The role of the GH/IGF-I axis for cardiac function and structure

There is ample evidence to support a role for the GH/ICF-I axis in regulati on of cardiac growth, structure and function. GH may act directly on the he art or through circulating IGF-I (Fig, 1). Moreover, GH has been found to r egulate local production of IGF-I in the heart. Both the GH-R and IGF-I-R a re expressed in cardiac tissue. Hence, the IGF-I-R receptor can theoretical ly be activated through locally produced IGF-I acting via autocrine/paracri ne mechanisms, or via circulating IGF-I exerting its effects as an endocrin e agent. During conditions of pressure and volume overload, an increased sy stolic wall stress triggers an induction of gene expression of IGF-I GH-R a nd possibly IGF-I-R implying a potential role for the GH/IGF-I axis in the development of adaptive hypertrophy of the heart and vessels. Cardiovascula r effects of GH in clinical studies include beneficial effects on contracti lity, exercise performance and TPR, and experimental studies suggest an inc reased Ca2+ responsiveness as one possible underlying cause, although effec ts of GH and IGF-I on apoptosis may possibly also play a role. The GH secre tagogue hexarelin improves cardiac function after experimental myocardial i nfarction either through an increased GH secretion or possibly through a ca rdiac GHS receptor, although this needs further investigation. Moreover, it is clear that further basic and clinical studies are required to gain insi ght into the GH and IGF-I mechanisms of action and to monitor long-term eff ects when GH is administered as substitution therapy or as an agent in the treatment of congestive heart failure.