title: Actions of NPY, and its Y1 and Y2 receptors on pulsatile growth hormone secretion during the fed and fasted state.
abstract: The hypothalamic NPY system plays an important role in regulating food intake and energy expenditure. Different biological actions of NPY are assigned to NPY receptor subtypes. Recent studies demonstrated a close relationship between food intake and growth hormone (GH) secretion; however, the mechanism through which endogenous NPY modulates GH release remains unknown. Moreover, conclusive evidence demonstrating a role for NPY and Y-receptors in regulating the endogenous pulsatile release of GH does not exist. We used genetically modified mice (germline Npy, Y1, and Y2 receptor knock-out mice) to assess pulsatile GH secretion under both fed and fasting conditions. Deletion of NPY did not impact fed GH release; however, it reversed the fasting-induced suppression of pulsatile GH secretion. The recovery of GH secretion was associated with a reduction in hypothalamic somatotropin release inhibiting factor (Srif; somatostatin) mRNA expression. Moreover, observations revealed a differential role for Y1 and Y2 receptors, wherein the postsynaptic Y1 receptor suppresses GH secretion in fasting. In contrast, the presynaptic Y2 receptor maintains normal GH output under long-term ad libitum-fed conditions. These data demonstrate an integrated neural circuit that modulates GH release relative to food intake, and provide essential information to address the differential roles of Y1 and Y2 receptors in regulating the release of GH under fed and fasting states.
authors.affiliation: School of Biomedical Sciences, University of Queensland, St. Lucia, Brisbane, Queensland, 4072 Australia.
authors.forename: Lili
authors.initials: L
authors.lastname: Huang
authors.affiliation: School of Biomedical Sciences, University of Queensland, St. Lucia, Brisbane, Queensland, 4072 Australia.
authors.forename: Hwee Y
authors.initials: HY
authors.lastname: Tan
authors.affiliation: School of Biomedical Sciences, University of Queensland, St. Lucia, Brisbane, Queensland, 4072 Australia.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Fogarty
authors.affiliation: Department of Physiology, Monash University, Clayton, Victoria, 3183 Australia.
authors.forename: Zane B
authors.initials: ZB
authors.lastname: Andrews
authors.affiliation: Department of Medicine, Endocrine Research Unit, Mayo School of Graduate Medical Education, Clinical Translational Science Center, Mayo Clinic, Rochester, Minnesota 55905, and.
authors.forename: Johannes D
authors.initials: JD
authors.lastname: Veldhuis
authors.affiliation: Neuroscience Research Program, Garvan Institute of Medical Research, St. Vincent's Hospital, Darlinghurst, Sydney, New South Wales, 2010 Australia.
authors.forename: Herbert
authors.initials: H
authors.lastname: Herzog
authors.affiliation: School of Biomedical Sciences, University of Queensland, St. Lucia, Brisbane, Queensland, 4072 Australia, f.steyn@uq.edu.au chen.chen@uq.edu.au.
authors.forename: Frederik J
authors.initials: FJ
authors.lastname: Steyn
authors.affiliation: School of Biomedical Sciences, University of Queensland, St. Lucia, Brisbane, Queensland, 4072 Australia, f.steyn@uq.edu.au chen.chen@uq.edu.au.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
mesh_terms: D000818:Animals; D001786:Blood Glucose; D005215:Fasting / Q000502:physiology*; D013006:Growth Hormone / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000096:biosynthesis; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009478:Neuropeptide Y / Q000097:blood / Q000235:genetics / Q000502:physiology*; D019894:Peptide YY / Q000097:blood; D017476:Receptors, Neuropeptide Y / Q000235:genetics / Q000502:physiology*; D013004:Somatostatin / Q000096:biosynthesis
chemical_list: D001786:Blood Glucose; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; C095889:neuropeptide Y2 receptor; D019894:Peptide YY; D013004:Somatostatin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone
keywords: NPY; NPY-receptors; fasting; feeding; growth hormone; somatostatin