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 (a-and b-myosin heavy chain (MHC), skeletal and cardiac a-actin) and of atrial natriuretic factor (ANF). In normal rats, b-MHC was not detectable either before or after IGF-I or GH, but a-MHC mRNA increased significantly (twofold) with GH (not statistically significant for IGF-I). In contrast to normal rats, hypophysectomized rats did not express a-MHC either before or after IGF-I or GH, but b-MHC was strongly expressed and significantly stimulated (1.8-fold) by IGF-I (not statistically significantly with GH). Skeletal a-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 a-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 b-to the a-MHC isoform in hypophysectomized rats.

Factors controlling cardiac myosin-isoform shift during hypertrophy and heart failure

“…Chronic IGF-1 and GH infusion has also been shown to induce αMHC mRNA in normal control rats, without changing the levels of βMHC transcripts. However, theses effects of growth factors were not observed in hypophysectomized rats, indicating that IGF-1 and GH stimulate the synthesis of αMHC transcripts indirectly, depending upon the hormonal status of the animal [103]. In a recent study, Kinugawa et al reported the induction of TRβ1 expression associated with running exercise-mediated physiologic hypertrophy [58].…”

Clinical evidence of growth hormone for patients undergoing abdominal surgery: Meta-analysis of randomized controlled trials

“…Underlying mechanisms of GH-induced fluid retention are as follows. GH could increase glomerular filtration rate mediated by insulin-like growth factor (IGF-I) [50][51][52] , stimulate the renin-angiotensin-aldosterone system (RAAS) [53][54][55][56][57] , reduce atrial natriuretic factors [58][59][60][61] , and prostaglandins could play a role in GH-induced fluid retention [62] . In the study of Berman et al…”

Effects of IGF-I on cardiac growth and expression of mRNAs coding for cardiac proteins after induction of heart hypertrophy in the rat

“…In vitro, it stimulates b-myosin heavy chain (MHC) and skeletal a-actin of cultured neonatal cardiac cells (1,2), and it enhances myofibril development and decreases smooth muscle a-actin and atrial natriuretic factor (ANF) in long-term cultures of adult rat cardiomyocytes (3,4). In vivo, IGF-I increases heart weight in normal and hypophysectomized rats (5)(6)(7)(8). In particular, IGF-I stimulates a-and b-MHC and skeletal a-actin, major components of myofibrils, and decreases ANF expression (6).…”

“…In vivo, IGF-I increases heart weight in normal and hypophysectomized rats (5)(6)(7)(8). In particular, IGF-I stimulates a-and b-MHC and skeletal a-actin, major components of myofibrils, and decreases ANF expression (6). Administration of IGF-I has been reported to improve doxorubicin-induced cardiomyopathy (9) and to enhance left ventricular function in normal rats (8) and in rats developing cardiac failure (7,10).…”

“…Since IGF-I enhances myofibril development (3,6), infusion of exogenous IGF-I might contribute to more rapid and more extensive myofibril building and thus enhance readaptation of the heart to overload.…”