Growth hormone increases and insulin-like growth factor-I decreases circulating lipoprotein(a)
BACKGROUND
Elevated serum lipoprotein(a) (Lp(a)) is a strong risk factor for coronary artery disease (CAD). Genetic factors appear to account for the major variance in Lp(a) levels but the contribution hormones make in modulating Lp(a) levels is not yet clear. In the present investigation we determined the effects of human growth hormone (hGH) and insulin-like growth factor-I (IGF-I) on circulating Lp(a).


METHODS
Four groups of patients were studied. Group a: adults with GH deficiency (n = 7) treated with hGH (0.05 U/kg/day, s.c.); group b: girls with Turner syndrome (n = 7) treated with hGH (0.1 U/kg/day, s.c.); group c: prepubertal boys with idiopathic short stature (n = 6) treated with the GH secretagogue (GHRP) hexarelin (60 micrograms t.i.d. intranasally); group d: Laron syndrome patients (n = 10) treated with IGF-I (100-200 micrograms/kg/day, s.c.). Following overnight fasting, serum was sampled before the initiation of treatment and during 6-9 months treatment.


RESULTS
Serum IGF-I rose significantly in all the subjects in all four groups. In the first three groups in which IGF-I was elevated by exogenous or endogenous GH stimulation, serum Lp(a) increased significantly (119 +/- 35%, P < 0.01; 126 +/- 44%, P < 0.05; 102 +/- 29%, P < 0.01 for groups a, b, and c respectively). By contrast, serum Lp(a) levels decreased in group d to whom exogenous IGF-I was administered (-66 +/- 5%, P < 0.001). The differential effect of endogenous vs exogenous IGF-I on serum Lp(a) paralleled the behaviour of serum insulin. Insulin was significantly increased in all the subjects receiving hGH or GHRP (65.2 +/- 31%, P = 0.109; 93.7 +/- 53%, P = 0.062; 353.8 +/- 52.7%, P < 0.01 for groups a, b, and c respectively) whereas insulin levels were reduced following exogenous administration of IGF-I (-34.1 +/- 9.1%, P < 0.01).


CONCLUSIONS
We conclude that long-term GH treatment increases and IGF-I decreases circulating levels of Lp(a). These findings may have clinical relevance in view of the increasing use of hGH in children and adults and the role of Lp(a) as a CAD risk factor.
Laron
Z
Z
Endocrinology and Diabetes Research Unit, Schneider Children's Medical Center, Israel.
Wang
X L
XL
Klinger
B
B
Silbergeld
A
A
Wilcken
D E
DE
D000328:Adult; D000375:Aging / Q000097:blood; D002648:Child; D003327:Coronary Disease / Q000453:epidemiology / Q000209:etiology / Q000503:physiopathology; D005260:Female; D006130:Growth Disorders / Q000188:drug therapy / Q000503:physiopathology; D013006:Growth Hormone / Q000494:pharmacology* / Q000627:therapeutic use; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D015994:Incidence; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000494:pharmacology* / Q000627:therapeutic use; D017270:Lipoprotein(a) / Q000097:blood*; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D012307:Risk Factors
D006133:Growth Substances; D007328:Insulin; D017270:Lipoprotein(a); D009842:Oligopeptides; D011994:Recombinant Proteins; C086184:hexarelin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone