GH-related and extra-endocrine actions of GH secretagogues in aging

• Published in: Neurobiology of aging Vol. 23; no. 5; pp. 907 - 919
• Main Authors: Muller, Eugenio E, Rigamonti, Antonello E, Colonna, Vito De Gennaro, Locatelli, Vittorio, Berti, Ferruccio, Cella, Silvano G
• Format: Journal Article Conference Proceeding
• Language: English
• Published: London Elsevier Inc 01.09.2002; Elsevier Science
• Subjects: Aged; Aging; Aging - metabolism; Biological and medical sciences; Endocrine System - metabolism; Fundamental and applied biological sciences. Psychology; Ghrelin; Growth hormone; Growth hormone secretagogue extra-endocrine actions; Growth hormone secretagogues; Growth hormone secretagogues in aging; Growth hormone-releasing hormone; Growth Hormone-Releasing Hormone - metabolism; Hormones and neuropeptides. Regulation; Human Growth Hormone - metabolism; Humans; Hypothalamus. Hypophysis. Epiphysis. Urophysis; Peptide Hormones - metabolism; Somatostatin; Vertebrates: endocrinology; Growth hormone secretagogue extra-endocrine actions; Growth hormone-releasing hormone; Ghrelin; Aging; Somatostatin; Growth hormone secretagogues; Growth hormone; Growth hormone secretagogues in aging; Senescence; Review; Adenohypophyseal hormone; Somatotropin hormone
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/S0197-4580(02)00026-X

Growth hormone (GH) secretion declines with aging in mammals, including humans. Defective pituitary function does not play a major role in this event. Rather, age-related changes involving the function of specific hypothalamic peptides for GH regulation, GH-releasing hormone (GHRH) and somatostatin (SS), appear to be the fundamental factors. Experimental evidence indicates that GHRH synthesis is impaired with aging in the rat hypothalamus, and that a relative hyperfunction of the SS-ergic system is present. In the elderly, systemic, short-term administration of GHRH enhances GH secretion and increases the formation of the GH-dependent peptide IGF-1. In old dogs, a combination of GHRH and clonidine (CLO), an α 2-adrenoceptor agonist, reportedly acting via GHRH stimulation and SS inhibition, is the most effective stimulus to rejuvenate the apulsatile GH secretion. Discovery of GH secretagogues (GHSs), a series of peptydil and non-peptydil synthetic molecules endowed with a strong GH-releasing activity, the cloning of a GHS receptor (GHS-R), present in the hypothalamus and the pituitary, the isolation of the endogenous ligand of GHS-R, ghrelin, a 28-amino acid peptide whose main source is the stomach, pose the issue for the physiologic role of the GHS/ghrelin system and forces revision of our current understanding of GH regulation in different GH deficiency (GHD) states, including aging. GHSs are very effective for enhancing GH secretion in old subjects, but long-term studies are needed to assess their safety and the real biological impact of GHS replacement therapy in aging. Therapeutic use of GHSs can also be envisaged to restore, via GH-independendent mechanisms, functional, and structural age-related alterations, such as anorexia, sexual dysfunction, cardiovascular damage, bone loss.