Decreased expression of the growth hormone receptor and growth hormone binding protein in rat liver nodules

Abstract

The growth hormone receptor (GHR) and growth hormone-binding protein (GH-BP) expression were characterized in liver nodules and hepatomas from male Wistar rats. The mRNA levels of GHR and GH-BP, studied by northern blot analysis and solution hybridization, were 35-50% (in nodules) and 2-6% (in hepatomas) of the level found in liver from untreated, age-matched rats. The binding of 125I-labeled human growth hormone to a low-density membrane fraction (LDMF) containing Golgi and endosome membranes in the presence of excess ovine prolactin was 75-80% lower in nodules than in liver. When endogenous ligand was removed, the binding increased in nodules but not in liver. Affinity cross-linking experiments revealed identical specific receptor-binding protein complexes at Mr of 95,000, 55,000, and 43,000 in both nodules and liver, assuming stochiometric binding of ligand. The in vivo endocytosis of 125I-labeled bovine growth hormone correlated with the level of GH binding and was thus reduced 75-80% in nodules, compared with liver. The level of insulin-like growth factor-I (IGF-I) mRNA was reduced by 50% in nodules; however, GH administration resulted in a twofold induction of IGF-I mRNA in both nodules and liver. It is concluded that the greater proportion of occupied GHR in nodules could result from an impaired dissociation of endogenous GH, which might explain the reduced GHR mRNA expression. Furthermore the low GHR mRNA expression may reflect a de-differentiated phenotype in nodules.