GROWTH-HORMONE DOWN-REGULATES GROWTH-HORMONE RECEPTOR MESSENGER-RNA IN CHICKENS BUT DEVELOPMENTAL INCREASES IN GROWTH-HORMONE RECEPTOR MESSENGER-RNA 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 b y comparing the levels of cGHR mRNA in livers of normal chickens with that of GHR-deficient dwarf chickens. Since the sex-linked dwarf chick en lacks a functional cGHR, there are no genes activated as a result o f GH action. Examination of the early developmental profile of hepatic cGHR mRNA in normal and dwarf chickens should yield information on th e relative contribution of developmental and hormonal factors to the r egulation 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 a nd 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 expr essed. However, the expression of the truncated cGHR transcript (0.8 k b) in dwarf chickens increases about 5-fold between 1 and 7 weeks of a ge which suggests that the cGHR gene is overexpressed when not down-re gulated by GH. Furthermore, a single promoter appears to control expre ssion of cGHR transcripts in liver since primer extension analysis rev ealed the same 5'-end in both full-length and 0.8 kb transcripts. Thes e observations suggest that even though developmental increases in cGH R gene expression occur independently of GH action, GH, either directl y or indirectly, down-regulates expression of the cGHR gene in normal chickens. (C) 1997 Elsevier Science Ireland Ltd.