The GH receptor (GHR) in regenerating rat liver following partial hepatectomy has been characterized in terms of mRNA levels, size of receptor variants, ligand binding, endocytosis and degradation. The GHR mRNA level, quantitated by solution hybridization, was found to be unchanged during the first 3 days of regeneration. The specific binding of 125I-labelled bovine GH to a GHR-enriched low density membrane fraction was, in contrast to the mRNA level, reduced to 10–35% between 12 and 24 h after partial hepatectomy, and remained low until 48 h. Removal of endogenous GH by MgCl2 treatment did not further increase the binding of 125I-labelled bovine GH. Affinity cross-linking experiments revealed reduced labelling of a specific receptor binder at 95 kDa, assuming a 1:1 stoichiometric binding of the ligand, in regenerating liver. Additional evidence for a decrease in the amount of functional GHR was provided by the finding of decreased levels of IGF-I mRNA in the liver remnant, with a nadir at 50% between 24 and 48 h after hepatectomy. GH binding was reduced to a similar extent in hypophysectomized animals subjected to partial hepatectomy, implying that pituitary GH is not involved in the mechanism of GHR down-regulation.
The in-vivo uptake of 125I-labelled bovine GH, which is correlated with the number of GHRs available for binding in the plasma membrane, was decreased to 23% in an endosome-enriched membrane fraction from regenerating liver at 24 h. No qualitative differences in the size distribution of endocytosed receptor-ligand complexes in normal and regenerating liver were noted. The degradation of internalized 125I-labelled bovine GH, analysed as trichloroacetic acid solubility, was unaffected during regeneration.
It is concluded that the reduced number of GHRs available for binding in regenerating liver cells is caused by an alteration exerted at a post-translational level during receptor biosynthesis.
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