Human growth hormone increases apo(a) expression in transgenic mice

Ruixian Tao, Francesco Acquati, Santica M. Marcovina, Helen H. Hobbs

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Levels of Lp(a), an atherogenic lipoprotein that circulates in human plasma, are increased by the administration of growth hormone (GH). Many of the physiological effects of GH are mediated through insulin-like growth factor-1 (IGF-1), but ironically, IGF-1 treatment of humans is associated with a fall in plasma Lp(a) levels. To glean insight into the mechanism responsible for the GH-associated increase in plasma levels of Lp(a), we administered recombinant human GH (rhGH) to mice expressing a 370-kb human genomic fragment containing the apo(a) gene, 40 kb of 5'-, and 200 kb of 3'- flanking sequence [YAC-apo(a) transgenic mice]. The plasma levels of apo(a) and hepatic levels of apo(a) mRNA rose dramatically in the post-pubertal male mice in response to rhGH treatment. To determine whether the increase in plasma apo(a) was mediated by IGF-1, we treated castrated and noncastrated YAC-apo(a) transgenic mice with a continuous infusion of IGF-1 (100 μg/d) for 2 weeks, and plasma levels of apo(a) fell by ≃50%. Thus the effects of rhGH and IGF-1 administration on plasma levels of apo(a) in the YAC-apo(a) transgenic mice simulate those seen in humans. The coordinate changes in apo(a) mRNA and plasma levels of apo(a) in response to rhGH and IGF-1 strongly suggest that these 2 hormones have independent effects on the transcription of the apo(a) gene.

Original languageEnglish (US)
Pages (from-to)2439-2447
Number of pages9
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume19
Issue number10
StatePublished - Oct 1999

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Human Growth Hormone
Transgenic Mice
Somatomedins
Growth Hormone
3' Flanking Region
Messenger RNA
Genes
Lipoproteins
Hormones
Liver

Keywords

  • Apo(a)
  • Growth hormone
  • Insulin-like growth factor-1

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Human growth hormone increases apo(a) expression in transgenic mice. / Tao, Ruixian; Acquati, Francesco; Marcovina, Santica M.; Hobbs, Helen H.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 19, No. 10, 10.1999, p. 2439-2447.

Research output: Contribution to journalArticle

Tao, Ruixian ; Acquati, Francesco ; Marcovina, Santica M. ; Hobbs, Helen H. / Human growth hormone increases apo(a) expression in transgenic mice. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 1999 ; Vol. 19, No. 10. pp. 2439-2447.
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