Extension Number

ASL R1778

Topic

Breeding/Physiology

Publication Date

2002

Abstract

Endocrine regulation in the brain is important for body growth and metabolism both in human and domestic animals. Growth hormone (GH) has been recognized as a primary regulator that plays an important role in determining body composition to maintain beneficial ratio between skeletal muscle and fat. The main targets of GH actions are liver, muscle, and bone where this action is partially mediated through an increase in insulin-like growth factor-_ (IGF-_). A role for GH in the brain is more critically approached because its pulsatile secretion is regulated by dual system of hypothalamic control: a positive/negative feedback loop. Growth hormonereleasing hormone (GHRH) is released from arcuate neurons in the hypothalamus and transported through the portal blood vessels into the pituitary gland, where it stimulates GH release from somatotrophs (GH-secreting cells in the pituitary gland). Negative feedback is mediated by the release of somatostatin (SS) from hypothalamic neurons that act to inhibit GH release. A third endocrine pathway controlling GH secretion has been led by discovery of the GH secretagogues (GHSs); growth hormone-releasing peptides (GHRPs) and their pharmacological nonpeptidyl analogs that have a direct effect on in vitro pituitary GH release in both animal and human somatotrophs. GHSs synergize with GHRH and functionally antagonize SS acting on the hypothalamus for GH secretion. Alterations in GH pulsatility are seen in a variety of physiological and pathological circumstances, including puberty, aging, estrous cycle, obesity, starvation, and growth delay. Disconnection of hypothalamic-pituitary stalk results in loss of normal GH pulsatility and suggests that pulsatility is regulated by changes in GHRH, SS, and a natural ligand for GHS receptor. GHSs administrated alone or in combination with GHRH are the most potent and reproducible GH releasers, and useful tools for the diagnosis of GH deficiency when tested in a variety of pathological condition in patients and across many species. Therefore, GHSs present a factor for extending the understanding of GH secretion, as well as a unique therapeutic opportunity. Neuropeptide Y (NPY) has been well known mediators not only in GH-secreting mechanism by GHSs but also in food intake -relating network in hypothalamic neurons. Previous studies suggest that NPY has negative feedback effect of GH release and stimulatory action in the regulation of appetite having reciprocal relation with hypothalamic hormone such as GHRH, SS, GHS and leptin. In addition to stimulating body growth, alterations in nutritional status such as obesity or food deprivation significantly influence GH secretion. Leptin secreted by adipocytes that regulates food intake and energy expenditure has recently been shown to play a stimulatory role on GH secretion. Leptin induced GH secretion is suppressed by NPY, so it is possible that NPY mediates leptin action in the hypothalamus. Another candidate for GH regulation in the hypothalamic area is ghrelin, a GH-releasing acylated peptide as an endogenous bioactive ligand for the GHS receptor. Ghrelin produced by stomach, intestine, placenta, pituitary, and possibly in the hypothalamus is a recently discovered hormone that plays a critical role in the maintenance of energy homeostasis as well as the stimulation of GH release. GH secretion results from a complex series of interactions that occur both in peripheral tissue and in the central nervous system (CNS). The regulation of growth by elements of the GH axis is a complex process that we have only begun to understand. Further evaluation of physiology and genes involved in the production, secretion, and actions of GH will enhance our understanding of the role and central mechanisms of endocrine regulation affecting growth

Copyright Owner

Iowa State University

Language

en

File Format

application/pdf

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