Oral Presentation 2014 International Biophysics Congress

Regulation of Growth Hormone Pulsatility by Metabolic Homeostasis through Hypothalamic-Pituitary Somatic Axis (#101)

Chen Chen 1
  1. Department of Reproduction and Infertility, Chengdu Women's and Children's Central Hospital, Chengdu, Sichuan, China

Growth hormone (GH) modulates lipogenesis and lipolysis under positive and negative energy balances. It is thought that impaired GH secretion in response to dietary induced weight gain contributes to insulin-induced lipogenesis and maintenance of normal plasma non-esterified free fatty acid (NEFA) levels. GH secretion is also reduced in response to negative energy balance, probably to keep a minimum metabolic expenditure during energy deficiency. Mechanisms underlying the reduction in GH are not clear and single time point GH measurement is misleading to reflect true pulsatile GH levels. To assess the mechanisms, we investigated the relationship between pulsatile GH secretion and food intake, as well as dietary affected body weight, fat mass, circulating levels of insulin, glucose and non-esterified free fatty acids (NEFAs) in male mice with or without genetic modifications of hypothalamic feeding center’s melanocortin and neuropeptide Y systems. During positive energy balance, data confirms an inverse relationship between circulating levels of GH in pulse and insulin, and the corresponding maintenance of circulating levels of NEFAs and glucose. Moreover, observations demonstrate the potential role for insulin in sustaining low pulse levels of GH following progressive weight gain, and in obesity. We propose that suppressed GH secretion in obesity is an adaptation at hypothalamus to maintain normal NEFA and glucose levels under unhealthy positive energy balance. During negative energy balance, we demonstrate the involvement of NPY and receptor systems in causing inhibition of GH secretion, probably through a stimulation of hypothalamic somatostatin release into medium eminence. NPY system may be activated by a reduction in circulating glucose levels. Both Y1 and Y2 receptors have been involved in the regulation of GH using specific KO mouse models. Our work indicates that peripheral metabolic homeostasis regulate GH profiles to maintain a healthier condition through hypothalamic-pituitary somatic axis.