FUNCTIONAL-CHARACTERIZATION OF THE ALTERNATIVELY SPLICED, PLACENTAL HUMAN GROWTH-HORMONE RECEPTOR

The human growth hormone family of peptide hormones is encoded by five genes, pituitary growth hormone (hGH-N), and four placentally express ed genes, growth hormone variant (hGH-V), chorionic somatomammotropin A and B (hCS-A, hCS-B), and prolactin (hPrl). As part of an effort to define the local effects of the placentally expressed members of the G H/Prl family of hormones on the placenta, we have identified an isofor m (hGHRd3) of the growth hormone receptor expressed in the placental v illi. hGHRd3 mRNA differs from the liver GHR mRNA by the deletion of a 66-base pair segment encoding exon 3. In this study we show that hGHR d3 mRNA encodes a stable and functional receptor. hGHRd3 mRNA is effic iently translated and processed in a rabbit reticulocyte lysate transl ation system as well as in an in vivo Xenopus laevis oocyte expression system. In Xenopus oocytes hGHRd3 is stably integrated into the cell membrane and binds and internalizes ligand as efficiently as hGHR. hGH Rd3 binds all three of the placentally expressed members of the GH/Prl gene family (hGH-V, hCS, and Prl) as well as both the 22 and 20 kDa i soforms of the pituitary hGH-N. The results of the present study stron gly support the expression of a functional hGHRd3 isoreceptor in the p lacenta which may serve in autocrine, paracrine, and/or endocrine acti vation.