Growth hormone activates hepatic and cerebral cholesterol metabolism in small-for-gestational age children without catch-up growth

Abstract

Background: Growth hormone (GH) replacement therapy improves hypercholesterolemia in patients with GH deficiency, suggesting that GH modulates cholesterol metabolism.

Objectives: We examined GH effects on lipid profiles and cholesterol-related markers reflecting hepatic and cerebral cholesterol metabolism in small-for-gestational age (SGA) children without catch-up growth.

Methods: This study examined SGA children without catch-up growth (n = 22) and healthy children (controls, n = 11). Based on parents' choice, 11 SGA children received GH at 0.23 to 0.25 mg/kg/d for 6 months, and at 0.34 to 0.36 mg/kg/d for the subsequent 6 months (GH (+) group). The other SGA children received no GH (GH (-) group, n = 11). We ascertained baseline and posttreatment lipid profiles and cholesterol-related markers reflecting hepatic and cerebral cholesterol metabolism.

Results: Baseline lipid profiles of SGA children and controls were similar. Serum 24S-hydroxycholesterol (marker for cerebral cholesterol metabolism) concentration was 19% lower in SGA children than in controls (P < .05). Compared with baseline, the GH (+) group low-density lipoprotein-cholesterol concentration had decreased by 6.6% during 6 months and 8.8% during 12 months (P < .01), whereas the high-density lipoprotein-cholesterol concentration had increased by 1.7% (P = .07) and 3.3% (P < .01). Serum 7α-hydroxycholesterol (marker for hepatic cholesterol elimination) concentration had increased by 34% at 6 months and 35% at 12 months (P < .01). In addition, 24S-hydroxycholesterol increased by 25% and 26% (P < .001). No marker for cholesterol synthesis or absorption changed. The GH (-) group lipid profiles and oxysterols remained unchanged during the observation period.

Conclusion: GH activates hepatic and cerebral cholesterol metabolism in SGA children without catch-up growth.

Keywords: 24S-hydroxycholesterol; 7α-hydroxycholesterol; Insulin-like growth factor I; Oxysterols.