, RU-26988, and RU-486 decreased fat cells' responsiveness and, only for RU-486, sensitivity to insulin. Adipocytes isolated from ovariectomized, progesterone-treated rats showed a decreased maximal response to insulin and decreased insulin sensitivity in opposition to cells incubated directly with the steroid. No inhibition of 125I-labeled insulin binding was seen as an acute or chronic effect of progesterone. It is concluded that progesterone and the studied related steroids decrease glucose oxidation by mechanism(s) distal to insulin binding to its specific receptors.
ISSN:	0039-128X
DOI:	10.1016/0039-128X(88)90125-0