Translational Medicine in Fish-derived Peptides: From Fish Endocrinology to Human Physiology and Diseases

Abstract

Abstract. Recent studies have revealed the importance of fish-derived peptide hormones to human endocrinology. These peptides include melanin-concentrating hormone (MCH), urocortins (human urotensin-I), and urotensin-II. MCH, a hypothalamic peptide, is a potent stimulator on appetite. Urocortins, e.g. urocortin 1 and urocortin 3 (stresscopin), are endogenous ligands for the corticotropin-releasing factor (CRF) receptors, particularly CRF type 2 receptor, that mediates a vasodilator action, a positive inotropic action and a central appetite-inhibiting action. These actions mediated by CRF type 2 receptor may ameliorate the stress response. Human urotensin-II is a potent vasoconstrictor peptide, while it acts as a vasodilator on some arteries. Human urotensin-II is expressed in various types of cells and tissues, including cardiovascular tissues, as well as many types of tumor cells. Thus, these fish-derived peptides appear to play important roles in human physiology, such as appetite regulation, stress response and cardiovascular regulation, and also in diseases, for example, obesity, cardiovascular diseases and tumors. Development of antagonists/agonists against the receptors for these peptides may open new strategies for the treatment of various diseases, including obesity-related diseases, hypertension, heart failure and malignant tumors. IN the last century, a large number of peptide hormones were discovered. Some of the novel peptides are produced and secreted by classically non-endocrine organs, such as brain, heart and vascular vessels [1], while some were originally discovered in non-mammalian species including fishes. The peptides produced by classically non-endocrine organs include hypothalamic hormones and various neuropeptides secreted by neurons [2-5], atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) by heart [6] and endothelins by vascular endothelium [7]. Some peptides appear to be ubiquitously expressed. For example, adrenomedullin, a vasodilator peptide discovered from pheochromocytoma tissue, is produced and secreted by various types of normal cells [1,8,9,10], such as fibroblasts [10], macrophages [10,11], glial cells [12] and retinal pigment epithelial cells [13,14], and by various tumor cells [1,[15][16][17][18][19]. Endothelin-1 is also ubiquitously expressed like adrenomedullin although it was originally isolated from aortic endothelial cells [7, 20, 21]. Thus, a large number of studies on hormones now aim not only at classical endocrine organs, but also at nonendocrine organs, such as cardiovascular organs.Another important aspect of the recent advances in peptide endocrinology is recognition of the importance of fish-derived hormones in human physiology and diseases. In this review, I will discuss three bioactive peptides: melanin-concentrating hormone (MCH) [22], urotensin-I [23, 24] and urotensin-II [25, 26]. These three peptides were originally discovered in fishes, and are now recognized to have very important physiological roles in mammals including human. Furt...

Human Urotensin II as a Link between Hypertension and Coronary Artery Disease

“…Tubular epithelial cells obtained at nephrectomy from patients with diabetic nephropathy showed overexpression of U-II and UT receptor (27). In the presence of diabetes mellitus, U-II may also be associated with obesity (28). Intracerebroventricular administration of U-II into sheep causes hyperglycemia, which may be mediated by U-II-stimulated increases in circulating levels of epinephrine and cortisol (29).…”

Fish derived bio-active peptides and their metabolic effects

“…It also can be found in mammalians central nervous system as a cyclic neuropeptide which has roles in complex network of stress-regulating system and appetite stimulating (Kawauchi et al, 1983;Flier, 2004;. Takahashi et al(2004) have reported salmon and human MCH sequencing ( Fig.1). MCH is stimulator on food intake, may cause to obesity.…”

Distribution of Urocortins and Corticotropin-Releasing Factor Receptors in the Cardiovascular System

“…Urocortins (Ucns) were shown to be expressed in various tissues and cells of the human, such as brain, pituitary, gastrointestinal tract, ovary, placenta, synovial tissue, lymphocytes, and skin [16–28]. …”