EXPRESSION OF 2 ISOFORMS OF THE HUMAN GROWTH-HORMONE RECEPTOR IN NORMAL LIVER AND HEPATOCARCINOMA

In man, two isoforms of growth hormone receptor (GHR) have been reported. The first, hGHR corresponds to the original form described by Leung et al. (J. Biol. Chem. 264 (1987) 9905-9910). The second, hGHRd3, missing 22 N-terminal amino acids is encoded by an mRNA derived from alternative splicing and deletion of the third exon. This latter form has been isolated from placenta and its tissue distribution, as well its function warrant further examination. We studied the relative expression of the two isoforms of GHR in liver at various stages of development or differentiation. Several samples from fetal livers and hepatocarcinomas were analysed and we observed that hGHR and hGHRdS can be expressed solely or coordinately. Furthermore, we investigated the possibility that alternative splicing of exon 3 could be related to the specific use of different promoters. Our data show that both isoforms have identical 5'-untranslated regions in normal liver or in hepatoma cell lines. Finally, these experiments strongly suggest that hGHRd3 is efficiently translated as a functional receptor, with the soluble form of GHR being recovered in the cell media. The results of the present study support the concept that both isoforms are expressed in human liver, with exon 3 alternative splicing being neither tissue specific nor related to hepatic differentiation.