Neuroendocrine control of appetite and reproduction in sheep
Reproductive neuroendocrine activity and appetite are modulated at the hypothalamus by both nutritional status and photoperiod in the seasonal animal. The objectives of this work were (1) to measure circulating hormones and/or metabolites that relay information about peripheral nutritional status to the hypothalamus, (2) to identify which hypothalamic neuropeptides and receptors that are responsive to photoperiodic and nutritional feedback and (3) to establish which changes in peripheral signals and/or hypothalamic neuropeptides are associated with alterations in the activity of the reproductive neuroendocrine axis. Three main experiments were carried out. The first experiment (Chapter 1) utilised a 2 x 2 design to examine the separate and interactive effects of photoperiod and food restriction on hypothalamic neuropeptide and receptor mRNA expression and on GnRH/LH secretion. In the second experiment (Chapter 2), two components of nutritional status, BC and increased food intake were investigated since both are positively related to reproductive performance in sheep. In the final experiment (Chapter 3) the approach was to use an exogenous treatment to artificially raise plasma insulin in an attempt to "drive" some of the foregoing effects. Collectively these studies have lead to the first localisation AgRp, MCH, orexin, Mc3R, Mc4R gene expression in the ovine hypothalamus. They indicate that circulating insulin and leptin are major factors relaying information about nutritional status to the hypothalamus. In addition, they have dissociated BC and food intake as signals to the hypothalamus. Moreover these studies have provided no evidence that NPY, AgRp, POMC, MCH and ObRb play a role in driving seasonal changes in appetite and gonadotrophin secretion. However they do suggest NPY-ergic and melanocortin pathways are important in maintaining appetite/bodyweight/energy homeostasis or restoring energy balance following perturbation. Furthermore the results show that changes in nutrient-sensitive hypothalamic neuropeptide and receptor gene expression may not necessarily lead to alterations in the activity of the reproductive neuroendocrine axis. However, they do indicate that increased NPY biosynthesis during food restriction may be involved in the inhibition of pulsatile GnRH/LH release.