Ghrelin in the heart and growth hormone: which is chicken, which is egg?

In their study published in this issue, Iglesias et al. give the vascular effects, independent of GH release, has been first evidence that ghrelin is synthesized and secreted by cardiomyocytes. Ghrelin is a 28-amino acid peptide containing an n-octanoyl modification at serine 3. It acts on the pituitary and hypothalamus to stimulate growth hormone (GH) release, food intake, and adiposity. It has been newly identified as the endogenous ligand of the orphan GH secretagogues (GHS) receptor, GHSR-1a, that is mostly expressed in pituitary and hypothalamus. Acylation of ghrelin is required for activation of GHSR-1a, whereas des-acyl ghrelin, which is far more abundant than ghrelin, does not bind GHSR-1a and is devoid of any endocrine activity [1,2]. GH and its mediator, insulin-like growth factor (IGF)-1, are anabolic hormones that are essential for myocardial development and performance. Receptors for both GH and IGF-1 are expressed by cardiac myocytes; therefore, GH may act directly on the heart or via the induction of local or systemic IGF-1, whereas IGF-1 may act by endocrine, paracrine, or autocrine mechanisms [3]. Studies on animal models of pressure and volume overload report up-regulation of cardiac IGF-1 production and expression of GH and IGF-1 receptors, implying that the local regulation of these factors is influenced by haemodynamic changes. Other studies further show that GH administration improves cardiac performance in experimental heart failure [3]. However, the overall clinical benefits of GH therapy for patients with chronic heart failure have been disappointing [4]. This led to propose GHS as an alternative approach for increasing systemic levels of GH in a more physiological profile than direct exogenous administration. The synthetic molecules GHS activate GHSR-1a and GH release in the pituitary and hypothalamus. GHS treatment provides beneficial effects on left ventricular structure and function in the experimental model of rapid pacing-induced heart failure in pig [5]. In this first study, benefits of GHS treatment are mostly imputed to a release of endogenous GH. However, the possibility that GHS have direct cardio-