Signal transduction characteristics of the corticotropin-releasing hormonereceptors in the feto-placental unit

Placentally derived CRH plays a major role in the mechanisms controlling hu man pregnancy and parturition. In this study, we sought to investigate the signal transduction mechanisms of CRH Type-1 receptors in the fete-placenta l unit. To clarify the signal transduction components in placenta and fetal membranes, we investigated the expression of G proteins and adenylate cycl ase. Using the nonhydrolysable photoreactive analog [alpha-P-32] GTP-azidoanilid e and peptide antisera raised against G protein alpha-subunits, we studied coupling of CRH receptors to G proteins in both placental and fetal membran es. Treatment of placental membranes with human CRH (100 nM) increased the labeling of Gq, Go, and Gz but not Gi and Ga. Treatment of fetal membranes with human CRH (100 nM) increased the labeling of Go and Gq but not Gi, Gs, and Gz. These results were supported by experiments that showed that CRH f ailed to activate adenylate cyclase in these tissues, but induced an increa se in inositol phosphates instead. These findings provide new insights into the components of the signal transduction machinery in both fetal and plac ental membranes and suggest that CRH Type-1 receptors can couple to differe nt G proteins in different tissues. The physiological significance of these observations remains to be elucidated.