The identification of leptin as a gene product produced in fat revitalised interest in the means by which the brain receives signals to regulate appetite, energy expenditure and the neuroendocrine system. We have studied the effects of alterations in bodyweight on the expression of appetite regulating peptides in the brain and have also determined effects of leptin on a range of parameters in the hypothalamus and pituitary gland of the ovariectomised female sheep. Intracerebroventricular (icv) infusion of leptin had little effect on the secretion of hormones in the normally fed animal but restored the secretion of luteinising hormone (LH), growth hormone (GH) and cortisol in fasted animals. Infusion (icv) of leptin restored LH secretion in underfed animals. Leptin had a negative effect on the secretion of GH from somatotrophs in primary culture. To define the pathway by which leptin affects the neuroendocrine system we have delineated the types of cells that express the leptin receptor in the hypothalamus and pituitary gland. Since leptin is produced by fat, we developed models of long-term alteration in bodyweight and then quantified changes in gene expression that occur in the hypothalamus using in situ hybridisation. Effects were observed in a number of hypothalamic nuclei and we have attempted to relate these to appetite regulation and neuroendocrine function. Immunohistochemistry has provided information on the extent to which appetite regulating systems interact with neuroendocrine cells. In addition, a seasonal model in sheep has given insight to the way that leptin may regulate appetite and perhaps the neuroendocrine system. In particular, there are seasonal variations in voluntary food intake that correlate with the sensitivity of the brain to leptin. These studies provide insight to the physiology of leptin especially in relation to the endocrine system.
03 - 04 Dec 2001
Society for Endocrinology