Expression of human chorionic gonadotropin (hCG)/luteinizing hormone receptors and regulation of the cyclooxygenase-1 gene by exogenous hCG in human fetal membranes.

Abstract

The present study characterized hCG/LH receptors from messenger ribonucleic acid (mRNA) to protein and whether exogenous hCG can bind and regulate the expression of the cyclooxygenase-1 (COX-1) gene in human fetal membranes from term pregnancy. Northern blotting showed that fetal membranes contain 6.0, 4.4, 2.4, and 1.4 kilobases of hCG/LH receptor mRNA transcripts. In situ hybridization revealed that amnion, chorion, and decidua contain receptor transcripts. Western immunoblotting and immunocytochemistry showed that amnion, chorion, and decidua also contain an 80-kDa receptor protein. Ligand blotting demonstrated that the 80-kDa receptor protein in fetal membranes can bind [125I]hCG, and this binding was inhibited by excess unlabeled hCG. Treatment of fetal membranes with highly purified hCG resulted in a dose- and time-dependent increase in immunoreactive COX-1 protein. The response of hCG was seen in all layers of fetal membranes. The treatment with hCG also resulted in an increase in steady state COX-1 mRNA levels. The action of hCG was prevented by cotreatment with H-89, an inhibitor of protein kinase A, but not by calphostin or lavendustin, which inhibit protein kinase C and tyrosine kinase, respectively. In summary, human fetal membranes contain hCG receptor transcripts and receptor protein that can bind hCG and up-regulate the expression of COX-1 gene.