Growth hormone down-regulates growth hormone receptor mRNA in chickens but developmental increases in growth hormone receptor mRNA occur independently of growth hormone action.

The purpose of this study was to determine the role of growth hormone (GH) in regulating expression of the chicken GH receptor (cGHR) gene by comparing the levels of cGHR mRNA in livers of normal chickens with that of GHR-deficient dwarf chickens. Since the sex-linked dwarf chicken lacks a functional cGHR, there are no genes activated as a result of GH action. Examination of the early developmental profile of hepatic cGHR mRNA in normal and dwarf chickens should yield information on the relative contribution of developmental and hormonal factors to the regulation of cGHR gene expression. Using a sensitive RNase protection assay, we found that the abundance of the major cGHR transcripts (4.3, 3.2 and 0.8 kb) in normal chickens increases about 2-fold between 1 and 7 weeks of age. Due to a splice site mutation in the dwarf chicken, the two larger transcripts encoding the full-length cGHR are not expressed. However, the expression of the truncated cGHR transcript (0.8 kb) in dwarf chickens increases about 5-fold between 1 and 7 weeks of age which suggests that the cGHR gene is overexpressed when not down-regulated by GH. Furthermore, a single promoter, appears to control expression of cGHR transcripts in liver since primer extension analysis revealed the same 5'-end in both full-length and 0.8 kb transcripts. These observations suggest that even though developmental increases in cGHR gene expression occur independently of GH action, GH, either directly or indirectly, down-regulates expression of the cGHR gene in normal chickens.