Insulin-like growth factor-I stimulates myofibrillar genes and modulates atrial natriuretic factor mRNA in rat heart.

Abstract

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.