Distribution and abundance of messenger ribonucleic acid for growth hormone receptor isoforms in human tissues

Two alternatively spliced exon 9 variants of human GH receptor (GHR) messen ger ribonucleic acid (mRNA), GHR-(1-279) and GHR-(1-277), were recently ide ntified in liver. They encode receptor proteins lacking most of the intrace llular domain and inhibit GH action in a dominant negative manner. Little i s known about tissue distribution and abundance of these GHR isoforms. We h ave developed quantitative RT-PCR assays specific for the full-length and t runcated GHRs and investigated their expression in various human tissues an d cell lines. The mRNA of full-length GHR and GHR-(1-279) were readily detectable in all tissues investigated, with liver, fat, muscle, and kidney showing high leve ls of expression. These two receptor isoforms were also detected in a range of human cell lines, with strongest expression in IM9, a lymphoblastoid ce ll line. In contrast, GHR-(1-277) message was expressed at low levels in li ver, fat, muscle, kidney, and prostate and in trace amount in IM9 cells. Full-length GHR was the most abundant isoform, accounting for over 90% of t otal receptor transcripts in liver, fat, and muscle for quantitative RT-PCR . However, liver had 2- to 4-fold more full-length receptor mRNA and 16- to 40-fold more GHR-(1-277) mRNA than fat and muscle, whereas the mRNA levels of GHR-(1-279) were similar in the three tissues. GHR-(1-279) constituted less than 4% in liver and 7-10% in fat and muscle. GHR-(1-277) accounted fo r 0.5% of total GHR transcripts in liver and less than 0.1% in the other tw o tissues. These data suggest that the absolute and relative abundance of m RNA of the three GHR isoforms may be tissue specific. The regulation of exp ression of exon 9 alternatively spliced GHR variants may provide a potentia l mechanism for modulation of GH sensitivity at the tissue level.