REDUCED EXPRESSION OF THE HEPATIC GROWTH HORMONE (GH) RECEPTOR IN EXPERIMENTAL UREMIA

Abstract

In uremia reduced longitudinal growth and decreased hepatic IGF-I secretion despite elevated GH serum levels point to a resistance to the action of GH, which could be a consequence of a reduced hepatic GH receptor (R) expression. To addressthis hypothesis we studied the hepatic GH-R mRNA content in uremic female SD rats (n=7 per group) subjected to 5/6 nephrectomy (U) compared to sham operated pairfed (PC) or ad libitum fed (aLC) controls. Animals were treated with 10 IU rhGH/kg/day, or solvent for 10 days. Total RNA was prepared from rapidly frozen liver tissue and the GH-R mRNA quantified by solution hybridization. Mean (±SD) weight gain was lower in U (21.4±7.9 g) compared to PC (24.1±5.9; P<0.005) and aLC (33.5±6.3; P<0.005). Hepatic GH-R mRNA was reduced in U (0.79±0.39 amol/ug DNA) vs PC (1.46±0.32; P<0.005) and vs aLC (2.66±0.73, P<0.001). Exogenous rhGH slightly increased (n.s.) GH-R mRNA in all groups. Plasma GH binding protein (BP) levels (RIA) in U were 11.1±4.4 ng/ml, in PC 8.2±2.3, in aLC 5.7±2.5 (P<0.01). We conclude that experimental uremia is accompanied by a marked reduction of hepatic GH-R expression. The data in the pairfed animals indicate that this effect is only partially attributable to malnutrition. Increased plasma GHBP levels in U might be interpreted as a consequence of reduced renal clearance.