GROWTH-HORMONE RECEPTOR REGULATION IN GROWTH HORMONE-DEFICIENT DWARF RATS

In the rat, many actions of GH depend upon the sexually dimorphic patt ern of exposure to GH. Hepatic human GH (hGH) receptor binding differs between the sexes and is sensitive to GH deficiency, but this has mos tly been studied in acutely hypophysectomized rats, which lack all pit uitary hormones. We have used a strain of GH-deficient dwarf (Dw) rats to determine whether chronic GH deficiency alters the normal developm ental pattern and sexually dimorphic expression of hepatic GH receptor s. Adult female Dw rats had lower levels of I-125-labelled hGH binding (reflecting predominantly lactogenic receptors) than their normal cou nterparts whereas there was no difference between adult Dw and normal males; binding capacity increased from 25 days of age, becoming sexual ly dimorphic from 40 days to adulthood in both strains (% specific bin ding/mg protein: normal males 1.6 +/- 0.3, normal females 13.2 +/- 1.1 , Dw males 2.1 +/- 0.4, Dw females 10.0 +/- 0.6). In contrast, hepatic I-125-labelled bovine GH (bGH) binding (somatogenic receptors) was mu ch lower, and similar in both Dw and normal animals. A sex difference in I-125-labelled bGH binding was only seen in adult animals, and was considerably less marked in Dw rats compared with normal animals (norm al males 1.3 +/- 0.1, normal females 2.5 +/- 0.2, Dw males 1.9 +/- 0.2 , Dw females 2.4 +/- 0.2%/mg protein). Continuous hGH infusion stimula ted growth in female Dw rats, and raised somatogenic and lactogenic GH binding (3.2 +/- 0-4 and 19.6 +/- 2.5%/mg protein) compared with sham -infused controls (2.4 +/- 0.2 and 7.9 +/- 0.6%/mg protein). Dw rats h ad significantly smaller amounts of hepatic GH receptor mRNA than norm al rats, but there was no significant sex difference in GH receptor mR NA levels in the dwarfs. The pituitary GH deficiency in Dw rats was pr esent at birth and the relative deficit remained constant despite larg e increases in pituitary GH that occurred from birth to maturity. Thus whilst hepatic GH receptor expression can be altered by GH in Dw rats , their chronic GH deficiency causing severe dwarfism is accompanied b y only small differences in hepatic GH receptor expression.