SEX HORMONE-BINDING GLOBULIN STIMULATES CHORIONIC-GONADOTROPIN SECRETION FROM HUMAN CYTOTROPHOBLASTS IN CULTURE

The effects of sex hormone-binding globulin (SHBG) on the secretion of human chorionic gonadotrophin (HCG) and cAMP by cultured human cytotr ophoblasts were investigated. Cytotrophoblasts obtained from normal te rm placentae were cultured in serum-free medium with or without the ad dition of human SHBG, The presence of SHBG in the medium increased the release of HCG and the accumulation of cAMP, Ligand-free SHBG was abl e to raise both HCG and cAMP concentrations and the maximal response w as observed with 1 nM of the steroid-binding globulin, Addition of eit her oestradiol or 5 alpha-dihydrotestosterone (DHT) to cultures previo usly incubated with SHBG in a final molar ratio of 1:10 resulted in a further increase of HCG and cAMP concentrations. This effect was block ed when cultured placental cells were exposed to SHBG that was previou sly saturated with DHT or when incubated in the presence of steroids o nly. The results of the present study provide evidence for the in-vitr o regulation of HCG secretion by SHBG and further support the concept that this steroid-hinding protein may act as a mediator of steroid act ion at the cellular level, Finally, the increase in cAMP suggests that SHBG receptor located in the surface of syncytiotrophoblast membranes is coupled to adenylate cyclase as part of the G-protein receptor fam ily. Our results may provide new insights into the biological implicat ions of extracellular steroid-binding proteins as well as new perspect ives on the endocrinology of pregnancy.