Plasma cholesteryl ester transfer protein and lipoprotein levels during treatment of growth hormone-deficient adult humans.
ABSTRACT The incidence of atherosclerosis is increased in growth hormone (GH) deficient-individuals. Nonetheless, the antiatherogenic benefits of GH replacement therapy remain uncertain. In this study the effect of human recombinant growth hormone (hrGH) replacement therapy administered to GH-deficient adults on the plasma cholesteryl ester transfer protein (CETP) concentration and activity was analyzed. These findings were related to changes in the concentrations of the plasma lipoproteins. The hrGH was administered for 12 mon to human GH-deficient patients (n = 13; 8 men, 5 women). During the study plasma lipoproteins were separated by ultracentrifugation, and plasma cholesterol esterification rate (CER), endogenous CETP activity, and CETP concentration were measured. GH replacement therapy transiently (at 3 mon) lowered plasma concentration of CETP and low density lipoprotein-cholesterol (LDL-C) and raised total triglycerides. Furthermore, hrGH permanently increased both the plasma lipoprotein(a) [Lp(a)] concentration, which is known as atherogenic, and the proportion of cholesteryl ester in the high density lipoprotein2 (HDL2) particles, which is potentially atheroprotective. The simultaneous decrease of the plasma CETP and LDL-C concentrations elicited by hrGH indicated a close relationship between LDL metabolism and the regulation of the CETP gene expression. Endogenous CETP activity and the CER were not modified because these parameters are regulated in opposite ways by plasma levels of triglycerides; that is, CER increased and CETP decreased.
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ABSTRACT: The effects of growth hormone (GH) replacement on plasma lecithin:cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP), and phospholipid transfer protein (PLTP), factors involved in high density lipoprotein (HDL) metabolism, are unknown. We carried out a 6 months study in 24 GH-deficient adults who were randomized to placebo (n = 8), low dose GH (1 U daily, n = 8), and high dose GH (2 U daily, n = 8), followed by a 6 months open extension study with high dose GH (1 drop-out). No significant changes in plasma lipoproteins, LCAT, CETP, and PLTP activities, cholesterol esterification (EST) and cholesteryl ester transfer (CET) were observed after placebo. After 6 months of GH (combined data, n = 24), very low + low density lipoprotein (VLDL + LDL) cholesterol (P < 0.05) and apolipoprotein B (P < 0.05) decreased, whereas HDL cholesterol and HDL cholesteryl ester increased (P < 0. 05). Prolonged treatment showed comparable effects. Plasma apolipoprotein A-I and Lp[a] remained unchanged. Plasma LCAT (P < 0. 01) and CETP activities (P < 0.01), as well as EST (P < 0.01) and CET decreased (P < 0.01) after 12 months of GH (n = 15), but PLTP activity did not significantly change. Changes in EST and CET after 12 months of treatment were independently related to changes in plasma LCAT (P = 0.001 and CETP activity (P = 0.01). In conclusion, GH replacement therapy improves the lipoprotein profile in GH-deficient adults. Chronic GH replacement lowers plasma LCAT and CETP activities, contributing to a decrease in cholesterol esterification and cholesteryl ester transfer. These effects may have consequences for HDL metabolism and reverse cholesterol transport.The Journal of Lipid Research 06/2000; 41(6):925-32. · 4.39 Impact Factor
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ABSTRACT: Plasma cholesteryl ester transfer protein (CETP) concentrations were measured in Japanese subjects by an ELISA with two different monoclonal antibodies that were raised against rabbit CETP and cross-reacted against human CETP. Among 63 patients who consecutively underwent coronary angiography, the plasma CETP of 37 patients with luminal stenosis > or = 50% in their coronary arteries was not significantly different from that of the 26 patients with luminal stenosis < 50%. No other lipoprotein-related measurement except HDL-cholesterol differentiated the two groups. Among 40 hypercholesterolemic patients, no lipoprotein-related measurement other than LDL-cholesterol was found to positive correlate with the CETP. Before and after the treatment of 23 patients with simvastatin 5 mg a day for 4 weeks, plasma CETP markedly decreased in those whose pretreatment CETP was > or = 3 mg/L; no change was observed for those with lower pretreatment CETP. In the former group, negative correlation between CETP and HDL-cholesterol was demonstrated only in the posttreatment plasma.Clinical Chemistry 07/1998; 44(7):1466-73. · 7.15 Impact Factor
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ABSTRACT: We investigated the influence of gender and apoE and apo(a) phenotypes as well as the effect of the metabolic effects of growth hormone (GH) on the effect of GH therapy on serum lipoprotein concentrations in GH-deficient (GHD) adults. Forty-four consecutive patients, 30 men and 14 women aged 46.5 (range, 19 to 76) years with GHD due mainly to pituitary tumors, were treated with recombinant human GH for 12 months. Serum concentrations of lipoproteins, insulin, thyroxine, and insulin-like growth factor-I were determined, body composition was assessed by bioelectrical impedance, and apo(a) and apoE phenotypes were analyzed. Lipoprotein(a) [Lp(a)] concentrations in the GHD subjects were compared with a gender- and apo(a) phenotype-matched control group. After 12 months of GH treatment, the total cholesterol, LDL cholesterol, and apoB concentrations decreased, the HDL cholesterol and apoE concentrations increased, and the apoA-I and triglyceride concentrations were unchanged. Before treatment, the Lp(a) concentration was similar to that in the control group. However, after 12 months of treatment, the Lp(a) concentration had increased by 44% and 101% above baseline and the control group, respectively. Men and women responded differently to GH, with a more marked increase in Lp(a) concentration and fat-free mass and a more pronounced decrease in body-fat mass in men. Apo(a) phenotypes had no major influence on the effect of GH therapy. The only significant difference between apoE phenotypes was a higher baseline Lp(a) concentration among apoE4 heterozygotes.(ABSTRACT TRUNCATED AT 250 WORDS)Arteriosclerosis Thrombosis and Vascular Biology 01/1996; 15(12):2142-50. · 6.34 Impact Factor