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Human growth hormone increases apo(a) expression in transgenic mice
R Tao1, F Acquati, S M Marcovina
1Departments of Internal Medicine and Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235-9046, USA.
Arteriosclerosis, Thrombosis, and Vascular Biology
|October 16, 1999
Summary
Growth hormone (GH) increases plasma lipoprotein(a) [Lp(a)] levels, while insulin-like growth factor-1 (IGF-1) decreases them. This study in YAC-apo(a) transgenic mice reveals independent hormonal effects on apo(a) gene transcription.
Area of Science:
- Biochemistry
- Endocrinology
- Genetics
Background:
- Lipoprotein(a) [Lp(a)] is an atherogenic lipoprotein. Growth hormone (GH) administration increases plasma Lp(a) levels in humans.
- Insulin-like growth factor-1 (IGF-1), a mediator of GH effects, paradoxically decreases plasma Lp(a) levels in humans.
Purpose of the Study:
- To investigate the mechanism underlying GH-induced increases in plasma Lp(a) levels.
- To elucidate the independent roles of GH and IGF-1 in regulating Lp(a) production.
Main Methods:
- Administration of recombinant human GH (rhGH) to YAC-apo(a) transgenic mice carrying a human apo(a) gene fragment.
- Treatment of castrated and noncastrated YAC-apo(a) transgenic mice with continuous IGF-1 infusion.
- Measurement of plasma apo(a) and hepatic apo(a) mRNA levels.
Main Results:
- rhGH administration significantly increased plasma apo(a) and hepatic apo(a) mRNA levels in male mice.
- IGF-1 treatment led to a ~50% reduction in plasma apo(a) levels.
- The observed hormonal effects in mice mirrored those seen in humans.
Conclusions:
- GH and IGF-1 exert independent effects on the transcription of the apo(a) gene.
- These findings provide insights into the complex regulation of Lp(a) metabolism by GH and IGF-1.