DIRECT REGULATION OF HUMAN MYOMETRIAL CONTRACTIONS BY HUMAN CHORIONIC-GONADOTROPIN

Our laboratory previously demonstrated that the human myometrium conta ins functional hCG/LH receptors. The present study investigated whethe r hCG can directly regulate oxytocin-stimulated human myometrial contr actions. Uterine specimens were obtained from 30- to 40-yr-old women u ndergoing hysterectomy for leiomyomata, metrorrhagia, or prolapse. Myo metrial strips from the lower uterine segment were primed for 24 h wit h 2.2 nmol/L estradiol. Then, the slices were incubated for 4 h at 37 C with or without 10 nmol/L hCG and stimulated with 1 mu mol/L oxytoci n, and the contractions were measured. The results showed that hCG inh ibited the amplitude while paradoxically increasing the frequency of c ontractions. The effect of hCG was seen in proliferative, but not secr etory, phase myometrial specimens. hCG had no effect on rat hepatic po stal vein smooth muscle contractions, suggesting that the hCG action w as tissue specific. Oxytocin treatment of human myometrial smooth musc le cells resulted in a dose-dependent increase in intracellular free C a2+ levels. Pretreatment with hCG resulted in an attenuation of the ox ytocin response, suggesting that the action of hCG was mediated by dec reasing intracellular free Ca2+ levels. In summary, our results demons trate that hCG can directly inhibit the amplitude of oxytocin-stimulat ed contractions of human myometria from the proliferative phase of the cycle. The hCG action is tissue specific and appears to be mediated b y decreasing intracellular free Ca2+ levels in myometrial smooth muscl e cells.