INSULIN-LIKE GROWTH-FACTOR-I STIMULATES MYOFIBRILLAR GENES AND MODULATES ATRIAL-NATRIURETIC-FACTOR MESSENGER-RNA IN RAT-HEART

We have investigated the effect of a 6-day infusion of recombinant hum an (rh) IGF-I (0.3-1.0 mg/day) or rhGH (200 mU/day) into normal and hy pophysectomized rats on the ventricular expression of myofibrillar gen es (alpha- and beta-myosin heavy chain (MHC), skeletal and cardiac alp ha-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-fol d) by IGF-I (not statistically significantly with GH). Skeletal alpha- actin expression remained unchanged during IGF-I or GH treatment of no rmal rats, but was enhanced by both IGF-I and GH (2.5- and 2.8-fold re spectively) in hypophysectomized rats. Expression of cardiac alpha-act in in normal and hypophysectomized rats was not altered by either trea tment. 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 (possib ly 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 caus ed a shift from the beta- to the alpha-MHC isoform in hypophysectomize d rats.