Growth Hormone Therapy in Heart Failure: Where Are We Now?

Catherine Demers, MD, MSc, Robert S. McKelvie, MD, PhD

Disclosures

CHF. 2003;9(2) 

In This Article

GH and the Heart

GH is a small peptide secreted by the somatotropic cells of the anterior pituitary gland[9,10] (Figure). GH receptors are present on a number of organs, and stimulation of the GH receptor results in skeletal muscle growth, regulation of lipolysis, and anti-insulin effects.[10] GH may affect the heart and vessels directly or indirectly through circulating IGF-I, and IGF-I may have a central role in the hypertrophic growth response.[9] Most of the IGF-I is synthesized by the liver and circulates in the blood, bound to proteins (IGFBP) (IGFBP-3 is the main binding protein) that increase the circulating half-life of IGF-I; GH and IGF-I receptors are expressed in cardiac tissue. In addition, cardiac myocytes may produce local IGF-I, with stimulation of tissue growth, through paracrine and autocrine mechanisms promoting cardiac hypertrophy and increased mRNA production in the myocardium, more so in areas of mechanical stress.[10] Conditions of pressure and volume overload associated with increased systolic wall stress trigger gene expression of the IGF-I/GH receptors, suggesting a potential role of the GH/IGF-I axis in HF.

Possible sites of action of growth hormone on the cardiovascular system

Administration of GH stimulates molecular changes in the heart, with increased expression and concentration of IGF-I acting as a mediator of cardiac growth.[11,12,13] Myocardial mass is increased with conversion of myocardial contractile protein to the more efficient, forceful phenotype, low adenosine triphosphatase V3 myosin isoform.[14,15] GH may promote growth through mechanisms other than IGF-I with induction of the c-myc proto-oncogene and via platelet-derived growth factor. Finally, calcium-dependent contractile reserve in blood vessels and myocardium may be influenced through direct effects of GH.[16] In the post-myocardial infarction (MI) hearts of rats treated with GH, levels of sarcoplasmic reticulum calcium adenosine triphosphatase 2 (SERCA2) mRNA and protein were increased, suggesting restoration of contractile reserve in this animal model.[16] In summary, GH may increase contractility, increase ventricular mass through anabolic effects on cardiac myocytes, with a reduction in left ventricular wall stress, and reduce systemic vascular resistance by potentially increasing nitric oxide production.[17]

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