PLACENTAL PROGESTERONE, PROSTAGLANDINS AND MECHANISMS LEADING TO INITIATION OF PARTURITION IN THE HUMAN

Present knowledge allows the identification of some features of the in itiation of human parturition. Progesterone reduces myometrial sensiti vity to labour-inducing agents. It suppresses gap junction formation a nd facilitates beta-adrenergic receptor expression by the myometrium w hich, 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 indu cing oxytocin receptors and this seems to be the first step towards pa rturition. 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 sensiti sed to oxytocin by placental CRE Myometrial CRF receptors increase the ir avidity for CRF with ongoing pregnancy. Oxytocin evokes a variety o f auto- and paracrine events which culminate in increased free intrace llular calcium and the consequent contractions. In this cascade, prost aglandins can be identified as positive feedback agents, as they furth er 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. Finall y, 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 contracti on is needed to prevent large blood loss during and after placenta exp ulsion.