IDENTIFICATION AND CHARACTERIZATION OF A CORTICOTROPIN-RELEASING HORMONE-RECEPTOR IN HUMAN PLACENTA

Corticotrophin-releasing hormone (CRH) causes vasodilatation in the hu man fetal-placental circulation and has paracrine actions in placental tissue, suggesting that CRH receptors may be present in the human pla centa. We have now identified and characterized placental CRH binding sites and compared them to those described previously in human myometr ium and rat pituitary. Radiolabelled ovine CRH binding to placental me mbranes was pH-, time-, temperature- and divalent cation-dependent and was reversible in the presence of 1 mu mol/l unlabelled ovine CRH. Sc atchard analysis of placentae delivered vaginally or by elective caesa rean section revealed dissociation constants (K-d) of 214.5+/-84 pmol/ l (N = 8) and 45.4+/-23.9 pmol/l (N = 9), respectively. The K-d for ca esarean placental binding sites was similar to that of human myometriu m (59.6 pmol/l, N = 3) and rat pituitary (82.5 pmol/l, N = 3) receptor s. However, in vaginally delivered placentae the CRH binding sites had a much lower affinity (p < 0.05). The receptor densities (B-max) of v aginally delivered and caesarean-delivered placentae were 28.6+/-9.6 a nd 6.1+/-2.8 fmol/mg, respectively (p < 0.05). Chemical cross-linlsing studies using disuccinimidyl suberate indicated that the molecular we ight of the CRH receptor in the placenta and rat pituitary is 75 kD. W e conclude that there is a high-affinity population of CRH binding sit es in the human placenta that are physicochemically similar to pituita ry and myometrial CRH receptors. The CRH receptor properties in the pl acenta change in response to labour, when CRH levels in maternal blood are highest, suggesting that placental CRH may regulate its receptor.