Regulation of growth hormone receptor gene expression.

Pituitary growth hormone (GH) is essential for postnatal growth in animals. GH exerts its actions by direct effect on target organs and by stimulating the production of insulin-like growth factor I (IGF-I). At the tissue level, the pleiotropic actions of GH result from the interaction of GH with a specific cell surface receptor, the GH receptor (GHR). The GHR belongs to the hematopoietic receptor superfamily. The human GHR is the product of a single gene located on chromosome 5p13.1-p12 and spans at least 87 kb. Transcripts from this gene are characterized by the presence of disparate 5' untranslated exons. In the liver at least eight different GHR 5' untranslated regions (UTRs) have been described. This heterogeneity in the 5' UTR most likely results from the splicing of the various exon 1 fragments to a common splice site located 11 bp upstream of the initiating ATG. Heterogeneity in the 5' UTR sequences of the GHR transcripts indicates that transcriptional control of the locus is complex. GHR gene expression is minimal to absent in the fetus, with the postnatal increase in expression in the liver being maximal during pregnancy. GHR gene expression is also regulated by factors such as nutritional intake, GH, steroid hormones, and diabetes mellitus. Available information about the molecular mechanisms regulating expression of the GHR gene is discussed. Thus the GHR gene presents a picture of multiple 5' untranslated exons under the control of multiple promoters. The use of alternate promoters for initiation of transcription in conjunction with differential splicing allows for exquisite regulation of gene expression. This schema is appropriate for a protein that is essential to many of the physiological processes that are crucial for the survival and well-being of the organism.