Growth hormone induces low-density lipoprotein clearance but not bile acid synthesis in humans.

OBJECTIVE: Growth hormone (GH) induces hepatic low-density lipoprotein (LDL) receptors and lowers plasma cholesterol. We characterized the influence of GH treatment on plasma LDL clearance in normal humans and investigated the relative role of LDL receptor (LDLR) activity and stimulation of bile acid synthesis in subjects with different LDLR expression. METHODS AND RESULTS: Plasma clearance of autologous 125I-LDL was measured before and during 3 weeks of treatment with GH (0.1 IU/kg per day) in 9 healthy young males. Plasma LDL cholesterol was reduced by 13% and the fractional catabolic rate of LDL increased by 27%. More marked changes were seen in a patient with hypopituitarism substituted with GH (0.07 IU/kg per day) for 3 months. In a second study, GH dose-dependently reduced LDL cholesterol and increased Lp(a) levels in 3 groups of males: younger and elderly healthy subjects and heterozygous familial hypercholesterolemia (FH). No effect on bile acid synthesis measured by the plasma marker 7alpha-hydroxy-4-cholesten-3-one was observed. In an LDLR-deficient FH homozygote, LDL cholesterol was not affected by GH. CONCLUSIONS: GH treatment reduces plasma LDL cholesterol by inducing LDL clearance. In humans, LDLR expression is a prerequisite for this effect, whereas it is not related to stimulation of bile acid synthesis.

The magnitude of metabolically induced changes in the density of human low-density lipoproteins.

Radiolabelled low-density lipoproteins (LDL), obtained from a patient with heterozygous, familial hypercholesterolaemia and from a normal subject, were injected into the patient and two normal subjects. Two approaches were made to evaluate the kinetics of metabolism of these LDL: (1) by serial measurements of radioactivity in serum, urine and the whole body; (2) by observing the density of the labelled LDL from serum using density-gradient ultracentrifugation. No significant change was seen in the model density of the LDL in either the patient or the normal subjects, but there were changes in the skewness of the radioactivity peaks. This contrasts with previously published findings in the guinea pig, in which LDL radioactivity gradually accumulated in the densest particles. The guinea pig findings suggested that lipoproteins in the LDL region are structurally modified during their intravascular circulation. The present study indicates that modification leading to changes in density does not occur to any significant degree in the human, whose LDL represent the end product of intravascular metabolism of apolipoprotein B-containing lipoproteins.