GH replacement reduces increased lipid peroxidation in GH-deficient adults.
BACKGROUND
GH replacement improves numerous metabolic abnormalities in GH-deficient patients; increased lipid peroxidation (LPO) has been observed in GH-deficient patients; however, it is unknown if LPO is influenced by GH replacement.


OBJECTIVE
To evaluate the extent to which GH replacement might reverse the increased LPO in GH-deficient adults and to analyse if this phenomenon might be involved in the improvement of metabolic disturbances due to GH treatment. Serum concentrations of malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA), as an index of LPO, were measured at baseline, and after 12 and 24 months of GH replacement in 40 adult patients with severe GH deficiency (both in adult- and childhood-onset) and in 40 healthy volunteers, matched for sex, age and body mass index (BMI). Correlations were evaluated between LPO and lipids, IGF-I, metalloproteinase-2 and -9 (MMP-2, -9), vascular endothelial growth factor (VEGF), BMI and GH dose.


RESULTS
LPO values in GH-deficient patients were several-fold higher than in controls [55.36 +/- 2.27 vs. 4.19 +/- 0.42 nmol/mg protein (mean +/- SEM), P < 0.0001] and decreased significantly over time with GH replacement to 38.61 +/- 2.15 nmol/mg protein (i.e. by approximately 30%), though still remaining markedly elevated compared with controls (P < 0.0001). The proatherogenic lipid profile parameters correlated positively with LPO in the childhood-onset subgroup before GH replacement. GH replacement restored the positive correlation between LPO and age in male patients (r = 0.57, P = 0.013; r = 0.8, P < 0.001, at 12 and 24 months of GH replacement, respectively).


CONCLUSIONS
GH replacement partially reverses the grossly abnormal LPO in GH-deficient adults. It is highly probable, therefore, that oxidative mechanisms are involved in the overall improvement of metabolic changes due to GH replacement.
Karbownik-Lewinska
Malgorzata
M
Department of Oncological Endocrinology, Medical University, Lodz, Poland.
Kokoszko
Agnieszka
A
Lewandowski
Krzysztof C
KC
Shalet
Stephen M
SM
Lewinski
Andrzej
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D004334:Drug Administration Schedule; D005260:Female; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000172:deficiency / Q000627:therapeutic use*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
D019382:Human Growth Hormone