Expression of functional human chorionic gonadotropin/human luteinizing hormone receptor gene in human uterine arteries.

Abstract

The present study investigated 1) whether extra- and intramyometrial arteries contain hCG/human LH receptor messenger ribonucleic acid (mRNA) and receptor protein, 2) whether hCG can bind to its vascular receptors and regulate the formation of vasoactive eicosanoids, and 3) whether hCG administration for ovulation induction can affect the vascular resistance in uterine arteries. The uterine arteries contain multiple hCG/LH receptor mRNA transcripts in endothelial and smooth muscle cells. The uterine arteries also contain an 80-kilodalton immunoreactive receptor protein in endothelial and smooth muscle cells. The extra- and intramyometrial arteries and an 80-kilodalton receptor protein bind [125I]hCG, which is inhibited by excess unlabeled hCG. The receptor mRNA, receptor protein, and ligand binding are higher in smaller intramyometrial arteries than in larger extramyometrial arteries. Incubation of uterine arteries with highly purified hCG resulted in a dose-dependent increase in immunoreactive cyclooxygenase-1, cyclooxygenase-2, prostacyclin synthase, and 6-keto-prostaglandin-F1 alpha and a decrease in prostaglandin-E2, thromboxane-A2 synthase, and thromboxane-B2. There was a significant decrease in the resistance index in uterine arteries, but not in common carotid arteries, by 16 h after the administration of 10,000 IU hCG for ovulation induction in women. This decrease is positively correlated with serum hCG levels, but not with progesterone or estradiol levels. In summary, these data, demonstrating the expression of functional hCG/LH receptors in human uterine arteries, are novel and may have important implications for physiological uterine blood flow regulation, reproductive failure, and obstetrical hemorrhage.