Aging and the neuroendocrine regulation of reproduction and body weight

Aging in men is associated with a decline in trophic factors such as testos terone (T), alterations in body composition and impaired energy and body we ight regulation. We performed studies to investigate the mechanisms underly ing age-related changes in the neuroendocrine control of testis function, b ody composition, food intake and body weight in the Brown Norway (BN) rat. We found that similar to aging men, male BN rats demonstrate both primary a nd secondary testicular failure with aging without confounding age-related tumors, hormonal changes and systemic illnesses. With aging, these animals have blunted circadian variations in luteinizing hormone (LH) and T, and de creased hypothalamic,gonadotropin-releasing hormone (GnRH) synthetic capaci ty with preserved pituitary gonadotropin responses to GnRH. We found that a ging male BN rats have increased peripheral and visceral adiposity associat ed with increased insulin and leptin levels, and decreased relative lean bo dy mass and muscle mass. We found that these rats exhibit reduced food inta ke and body weight gain associated with decreased hypothalamic neuropeptide Y (NPY) gene expression in the arcuate nucleus (ARC), both during ad-libit um feeding and after a 72-h fast. Recently, we found that old male BN rats treated chronically with troglitazone, an insulin sensitizer, lowered high insulin and leptin levels, decreased body fat, and corrected the blunted fo od intake and body weight gain response to fasting without affecting basal ARC NPY gene expression. These findings suggested that hyperinsulinemia and /or hyperleptinemia associated with aging may contribute to the age-related impairment in energy and weight regulation. Our studies suggest that the a ging male BN rat is an excellent model to investigate the mechanisms underl ying the age-associated changes in the neuroendocrine control of body compo sition, energy intake and body weight. (C) 2000 Elsevier Science Inc. All r ights reserved.