Inhibition of glucose metabolism by progesterone in adipocytes: role of protein synthesis

Abstract

Progesterone decreases [1-14C]glucose oxidation in isolated female rat adipocytes within 20 min of incubation. Because steroids regulate transcription mechanisms, the relationship between protein synthesis and glucose metabolism was studied in the presence of progesterone. Actinomycin D does not affect basal glucose oxidation or the progesterone effects on it; cycloheximide and puromycin decrease basal glucose oxidation, but only puromycin decreases the inhibitory progesterone effect. Although puromycin inhibits glucose transport, the common site of action of puromycin and progesterone does not seem to be glucose transport, which, as we showed previously, is not modified by the steroid. Incorporation of [3H]leucine into acid-precipitable proteins is decreased by puromycin and cycloheximide but not by actinomycin D or progesterone; moreover, the action of these inhibitors does not change in the presence of the steroid. As shown by electrophoresis (SDS–PAGE) and autoradiography, L-leucine is incorporated into adipocyte proteins as early as 20 min and progesterone increases this incorporation into five proteins. Leucine is a ketogenic amino acid that is also incorporated into lipids; progesterone depresses L-leucine incorporation into fatty acids by a glucose-dependent mechanism. These results suggest that the inhibitory effect of progesterone on glucose metabolism is related to an enhanced protein synthesis counterbalanced by decreased fatty acid synthesis.Key words: adipocytes, glucose metabolism, progesterone, protein synthesis, gel autoradiography.