Antiestrogenic effect of opioid peptides in rat uterus

The effects of a single injection or continuous infusion of opioid peptide, [D-Met(2),pro(5)]enkephalinamide (ENK) on the hormone binding and transcri ptional properties of estrogen receptors were investigated in estradiol (E- 2) treated rat uterus. The level of estrogen- (ER) and progesterone recepto r (PR) proteins, the hormone binding of E-2 receptors and the effects of si ngle injection of ENK with or without naltrexone (NAL) on the E-2-induced c hanges in the level of Fos and Jun proteins and the binding of AP-1 protein s to DNA were studied. The receptor proteins levels were determined by West ern blots and the binding of AP-1 to DNA by electrophoretic mobility shift assay. Both the ER and PR protein concentrations and the [H-3]Estradiol bin ding to the high affinity nuclear receptors decreased after ENK treatment d uring the first two days. At 72 h the PR concentration decreased further, w hile no significant changes were found in the level of ER, however, at this time the former competitive E-2 binding turned into positive cooperativity . The E-2-induced increase in the level of Fos proteins and the binding of AP-1 proteins to DNA was inhibited by a single injection of ENK. We conclud e that the endogenous opioid peptides may interact with E-2 in the gene reg ulation of rat uterus. (C) 2000 Elsevier Science Ltd. All rights reserved.