The role of ghrelin in the neuroendocrine reproductive and appetite axes in sheep
Nutrition and photoperiod modulate appetite and reproductive neuroendocrine axes in seasonal animals like sheep. Stomach-derived ghrelin is implicated in both axes and this thesis examines its role in sheep. The first experiment describes immunolocalisation of ghrelin and its functional receptor (GHSR-la) in peripheral tissues (stomach, intestine, pancreas, liver and kidney), brain (hypothalamus), pituitary (all secretory cells) and gonads. Expression in testes was seasonally dependent, and levels of ghrelin expression in placenta paralleled the placental growth curve. The second experiment examined effects of intracerebroventricular (ICV) ghrelin administration. ICV ghrelin transiently increased food intake in long days (LD), but not in short days (SD), and decreased reproductive neuroendocrine (LH) output in SD, but not in LD. In both photoperiods, ICV ghrelin stimulated growth hormone (GH) release. Early response gene activation in hypothalamic neurones following ICV ghrelin suggested mediation of these responses via NPY and other pathways. The final experiment reports endogenous ghrelin concentrations during increasing (INP), decreasing (DNP) or static (SNP) nutritional status. Plasma LH, insulin and leptin were increased, constant and decreased, respectively, and GH concentrations decreased in INP sheep. However, plasma ghrelin concentrations were similar between groups, diurnally and over time. Collectively, these studies indicate that endogenous ghrelin is not a meal initiator in sheep and it does not play a key functional role regulating appetite, reproduction or GH secretion under "normal" physiological conditions. However, ghrelin may act as an emergency signal of acute nutritional demand, with photoperiod influencing hypothalamic responses. Additionally, ghrelin may be implicated in tissue development and function within the reproductive axis.