DECREASED EXPRESSION OF FUNCTIONAL HUMAN CHORIONIC-GONADOTROPIN LUTEINIZING-HORMONE RECEPTOR GENE IN HUMAN UTERINE LEIOMYOMAS

Human myometrium contains functional hCG/LH receptors. The purpose of this study was to determine whether or not leiomyomas that arise from myometrium also contain these receptors. Northern blotting demonstrated that leiomyomas and normal adjacent myometria contained hCG/LH receptor mRNA transcripts. Western immunoblotting showed that leiomyomas and corresponding normal myometria also contained 60- and 50-kDa receptor proteins. Ligand blotting revealed that only the 50-kDa receptor protein in leiomyomas and corresponding normal myometria could bind I-125-hCG and that this binding was inhibited by excess unlabeled hCG. In situ hybridization and immunocytochemistry revealed that smooth muscle cells in leiomyomas and corresponding normal myometria contained the hCG/LH receptor mRNA transcripts and receptor proteins. The receptor levels were lower in leiomyomas than in corresponding normal myometria. However, the receptors were functional, as treatment with hCG resulted in a decrease of connexin-43 protein levels in leiomyomas as in normal myometria. In summary, human uterine leiomyomas express a functional hCG/LH receptor gene at a reduced level compared with that for normal corresponding myometria, This finding could be relevant to an understanding of the growth control mechanisms in leiomyomas and the manner in which medical therapy for leiomyomas might work.