Placental progesterone, prostaglandins and mechanisms leading to initiation of parturition in the human.
Present knowledge allows the identification of some features of the initiation of human parturition. Progesterone reduces myometrial sensitivity to labour-inducing agents. It suppresses gap junction formation and facilitates beta-adrenergic receptor expression by the myometrium which, in turn, exerts a positive feedback by enhancing beta-adrenergic-induced increases in placental progesterone production. Inhibition of gestagen action does not result in immediate initiation of labor but sensitises myometrial cells to contraction-inducing agents. Estrogens, in contrast, enable the myometrium to prepare for parturition by inducing oxytocin receptors and this seems to be the first step towards parturition. Coordinated myometrial contractions are facilitated by the increased gap junctions due to the estrogen drive. Absence of estrogen will result in failed parturition. The myometrium seems to be sensitised to oxytocin by placental CRF. Myometrial CRF receptors increase their avidity for CRF with ongoing pregnancy. Oxytocin evokes a variety of auto- and paracrine events which culminate in increased free intracellular calcium and the consequent contractions. In this cascade, prostaglandins can be identified as positive feedback agents, as they further enhance estrogen-induced expression of oxytocin receptors. Another second messenger of oxytocin action are the inositol phosphates which can further increase free intracellular calcium concentrations. Finally, endothelin-1, derived from endometrium and decidua, under oxytocin control, may serve as a myometrial contractor following delivery when oxytocin concentrations decline but when a strong myometrial contraction is needed to prevent large blood loss during and after placenta expulsion.
Neulen
J
J
University of Freiburg, Dept. of Obstet. Gynecol., Germany.
Breckwoldt
M
M
D005260:Female; D006728:Hormones / Q000502:physiology; D006801:Humans; D007745:Labor Onset / Q000502:physiology*; D010920:Placenta / Q000502:physiology*; D011247:Pregnancy; D011374:Progesterone / Q000502:physiology*; D011453:Prostaglandins / Q000502:physiology*
D006728:Hormones; D011453:Prostaglandins; D011374:Progesterone