Low plasma lecithin : cholesterol acyltransferase and lipid transfer protein activities in growth hormone deficient and acromegalic men: role in altered high density lipoproteins

Growth hormone (GH) deficiency and acromegaly may be associated with increa sed cardiovascular risk. Little is known about alterations in high density lipoproteins (HDL) in these conditions. Lecithin:cholesterol acyl transfera se (LCAT) has the ability to esterify free cholesterol (FC) in HDL. Cholest eryl ester transfer protein (CETP) is able to transfer cholesteryl esters ( CE) from HDL to very low and low density lipoproteins (VLDL and LDL). Durin g phospholipid transfer protein (PLTP) -mediated HDL remodelling, small pre P-HDL particles are generated which serve as accepters for cellular choles terol and provide the initial LCAT-substrate. We documented plasma lipids, LCAT, CETP and PLTP activity levels as well as plasma cholesterol esterific ation (EST) and cholesteryl ester transfer (CET) in 12 adult men with acqui red GH deficiency, 12 acromegalic men and 24 healthy male subjects. All GH deficient and acromegalic patients received conventional hormonal replaceme nt therapy if necessary. VLDL + LDL cholesterol and plasma triglycerides we re higher in GH deficient (P < 0.01 and P < 0.05) and acromegalic patients (P < 0.05 and P < 0.01) than in healthy subjects. HDL cholesterol and HDL C E were lower (P < 0.05 for both) and the HDL FC/CE ratio was higher (P < 0. 01) in these patient groups compared to healthy subjects. Plasma LCAT, CETP and PLTP activity levels were lower in acromegalic patients (P < 0.01 for all) and CETP activity was lower in GH deficient patients (P < 0.01) compar ed to healthy subjects. Plasma EST and CET were decreased in both acromegal ic (P < 0.01 for both) and GH deficient patients (P < 0.05 for both). Multi ple regression analysis demonstrated independent negative relationships of plasma insulin-like growth factor I with plasma LCAT (P = 0.0001), CETP (P = 0.009) and PLTP activity levels (P = 0.021). Plasma LCAT (P = 0.0001) and CETP activity (P = 0.0001) were also negatively associated with (substitut ion therapy for) adrenal insufficiency. In conclusion, GH deficient and acr omegalic patients show abnormalities in HDL, consistent with impaired LCAT action. Decreases in plasma EST and CET in such patients, as well as a low PLTP activity in acromegaly suggest that reverse cholesterol transport may be impaired, contributing to increased cardiovascular risk. (C) 2000 Elsevi er Science Ireland Ltd. All rights reserved.