Surgery, and

Growth hormone (GH) has an important role in the regula-tion of hepatic LDL receptor expression and plasma lipo-protein levels. This investigation was undertaken to evalu-ate if these effects of GH on hepatic LDL receptors are direct or mediated by insulin-like growth factor I (IGF-I). Two models were studied in which substitution with GH is important for the regulation of hepatic LDL receptors: hy-pophysectomized rats receiving high-dose ethynylestradiol or challenge with dietary cholesterol. The hypophysecto-mized rats were hormonally substituted by infusion with dexamethasone and L-thyroxine, and either GH or IGF-I. In both models, GH was essential for maintaining normal ex-pression of LDL receptors. In contrast, despite fully normal-ized plasma levels, IGF-I did not support the expression of hepatic LDL receptors. Analysis of plasma lipoproteins re-vealed that substitution with GH, but not with IGF-I, re-duced LDL and intermediate density lipoproteins. In addi-tion, determination of hepatic mRNA levels for apo B-100 and apo B-48 indicated that GH may be more effective than IGF-I in the promotion of apo B mRNA editing. In conclu-sion, GH has specific effects on hepatic LDL receptor ex-pression and plasma lipoprotein levels that are not medi-ated by IGF-I.