Direct regulation of human myometrial contractions by human chorionic gonadotropin.

Abstract

Our laboratory previously demonstrated that the human myometrium contains functional hCG/LH receptors. The present study investigated whether hCG can directly regulate oxytocin-stimulated human myometrial contractions. Uterine specimens were obtained from 30- to 40-yr-old women undergoing hysterectomy for leiomyomata, metrorrhagia, or prolapse. Myometrial strips from the lower uterine segment were primed for 24 h with 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 mumol/L oxytocin, and the contractions were measured. The results showed that hCG inhibited the amplitude while paradoxically increasing the frequency of contractions. The effect of hCG was seen in proliferative, but not secretory, phase myometrial specimens. hCG had no effect on rat hepatic portal vein smooth muscle contractions, suggesting that the hCG action was tissue specific. Oxytocin treatment of human myometrial smooth muscle cells resulted in a dose-dependent increase in intracellular free Ca2+ levels. Pretreatment with hCG resulted in an attenuation of the oxytocin response, suggesting that the action of hCG was mediated by decreasing intracellular free Ca2+ levels. In summary, our results demonstrate that hCG can directly inhibit the amplitude of oxytocin-stimulated contractions of human myometria from the proliferative phase of the cycle. The hCG action is tissue specific and appears to be mediated by decreasing intracellular free Ca2+ levels in myometrial smooth muscle cells.

Therapeutic Potential of Human Chorionic Gonadotropin Against Overactive Bladder

“…However, there are more data on human myometrium than rat detrusor muscle, and there are no data on human detrusor muscle. [46][47][48] The above-mentioned findings support that hCG and LH are continence hormones. However, their actions can lead to incontinence because the bladder that is unable to contract will not be able to empty when it is full.…”

“…Besides detrusor muscle, hCG can inhibit the contractions of myometrial smooth muscle and vascular smooth muscle in reproductive organs, which explains the minimal side effects. [45][46][47][48][68][69][70][71][72][73][74][75][76][77][78][79][80][81] There are still many unanswered scientific questions with regard to hCG in OAB. Some of the answers come from clinical trials and others from continued hCG research on bladder.…”

Human Chorionic Gonadotropin-Mediated Immune Responses That Facilitate Embryo Implantation and Placentation

“…However, although often neglected, r-hCG has a broader influence on fetal and maternal pathways allowing proper implantation and placentation. This includes the fusion of cytotrophoblast cells into the multinuclear structure of the syncytiotrophoblast (15), the formation of the umbilical circulation in villous tissue and the formation of the umbilical cord (16,17), the growth of fetal organs (18), the contribution to angiogenesis by forcing the development and growth of uSA (19)(20)(21) and the suppression of myometrial contractions (22). Thereby, hCG targets several molecules that are involved in decidualization, implantation, vascularization and tissue remodeling such as prolactin, insulinlike growth factor binding protein-1, macrophage colony stimulating factor, leukemia inhibitory factor (LIF), vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-9, tissue inhibitors of MMPs (TIMPs), galectin-3, and glycodelin (23)(24)(25)(26) (Figure 1B).…”

Why are We Waiting to Start Large Scale Clinical Testing of Human Chorionic Gonadotropin for the Treatment of Preterm Births?

“…7,12,15,16 One of these roles is an inhibition of myometrial contractions, which is central to the thesis of using hCG in the treatment of preterm births. [18][19][20] Moreover, the inhibition of myometrial contractions is a prerequisite for an initiation and maintenance of pregnancy, and its gradual easing allows myometrial stimulants to dominate and induce normal labor progression at the end of the pregnancy. [18][19][20][21] The hCG Receptors in Human Myometrium Human uterine hCG/LH receptors are present in endometrium, myometrium, and blood vessels, with more receptors in smaller intramyometrial vessels than in larger extramyometrial vessels.…”