Orexins as neuroendocrine integrators between nutrition and reproduction control systems

Funded Activity Summary

Studies on humans and a range of animal species have shown that the effects of nutrition on reproduction are mediated at least partly by changes in the secretion of gonadotrophin releasing hormone (GnRH) and thus gonadotrophins. A number of metabolic signals must also be involved but those tested to date (glucose, insulin, leptin) do not seem to play major roles. Two exciting new candidates are orexin-A and orexin-B, a recently discovered pair of peptides that stimulate feeding behaviour. They are synthesized in the brain and, in rodents, they either stimulate or inhibit gonadotrophin secretion, depending on the presence of sex steroids. In this project, we will investigate the roles of the orexins as integrators of signals about gonadal activity, nutrition and body condition, all of which affect the activity of the reproductive control centres in the brain. We will use the mature male sheep because it shows clear and repeatable reproductive responses to changes in nutrition. We will locate the orexin-producing cells and the cells that respond to the orexins, and show how orexin production is affected by diet. We will also study the ways in which the orexins affect, and are affected by, the hormone systems that control reproduction and metabolism. Finally, we will try to find out why there are two orexins by looking at how their actions differ. Ultimately, the orexin system might explain the brain processes that are behind many of the reproductive problems that are associated with metabolic disorders, such as appetite loss, excessive exercise, undernutrition, polycystic ovarian syndrome, and insulin-dependent diabetes.

Funded Activity Details

Start Date: 01-01-2001

End Date: 01-01-2003

Funding Scheme: NHMRC Project Grants

Funding Amount: $332,036.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Other biomedical and clinical sciences not elsewhere classified

ANZSRC Socio-Economic Objective (SEO)

There are no SEO codes available for this funding activity

Other Keywords

anorexia nervosa, feeding disorders | diabetes | hypothalamic control of gonadotrophin release | interaction between sex steroid and diet | nutrition control of reproduction | orexin and orexin receptor | polycistic ovarian syndrome | reproductive dysfunction and fertility control

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