Mode of growth hormone administration influences triacylglycerol synthesis and assembly of apolipoprotein B-containing lipoproteins in cultured rat hepatocytes

Abstract

Hypophysectomized female rats were treated for 1 week with thyroxine (10 micrograms/kg.day), cortisol (400 micrograms/kg.day), and bovine GH (1 mg/kg.day) either as two daily subcutaneous injections (GH x 2) or as a continuous subcutaneous infusion (GHc) in order to mimic the male and female specific GH secretory patterns, respectively. Hepatocytes were then isolated and kept in short-term cultures. Hypophysectomy decreased the synthesis of triacylglycerol. Treatment with GH x 2 had no or small effects, while GHc normalized the effect of hypophysectomy. ApoB-100 VLDL was assembled before apoB-48 VLDL. ApoB-48 was first assembled as an HDL particle (apoB-48 "HDL"). Hypophysectomy decreased the proportion of intracellular apoB-48 that was recovered as VLDL. Moreover, the proportion of apoB-48 of total apoB in VLDL decreased. Only GHc fully restored the effect of hypophysectomy by inducing an 4-fold increase in the assembly of apoB-48 VLDL, while treatment with GH x 2 gave rise to a 1.8-fold increase. Hypophysectomy resulted in a decrease in the proportion of apoB-48 that was secreted as VLDL and a decrease in the proportion of apoB-48 of total apoB in VLDL. Only treatment with GHc fully restored the secretion of apoB-48 VLDL by inducing an almost 4-fold increase in the secretion of apoB-48 VLDL, while the corresponding value for treatment with GH x 2 was 1.7. However, GH x 2 increased the proportion of the secreted apoB-48 that was recovered in VLDL to the levels found in normal rats and in rats treated with GHc, but this finding was due to a failure of GH x 2 treatment to increase the secretion of apoB-48 "HDL". In summary, a continuous infusion of GH to hypophysectomized rats, mimicking the female secretion of GH, normalized the triacylglycerol synthesis and secretion as well as apoB-48 VLDL assembly and secretion to those levels observed in hepatocyte cultures from intact female rats.