Characterization of a gonadotropin-releasing hormone receptor site in term placenta and chorionic villi.
The properties of GnRH receptor sites in the human placenta were analyzed by binding studies performed in particulate and solubilized receptor preparations. The binding affinities (Ka) of the membrane receptor of term placenta for the GnRH superagonists [D-Lys6]- and [D-Ala6]des-Gly10- GnRH-N-ethylamide were 1.6 X 10(6) and 5.4 X 10(5) M-1, respectively. The binding affinities of native GnRH and a potent GnRH antagonist were similar to those of the superagonists (1.1 and 2.0 X 10(6) M-1, respectively). The placental sites could be solubilized by extraction with the detergent 3-[(3-cholamidopropyl) dimethylammonio] 1-propane sulfonate, with retention of 40-45% of the specific binding activity, though with a significant decrease in binding affinity. The sites were also solubilized with sodium dodecyl sulfate after covalent labeling with a photoreactive 125I-labeled [D-Lys6] GnRH agonist derivative. Analysis of the solubilized hormone-receptor complex on polyacrylamide gradient gels showed a single band of 53,700 mol wt, similar to the mol wt of the pituitary GnRH receptor in other species. It is clear that the placental receptor differs markedly from the GnRH receptor of the pituitary gland in its low binding affinity and lack of selectivity for GnRH analogs. However, it is possible that the human placental receptor for GnRH could serve as a low affinity regulatory site for locally formed GnRH or related low affinity regulatory site for locally formed GnRH or related peptides within the placenta, and that the placental GnRH system has a significant role in the maintenance of pregnancy.
D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism; D002823:Chorion / Q000378:metabolism*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008871:Microvilli / Q000378:metabolism*; D008970:Molecular Weight; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011956:Receptors, Cell Surface / Q000302:isolation & purification / Q000378:metabolism*; D011966:Receptors, LHRH; D013379:Substrate Specificity
D011956:Receptors, Cell Surface; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone