Review
Metabolic and stress-related roles of prolactin-releasing peptide

https://doi.org/10.1016/j.tem.2010.01.005Get rights and content

In the modern world, improvements in human health can be offset by unhealthy lifestyle factors, including the deleterious consequences of stress and obesity. For energy homeostasis, humoral factors and neural afferents from the gastrointestinal tract, in combination with long-term nutritional signals, communicate information to the brain to regulate energy intake and expenditure. Energy homeostasis and stress interact with each other, and stress affects both food intake and energy expenditure. Prolactin-releasing peptide, synthesized in discrete neuronal populations in the hypothalamus and brainstem, plays an important role in integrating these responses. This review describes how prolactin-releasing peptide neurons receive information concerning both internal metabolic states and environmental conditions, and play a key role in energy homeostasis and stress responses.

Section snippets

Prolactin-releasing peptide and its receptors

Prolactin-releasing peptide (PrRP) belongs to the family of RFamide peptides, which are defined by their common carboxy-terminal sequences, arginine (R) and amidated phenylalanine (F) residues [1]. PrRP was originally discovered as an endogenous ligand for G-protein-coupled receptor (GPR) 10 (also known as hGR3 and unknown hypothalamic receptor (UHR)-1), an orphan receptor, and at first, PrRP was thought to act at the pituitary gland as a hypothalamic releasing factor for prolactin secretion.

PrRP and short-term energy intake

Intracerebroventricular administration of PrRP reduces food intake [17], and both PrRP-deficient mice [14] and GPR10-deficient [15] mice are hyperphagic. Furthermore, acute blockade of PrRP signaling by an anti-PrRP neutralizing antibody induces hyperphagia [14]. The hyperphagia in PrRP-deficient mice or in rats injected with an anti-PrRP neutralizing antibody is caused by an increase in meal size rather than in meal frequency [14].

Meal size is regulated by satiety signals that terminate each

Conclusion

PrRP-expressing neurons receive information not only from short-term energy signals such as CCK but also from long-term metabolic signals such as leptin and estrogen (Figure 2). Disturbance of the PrRP–GPR10 system causes hyperphagia, leading to obesity and metabolic disorders. PrRP neurons also receive signals during stressful conditions and modulate stress responses in peripheral organs. PrRP also plays a role in stress-induced metabolic responses. The importance of PrRP for energy metabolism

Acknowledgements

This study was supported in part by the Japan Society for the Promotion of Science, the Ministry of Education, Culture, Sports, Science and Technology of Japan, the Danone Institute of Japan (the 2009 DIJ Research Grant), Japanese Society of Anti-Ageing Medicine and AstraZeneca KK (AstraZeneca Research Grant 2009). Research in GL's laboratory is supported by the BBSRC and the Wellcome Trust.

References (80)

  • Y. Takayanagi et al.

    Role of prolactin-releasing peptide in stress-induced energy expenditure

    Neurosci. Res.

    (2009)
  • T.H. Moran

    Unraveling the obesity of OLETF rats

    Physiol. Behav.

    (2008)
  • Y. Kataoka

    Gonadal regulation of PrRP mRNA expression in the nucleus tractus solitarius and ventral and lateral reticular nuclei of the rat

    Mol. Brain Res.

    (2001)
  • R. Tokita

    Prolactin secretion in response to prolactin-releasing peptide and the expression of the prolactin-releasing peptide gene in the medulla oblongata are estrogen dependent in rats

    Neurosci. Lett.

    (1999)
  • T. Mera

    Downregulation of prolactin-releasing peptide gene expression in the hypothalamus and brainstem of diabetic rats

    Peptides

    (2007)
  • K. Pacak

    Stress-induced norepinephrine release in the hypothalamic paraventricular nucleus and pituitary-adrenocortical and sympathoadrenal activity: in vivo microdialysis studies

    Front. Neuroendocrinol.

    (1995)
  • L.L. Zhu et al.

    Facilitative role of prolactin-releasing peptide neurons in oxytocin cell activation after conditioned-fear stimuli

    Neuroscience

    (2003)
  • T. Morales et al.

    Brainstem prolactin-releasing peptide neurons are sensitive to stress and lactation

    Neuroscience

    (2003)
  • T. Mera

    Prolactin-releasing peptide is a potent mediator of stress responses in the brain through the hypothalamic paraventricular nucleus

    Neuroscience

    (2006)
  • Y. Ibata

    Morphological survey of prolactin-releasing peptide and its receptor with special reference to their functional roles in the brain

    Neurosci. Res.

    (2000)
  • W.K. Samson

    A novel action of the newly described prolactin-releasing peptides: cardiovascular regulation

    Brain Res.

    (2000)
  • J. Horiuchi

    Effects of prolactin-releasing peptide microinjection into the ventrolateral medulla on arterial pressure and sympathetic activity in rats

    Brain Res.

    (2002)
  • M.L. Kalliomaki

    Prolactin-releasing peptide affects pain, allodynia and autonomic reflexes through medullary mechanisms

    Neuropharmacology

    (2004)
  • S.H. Lin

    Prolactin-releasing peptide (PrRP) promotes awakening and suppresses absence seizures

    Neuroscience

    (2002)
  • Y. Takayanagi et al.

    Effects of prolactin-releasing peptide administration upon anxiety-related behavior in rats

    Neurosci. Res.

    (2007)
  • Y. Yamamoto

    Increased anxiety behavior in OLETF rats without cholecystokinin-A receptor

    Brain Res. Bull.

    (2000)
  • A. Watanabe

    Altered emotional behaviors in the diabetes mellitus OLETF type 1 congenic rat

    Brain Res.

    (2007)
  • S.J. Torres et al.

    Relationship between stress, eating behavior, and obesity

    Nutrition.

    (2007)
  • A.G. Nieuwenhuizen et al.

    The hypothalamic-pituitary-adrenal-axis in the regulation of energy balance

    Physiol. Behav.

    (2008)
  • R. Coccurello

    Chronic social stress, hedonism and vulnerability to obesity: lessons from rodents

    Neurosci. Biobehav. Rev.

    (2009)
  • J.P. Warne

    Shaping the stress response: interplay of palatable food choices, glucocorticoids, insulin and abdominal obesity

    Mol. Cell. Endocrinol.

    (2009)
  • S. Benson

    Effects of obesity on neuroendocrine, cardiovascular, and immune cell responses to acute psychological stress in premenopausal women

    Psychoneuroendocrinol.

    (2009)
  • K.A. Clark

    Systemic administration of leptin decreases plasma corticosterone levels: role of hypothalamic norepinephrine

    Brain Res.

    (2008)
  • S. Hinuma

    A prolactin-releasing peptide in the brain

    Nature

    (1998)
  • D.A. Bechtold et al.

    The role of RFamide peptides in feeding

    J. Endocrinol.

    (2007)
  • S.H. Lin

    Prolactin-releasing peptide

    Results Probl. Cell Differ.

    (2008)
  • C.J. Langmead

    Characterization of the binding of [(125)I]-human prolactin releasing peptide (PrRP) to GPR10, a novel G protein coupled receptor

    Br. J. Pharmacol.

    (2000)
  • M. Engstrom

    Prolactin-releasing peptide has high affinity and efficacy at neuropeptide FF2 receptors

    J. Pharmacol. Exp. Ther.

    (2003)
  • A. Quelven

    Comparison of pharmacological activities of neuropeptide FF1 and neuropeptide FF2 receptor agonists

    Eur. J. Pharmacol.

    (2005)
  • L. Ma

    Prolactin-releasing peptide effects in the rat brain are mediated through the Neuropeptide FF receptor

    Eur. J. Neurosci.

    (2009)
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