Insulin-like growth factor-I stimulates myofibrillar genes and modulates atrial natriuretic factor mRNA in rat heart.
We have investigated the effect of a 6-day infusion of recombinant human (rh) IGF-I (0.3-1.0 mg/day) or rhGH (200 mU/day) into normal and hypophysectomized rats on the ventricular expression of myofibrillar genes (alpha- and beta-myosin heavy chain (MHC), skeletal and cardiac alpha-actin) and of atrial natriuretic factor (ANF). In normal rats, beta-MHC was not detectable either before or after IGF-I or GH, but alpha-MHC mRNA increased significantly (twofold) with GH (not statistically significant for IGF-I). In contrast to normal rats, hypophysectomized rats did not express alpha-MHC either before or after IGF-I or GH, but beta-MHC was strongly expressed and significantly stimulated (1.8-fold) by IGF-I (not statistically significantly with GH). Skeletal alpha-actin expression remained unchanged during IGF-I or GH treatment of normal rats, but was enhanced by both IGF-I and GH (2.5- and 2.8-fold respectively) in hypophysectomized rats. Expression of cardiac alpha-actin in normal and hypophysectomized rats was not altered by either treatment. IGF-I and GH decreased ventricular expression of ANF in normal rats by 63% and 45% respectively, but did not influence ANF expression in hypophysectomized rats. Our results show that IGF-I and GH (possibly via IGF-I) stimulate expression of myofibrillar genes and modulate ANF mRNA concentrations in rat heart ventricles in vivo, depending on the hormonal status of the animals. However, neither IGF-I nor GH caused a shift from the beta- to the alpha-MHC isoform in hypophysectomized rats.
Donath
M Y
MY
Department of Medicine, University Hospital, Zürich, Switzerland.
Gosteli-Peter
M A
MA
Hauri
C
C
Froesch
E R
ER
Zapf
J
J
D000199:Actins / Q000235:genetics; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics*; D015870:Gene Expression; D006352:Heart Ventricles / Q000378:metabolism; D019382:Human Growth Hormone / Q000494:pharmacology; D006801:Humans; D007016:Hypophysectomy; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009210:Myofibrils / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology
D000199:Actins; D012333:RNA, Messenger; D011994:Recombinant Proteins; C472610:atrial natriuretic peptide, rat; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D009320:Atrial Natriuretic Factor; D018995:Myosin Heavy Chains