Oral Presentation The International Congress of Neuroendocrinology 2014

NPY neurons as a critical hypothalamic neuronal node for the control of GH release relative to food intake  (#125)

L Huang 1 , HY Tan 1 , MJ Fogarty 1 , ZB Andrews 2 , JD Veldhuis 3 , H Herzog 4 , C Chen 1 , Frederik Steyn 1
  1. School of Biomedical Sciences, University of Queensland, St Lucia, Brisbane, Queensland, 4072, Australia
  2. Department of Physiology, Monash University , Clayton, Victoria, 3183, Australia
  3. Department of Medicine, Endocrine Research Unit, Mayo School of Graduate Medical Education, Clinical Translational Science Center, Mayo Clinic, Rochester, MN 55905, USA
  4. Neuroscience Research Program, Garvan Institute of Medical Research, St Vincent’s Hospital, Darlinghurst, Sydney, New South Wales , Australia

Neuropeptide-Y (NPY) expressing neurons are orexigenic neurons that sense negative energy balance and engage neural mechanisms to restore energy balance by increasing food intake and decreasing energy expenditure. We previously documented the suppression of pulsatile GH secretion in the fasting mouse, and demonstrated that this occurs alongside a rise in hypothalamic NPY and somatostatin mRNA expression. Given anticipated interactions between NPY and somatostatin neurons, we proposed that NPY neurons act through somatostatin neurons to suppress GH release in the fasting mouse.

We confirmed interactions between somatostatin and NPY expressing neurons in the mouse by demonstrating synaptic sites between NPY fibres and somatostatin positive projections within the periventricular nucleus. Using NPY-deficient (NPYKO) mice, we demonstrate the complete recovery of pulsatile GH release in fasting mice. Importantly, GH pulsatility in NPYKO mice did not change under fed conditions, suggesting that NPY neurons primarily participate in GH release during negative energy balance. NPY exerts its effects through multiple NPY-responsive receptors (Y-receptors). The Y1 receptor (Y1R) is the dominant postsynaptic receptor, whereas the Y2 receptor (Y2R) is mainly expressed presynaptically on NPY neurons. We confirmed the recovery of pulsatile GH release in fasting germ-line deleted Y1R (Y1RKO) mice, whereas germ-line deletion of the Y2R (Y2RKO mice) did not recover the fasting-induced suppression of GH release. Rather, we observed a significant reduction in peak GH secretion in ad libitum fed Y2RKO mice.

Observations confirm that NPY suppresses GH secretion in the mouse through postsynaptic interactions with the Y1 receptor. As NPY neurons do not participate in the regulation of GH pulsatility under fed conditions, we propose that the Y2R contributes to GH release independent of NPY. Collectively, observations demonstrate that NPY neurons, acting through somatostatin neurons, are a key sensory node integrating metabolic information between the body and hypothalamic regulators of GH release.