Identification and characterization of a corticotrophin-releasing hormone receptor in human placenta.
Corticotrophin-releasing hormone (CRH) causes vasodilatation in the human fetal-placental circulation and has paracrine actions in placental tissue, suggesting that CRH receptors may be present in the human placenta. We have now identified and characterized placental CRH binding sites and compared them to those described previously in human myometrium and rat pituitary. Radiolabelled ovine CRH binding to placental membranes was pH-, time-, temperature- and divalent cation-dependent and was reversible in the presence of 1 mumol/l unlabelled ovine CRH. Scatchard analysis of placentae delivered vaginally or by elective caesarean section revealed dissociation constants (Kd) of 214.5 +/- 84 pmol/l (N = 8) and 45.4 +/- 23.9 pmol/l (N = 9), respectively. The Kd for caesarean placental binding sites was similar to that of human myometrium (59.6 pmol/l, N = 3) and rat pituitary (82.5 pmol/l, N = 3) receptors. However, in vaginally delivered placentae the CRH binding sites had a much lower affinity (p < 0.05). The receptor densities (Bmax) of vaginally delivered and caesarean-delivered placentae were 28.6 +/- 9.6 and 6.1 +/- 2.8 fmol/mg, respectively (p < 0.05). Chemical cross-linking studies using disuccinimidyl suberate indicated that the molecular weight of the CRH receptor in the placenta and rat pituitary is 75 kD. We conclude that there is a high-affinity population of CRH binding sites in the human placenta that are physicochemically similar to pituitary and myometrial CRH receptors. The CRH receptor properties in the placenta change in response to labour, when CRH levels in maternal blood are highest, suggesting that placental CRH may regulate its receptor.
Clifton
V L
VL
Maternal Health Research Center, Faculty of Medicine and Health Sciences, University of Newcastle, NSW, Australia.
Owens
P C
PC
Robinson
P J
PJ
Smith
R
R
D000293:Adolescent; D000328:Adult; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007457:Iodine Radioisotopes; D007743:Labor, Obstetric / Q000378:metabolism; D008297:Male; D008970:Molecular Weight; D009215:Myometrium / Q000737:chemistry / Q000648:ultrastructure; D010902:Pituitary Gland / Q000737:chemistry / Q000648:ultrastructure; D010920:Placenta / Q000737:chemistry* / Q000648:ultrastructure; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000032:analysis* / Q000378:metabolism; D013696:Temperature
D007457:Iodine Radioisotopes; D011257:Pregnancy Proteins; D018019:Receptors, Corticotropin-Releasing Hormone; D003346:Corticotropin-Releasing Hormone