The Effect Of Ghrelin, Leptin And Orexins On The Function Of Pituitary Somatotropes In Rat, Mouse And Human.
Funder
National Health and Medical Research Council
Funding Amount
$447,000.00
Summary
Malnutrition such as obesity or wasting syndrome is accompanied by GH deficiency. Three newly discovered metabolic regulatory hormones, leptin from fat tissue, ghrelin from stomach and orexins from hypothalamus, play important roles in regulating appetite, energy expenditure, and adiposity. Receptors for three metabolic regulatory hormones are all present in pituitary GH secreting cells (somatotropes) and accumulated laboratory data indicate a modification of GH secretion by three hormones. Cont ....Malnutrition such as obesity or wasting syndrome is accompanied by GH deficiency. Three newly discovered metabolic regulatory hormones, leptin from fat tissue, ghrelin from stomach and orexins from hypothalamus, play important roles in regulating appetite, energy expenditure, and adiposity. Receptors for three metabolic regulatory hormones are all present in pituitary GH secreting cells (somatotropes) and accumulated laboratory data indicate a modification of GH secretion by three hormones. Contradictory results have however been reported. Mechanisms of action of these three hormones are not clear and the interrelationship between metabolic regulatory hormones and intrinsic GH regulatory system is unknown. We propose to clarify this issue by investigating the effect of in vivo treatment of mice and in vitro treatment of cultured pituitary cells with leptin, ghrelin, and orexins. GH secretion, GH and GH-regulatory hormones' receptor synthesis in pituitary somatotropes will be measured. We will also use GH-GFP transgenic mice, in which somatotropes are specifically marked with green fluorescent signal, to study morphological change of somatotropes in mouse pituitary glands after in vivo treatment. By completing this project, we will be able (1) to clarify the physiological role of metabolic regulatory hormones in control of GH levels and (2) to clarify the pathological role of metabolic regulatory hormones in GH deficiency occurred in malnutritional conditions.Read moreRead less
In the normal process of hearing, the brain actively selects sounds of interest from competing background sounds. This normal auditory function is indispensible for children and adults to cope in non-optimal listening environments, however the mechanisms by which such performance is achieved are poorly understood. This project will investigate the nerve circuits that enable this to occur and will also investigate how these circuits malfunction in various types of partial deafness. The results wi ....In the normal process of hearing, the brain actively selects sounds of interest from competing background sounds. This normal auditory function is indispensible for children and adults to cope in non-optimal listening environments, however the mechanisms by which such performance is achieved are poorly understood. This project will investigate the nerve circuits that enable this to occur and will also investigate how these circuits malfunction in various types of partial deafness. The results will improve our understanding of how we detect sounds and the impact of hearing pathologies on this process.Read moreRead less