Increased Growth Hormone Binding to Liver Membranes of Obese Zucker Rats

Abstract

Developmental changes in hepatic growth hormone binding sites were examined in the genetically obese male fa/fa rats and in the lean littermates. At 16 days, fa/fa pups are normoinsulinemic; the specific binding of 125I-hGH to liver membranes is comparable in the two genotypes. At 4 weeks and later on, plasma membranes and Golgi fractions of male obese Zucker rats have more GH binding sites than lean littermates. The GH pituitary content is comparable in the two genotypes from 2 to 8 weeks and in 14-week-old fa/fa rats it is half that in lean animals. In the two genotypes plasma IGFI dramatically increases during puberty. At 4 weeks, plasma IGFI level is significantly higher in fa/fa rats than in lean littermates. In this model of genetic obesity, an increased GH binding to liver membranes is observed after the third week of life, shortly after the onset of hyperinsulinemia in the fa/fa rat.

Nutritional Status and Growth Hormone-Binding Protein

“…In rats with protein calorie restriction, post-receptor defects are also involved in the GH-resistant state: in young rats fed a 5% protein diet, infusion of rat GH did not restore IGF-1 to control values despite normalization of hepatic GH-binding sites [27]. An upregulation of the number of GH receptors in hepatocyte and adipocyte has also been shown in genetically obese male Zucker rats [28,29], Nutrition is an important regulator of plasma GHbinding activity and a strong correlation was observed in this study between BMI and GHBP levels. BMI was pre viously found to be correlated w ith GHBP even within the range of normal body weight [30][31][32], The exact nutri tional factors responsible for the GHBP/GH receptor reg ulation in different nutritional situations are unknown, but insulin probably plays a role: (1) in obese Zucker rats, the increase in the concentration of tissue GH receptors was observed shortly after the onset of hyperinsulinemia [28], and (2) GHBP is low in insulin-dependent diabetes mellitus [33],…”