Cloning and characterization of a placentally expressed isoform of the human growth hormone receptor
Five members of the growth hormone/prolactin gene family are expressed in the human placenta: Human growth hormone variant (hGH-V), the chorionic somatomammotropins (hCS-A and hCS-B), and prolactin. In attempting to define the role of these hormones in placental development, I have structurally characterized the human placental growth hormone receptor mRNA which may mediate their local activity on placental growth and function. hGH receptor mRNAs were cloned from a placental cDNA library. One clone encompassed the entire hGH receptor coding region and is identical to the previously reported liver hGH receptor cDNA except for a precise deletion of 66 bp corresponding to exon 3 predicting a hGHR isoform that is identical to the liver hGH receptor except for a 22 residue deletion. The hGH receptor mRNAs in the placental villi are entirely of this exon 3 deleted type. An RT/PCR assay was used to further characterize GH receptor mRNA expression. hGH receptor mRNA was detected in all four tissues of the placenta (amnion, chorion, decidua, and villi) as well as in a wide spectrum of other tissues and cell lines. The distribution of the exon 3 retaining (hGHR) and exon 3 excluding (hGHRd3) isoforms of the hGHR mRNA shows a distinct tissue specificity. hGHR predominates in the liver, chorion, and decidua, while hGHRd3 predominated in the amnion, villi, and certain cell lines. The location of the exon 3 deletion and the prevalence of hGHRd3 in the villi suggest a parallel alteration in receptor function. We show that hGHRd3 mRNA encodes a stable and functional receptor. hGHRd3 mRNA is efficiently translated and processed in a rabbit reticulocyte lysate system as well as in an in vivo Xenopus laevis oocyte system. In Xenopus oocytes hGHRd3 is stably integrated into the cell membrane and binds and internalizes ligand as efficiently as hGHR. hGHRd3 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 kD and 20 kD isoform of the pituitary hGH-N. The results of these studies strongly support the expression of a functional hGHRd3 isoreceptor in the placenta which may serve in autocrine, paracrine, and/or endocrine function by the placentally expressed members of the hGH/Prl gene family.
Urbanek, Margrit, "Cloning and characterization of a placentally expressed isoform of the human growth hormone receptor" (1993). Dissertations available from ProQuest. AAI9331853.