PHYSIOLOGY OF THE PROLACTIN RELEASING PEPTIDES

Summary

Principal Investigator: WILLIS SAMSON
Affiliation: Saint Louis University
Country: USA
Abstract: DESCRIPTION (provided by applicant): This is a rerevised, competitive renewal application (HL66023) that continues our examination of the physiologic relevance of recently described neuropeptides which we have demonstrated to act at least pharmacologically to stimulate stress hormone secretion (prolactin, PRL, and adrenocorticotropin, ACTH) by a brain site of action. Additionally, these peptides stimulate stress-related behavioral responses (activity) and at least one acts in brain to stimulate sympathetic activity resulting in increased blood pressure. These peptides (prolactin releasing peptide, PrRP;neuropeptide W, NPW;and neuropeptide B, NPB) are produced in separate populations of neurons in brain, many of which innervate the hypothalamic paraventricular nucleus (PVN), arcuate nucleus (ARC) and ventromedial and dorsomedial hypothalamic nuclei (VMH/DMH). All three peptides are contained in neurons that innervate autonomic centers in hypothalamus and brain stem. It is our goal to understand the roles these peptides play in the hypothalamic and extrahypothalamic responses to stress. We address multiple specific aims all related to the founding hypothesis that one or more of these peptides is essential for the endocrine and/or cardiovascular response to stress, under certain paradigms of stress. Our approach will be to demonstrate direct effects of these peptides on identified fore- and hindbrain neurons [e.g. in PVN, ARC, VMH/DMH, nucleus tractus solitarius (NTS), rostral lateral medulla (RVLM), and dorsal motor nucleus of the Vagus] using electrophysiologic, pharmacologic and single cell RT- PCR approaches. We will then attempt compromise of peptide production and examine hormone secretion in response to physical stress and the cardiovascular response to hypertensive and hypotensive challenge (i.e. baroreflex sensitivity). Understanding the normal mechanisms controlling the response to stress will reveal potential strategies for the management of stress in the human population and the cardiovascular and metabolic consequences of that stress. These studies may also provide insight into the central mechanisms contributing to development of the metabolic syndrome (Syndrome X), which is characterized by obesity, poor glycemic control, altered metabolic and autonomic function and a propensity for adverse cardiovascular outcomes. Additionally, these studies will provide further insight into the coordinated hormonal and autonomic responses to stress.
Funding Period: ----------------2001 - ---------------2011-
more information: NIH RePORT

Top Publications

  1. ncbi Intermedin/Adrenomedullin-2 inhibits growth hormone release from cultured, primary anterior pituitary cells
    Meghan M Taylor
    Saint Louis University, Pharmacological and Physiological Science, Missouri 63104, USA
    Endocrinology 147:859-64. 2006
  2. pmc Selective inhibition of angiotensin receptor signaling through Erk1/2 pathway by a novel peptide
    Jun Liu
    Division of Nephrology and Hypertension, Department of Medicine, Georgetown University, Washington, D C
    Am J Physiol Regul Integr Comp Physiol 306:R619-26. 2014
  3. pmc Compromise of Endogenous Neuropeptide W Production Abrogates the Dipsogenic and Pressor Effects of Angiotensin II in Adult Male Rats
    A T Pate
    Department of Pharmacological and Physiological Science, Saint Louis University, Saint Louis, MO, USA
    J Neuroendocrinol 25:1290-7. 2013
  4. ncbi Evidence for an interaction between proinsulin C-peptide and GPR146
    Gina L C Yosten
    Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, 1402 S Grand Boulevard, Saint Louis, Missouri 63104, USA
    J Endocrinol 218:B1-8. 2013
  5. pmc Neuropeptide W increases mean arterial pressure as a result of behavioral arousal
    Alicia T Pate
    Department of Pharmacological and Physiological Science, Saint Louis University, St Louis, Missouri
    Am J Physiol Regul Integr Comp Physiol 305:R804-10. 2013
  6. ncbi Evidence for an interaction between proinsulin C-peptide and GPR146
    Gina L C Yosten
    Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, 1402 S Grand Boulevard, Saint Louis, Missouri 63104, USA
    J Endocrinol 218:B1-8. 2013
  7. pmc A novel reproductive peptide, phoenixin
    G L C Yosten
    Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St Louis, MO 63104, USA
    J Neuroendocrinol 25:206-15. 2013
  8. pmc Neural circuitry underlying the central hypertensive action of nesfatin-1: melanocortins, corticotropin-releasing hormone, and oxytocin
    Gina L C Yosten
    Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, Saint Louis, Missouri
    Am J Physiol Regul Integr Comp Physiol 306:R722-7. 2014
  9. pmc Nesfatin-1 inhibits NPY neurons in the arcuate nucleus
    Christopher J Price
    Department of Physiology, Queen s University, Kingston, ON, Canada, K7L 3N6
    Brain Res 1230:99-106. 2008
  10. ncbi Prolactin releasing peptide (PrRP): an endogenous regulator of cell growth
    Willis K Samson
    Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, 1402 South Grand Boulevard, St Louis, MO 63104, USA
    Peptides 27:1099-103. 2006

Scientific Experts

  • Gina L C Yosten
  • WILLIS SAMSON
  • Meghan M White
  • Christopher J Price
  • Alastair V Ferguson
  • Jun Liu
  • A T Pate
  • Alicia T Pate
  • C J Price
  • Meghan M Taylor
  • Kathryn Sandberg
  • Dan Zhang
  • Wei Zheng
  • Robert C Speth
  • Hong Ji
  • A V Ferguson
  • Kevin J Latchford
  • Sara L Bagley

Detail Information

Publications23

  1. ncbi Intermedin/Adrenomedullin-2 inhibits growth hormone release from cultured, primary anterior pituitary cells
    Meghan M Taylor
    Saint Louis University, Pharmacological and Physiological Science, Missouri 63104, USA
    Endocrinology 147:859-64. 2006
    ....
  2. pmc Selective inhibition of angiotensin receptor signaling through Erk1/2 pathway by a novel peptide
    Jun Liu
    Division of Nephrology and Hypertension, Department of Medicine, Georgetown University, Washington, D C
    Am J Physiol Regul Integr Comp Physiol 306:R619-26. 2014
    ....
  3. pmc Compromise of Endogenous Neuropeptide W Production Abrogates the Dipsogenic and Pressor Effects of Angiotensin II in Adult Male Rats
    A T Pate
    Department of Pharmacological and Physiological Science, Saint Louis University, Saint Louis, MO, USA
    J Neuroendocrinol 25:1290-7. 2013
    ..In addition, NPW-producing neurones appear to participate in the hypothalamic mechanisms controlling prolactin (but not corticosterone) secretion. ..
  4. ncbi Evidence for an interaction between proinsulin C-peptide and GPR146
    Gina L C Yosten
    Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, 1402 S Grand Boulevard, Saint Louis, Missouri 63104, USA
    J Endocrinol 218:B1-8. 2013
    ..These data indicate that GPR146 is likely a part of the C-peptide signaling complex and provide a platform for the elucidation of the C-peptide signalosome...
  5. pmc Neuropeptide W increases mean arterial pressure as a result of behavioral arousal
    Alicia T Pate
    Department of Pharmacological and Physiological Science, Saint Louis University, St Louis, Missouri
    Am J Physiol Regul Integr Comp Physiol 305:R804-10. 2013
    ..Our results suggest that NPW increased MAP secondary to increased behavioral arousal...
  6. ncbi Evidence for an interaction between proinsulin C-peptide and GPR146
    Gina L C Yosten
    Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, 1402 S Grand Boulevard, Saint Louis, Missouri 63104, USA
    J Endocrinol 218:B1-8. 2013
    ..These data indicate that GPR146 is likely a part of the C-peptide signaling complex and provide a platform for the elucidation of the C-peptide signalosome. ..
  7. pmc A novel reproductive peptide, phoenixin
    G L C Yosten
    Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St Louis, MO 63104, USA
    J Neuroendocrinol 25:206-15. 2013
    ..Phoenixin may represent a new class of hypothalamically-derived pituitary priming factors that sensitise the pituitary to the action of other RFs, rather than directly stimulating the fusion of secretary vesicles to pituitary membranes...
  8. pmc Neural circuitry underlying the central hypertensive action of nesfatin-1: melanocortins, corticotropin-releasing hormone, and oxytocin
    Gina L C Yosten
    Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, Saint Louis, Missouri
    Am J Physiol Regul Integr Comp Physiol 306:R722-7. 2014
    ....
  9. pmc Nesfatin-1 inhibits NPY neurons in the arcuate nucleus
    Christopher J Price
    Department of Physiology, Queen s University, Kingston, ON, Canada, K7L 3N6
    Brain Res 1230:99-106. 2008
    ..Therefore, nesfatin-1-induced inhibition of feeding may be mediated through the inhibition of orexigenic NPY neurons...
  10. ncbi Prolactin releasing peptide (PrRP): an endogenous regulator of cell growth
    Willis K Samson
    Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, 1402 South Grand Boulevard, St Louis, MO 63104, USA
    Peptides 27:1099-103. 2006
    ....
  11. ncbi Intermedin 17-47 does not function as a full intermedin antagonist within the central nervous system or pituitary
    Meghan M White
    Saint Louis University, School of Medicine, Department of Pharmacological and Physiological Science, 1402 S Grand Boulevard, St Louis, MO 63104, USA
    Peptides 28:2171-8. 2007
    ..c.v. administration, cause increased water drinking in male rats. This tool may provide a better method than the use of the IMD17-47 compound to study the role of endogenous IMD within the CNS and pituitary...
  12. ncbi Neuropeptide W influences the excitability of neurons in the rat hypothalamic arcuate nucleus
    Christopher J Price
    Department of Physiology, Queen s University, Kingston, Ont, Canada
    Neuroendocrinology 88:88-94. 2008
    ....
  13. ncbi Obestatin inhibits vasopressin secretion: evidence for a physiological action in the control of fluid homeostasis
    Willis K Samson
    Department of Pharmacological and Physiological Science, Saint Louis University, 1402 South Grand Boulevard, St Louis, Missouri 63104, USA
    J Endocrinol 196:559-64. 2008
    ..We conclude that this product of post-translational processing of the ghrelin prohormone may be an important contributor to the physiologic regulation of fluid and electrolyte homeostasis...
  14. pmc The paraventricular nucleus of the hypothalamus - a potential target for integrative treatment of autonomic dysfunction
    Alastair V Ferguson
    Queen s University, Department of Physiology, Kingston, Ontario, K7L 3N6, Canada
    Expert Opin Ther Targets 12:717-27. 2008
    ....
  15. pmc Neuronostatin encoded by the somatostatin gene regulates neuronal, cardiovascular, and metabolic functions
    Willis K Samson
    Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St Louis, Missouri 63104, USA
    J Biol Chem 283:31949-59. 2008
    ..Our findings demonstrate diverse neuronal, neuroendocrine, and cardiovascular actions of a somatostatin gene-encoded hormone and provide the basis to investigate the physiological roles of this endogenously produced brain/gut peptide...
  16. pmc Neuropeptide W has cell phenotype-specific effects on the excitability of different subpopulations of paraventricular nucleus neurones
    C J Price
    Department of Physiology, Queen s University, Kingston, Ontario, Canada
    J Neuroendocrinol 21:850-7. 2009
    ..The demonstration of particular phenotypic populations of PVN neurones showing NPW-induced effects on excitability reinforces the importance of the NPB/NPW neuropeptide system as a regulator of autonomic function...
  17. pmc Neuronostatin acts in brain to biphasically increase mean arterial pressure through sympatho-activation followed by vasopressin secretion: the role of melanocortin receptors
    Gina L C Yosten
    Dept of Pharmacological and Physiological Science, Saint Louis University, St Louis, MO 63104, USA
    Am J Physiol Regul Integr Comp Physiol 300:R1194-9. 2011
    ....
  18. pmc The melanocortins, not oxytocin, mediate the anorexigenic and antidipsogenic effects of neuronostatin
    Gina L C Yosten
    Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, 1402 S Grand Boulevard, Saint Louis, MO 63104, USA
    Peptides 31:1711-4. 2010
    ..Neuronostatin-induced anorexia was not reversed by pretreatment with the oxytocin receptor antagonist, OVT, suggesting that neuronostatin acts through a unique subset of POMC neurons that do not signal via central oxytocin receptors...
  19. pmc The evolving story of orexin biology: the hits keep coming
    Willis K Samson
    Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine 1402 South Grand Boulevard, St Louis, MO 63104 USA
    F1000 Biol Rep 1:85. 2009
    ..Highlights from recently published novel approaches and findings are reviewed here...
  20. pmc Nesfatin-1 exerts cardiovascular actions in brain: possible interaction with the central melanocortin system
    Gina L C Yosten
    Saint Louis Univ, Dept of Pharmacological and Physiological Science, 1402 S Grand Blvd, St Louis, MO 63104, USA
    Am J Physiol Regul Integr Comp Physiol 297:R330-6. 2009
    ..Thus we have identified a novel action of nesfatin-1, in addition to its anorexigenic effects, to stimulate autonomic nervous system activity...
  21. ncbi A possible relationship between brain-derived adrenomedullin and oxytocin in the regulation of sodium balance
    Meghan M White
    Department of Pharmacological and Physiological Science, St Louis University School of Medicine, St Louis, Missouri 63104, USA
    J Endocrinol 203:253-62. 2009
    ....
  22. pmc The anorexigenic and hypertensive effects of nesfatin-1 are reversed by pretreatment with an oxytocin receptor antagonist
    Gina L C Yosten
    Department of Pharmacological and Physiological Science, Saint Louis University, Saint Louis, Missouri 63104, USA
    Am J Physiol Regul Integr Comp Physiol 298:R1642-7. 2010
    ....