Download PDF
Semin Reprod Med 2019; 37(04): 191-196
DOI: 10.1055/s-0039-3400964
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Phoenixin and Its Role in Reproductive Hormone Release

Sophie A. Clarke
1   Section of Endocrinology and Investigative Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom
,
Waljit S. Dhillo
1   Section of Endocrinology and Investigative Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom
› Author Affiliations
Further Information

Publication History

Publication Date:
23 January 2020 (online)

    Permissions and Reprints

Abstract

Phoenixin is novel neuropeptide, recently identified following the description of a peptide sequence highly conserved across several animal species, including humans, cows, and pigs. Expressed both centrally in the hypothalamus and arcuate nucleus and peripherally in cardiac and gastrointestinal tissue, it appears to modulate reproductive hormone secretion in a gonadotrophin-releasing hormone–dependent manner and may also influence anxiety and memory. While there remains much to be described regarding its signaling, this review assesses the currently available literature in both animal and human studies to summarize our understanding of the physiological role of this novel neuropeptide, and its function in reproductive hormone release.

Keywords

phoenixin - reproduction - GnRH - kisspeptin
 

  • References

  • 1 Yosten GL, Lyu RM, Hsueh AJ. , et al. A novel reproductive peptide, phoenixin. J Neuroendocrinol 2013; 25 (02) 206-215
    CrossrefPubMedGoogle Scholar
  • 2 Samson WK, Zhang JV, Avsian-Kretchmer O. , et al. Neuronostatin encoded by the somatostatin gene regulates neuronal, cardiovascular, and metabolic functions. J Biol Chem 2008; 283 (46) 31949-31959
    CrossrefPubMedGoogle Scholar
  • 3 Gasparini S, Stein LM, Loewen SP. , et al. Novel regulator of vasopressin secretion: phoenixin. Am J Physiol Regul Integr Comp Physiol 2018; 314 (04) R623-R628
    CrossrefPubMedGoogle Scholar
  • 4 Mcilwraith EK, Belsham DD. Phoenixin: uncovering its receptor, signaling and functions. Acta Pharmacol Sin 2018; 39 (05) 774-778
    CrossrefPubMedGoogle Scholar
  • 5 Prinz P, Scharner S, Friedrich T. , et al. Central and peripheral expression sites of phoenixin-14 immunoreactivity in rats. Biochem Biophys Res Commun 2017; 493 (01) 195-201
    CrossrefPubMedGoogle Scholar
  • 6 Suszka-Świtek A, Pałasz A, Filipczyk Ł. , et al. The GnRH analogues affect novel neuropeptide SMIM20/phoenixin and GPR173 receptor expressions in the female rat hypothalamic-pituitary-gonadal (HPG) axis. Clin Exp Pharmacol Physiol 2019; 46 (04) 350-359
    CrossrefPubMedGoogle Scholar
  • 7 Stein LM, Tullock CW, Mathews SK. , et al. Hypothalamic action of phoenixin to control reproductive hormone secretion in females: importance of the orphan G protein-coupled receptor Gpr173. Am J Physiol Regul Integr Comp Physiol 2016; 311 (03) R489-R496
    CrossrefPubMedGoogle Scholar
  • 8 Matsumoto M, Saito T, Takasaki J. , et al. An evolutionarily conserved G-protein coupled receptor family, SREB, expressed in the central nervous system. Biochem Biophys Res Commun 2000; 272 (02) 576-582
    CrossrefPubMedGoogle Scholar
  • 9 Treen AK, Luo V, Belsham DD. Phoenixin activates immortalized GnRH and kisspeptin neurons through the novel receptor GPR173. Mol Endocrinol 2016; 30 (08) 872-888
    CrossrefPubMedGoogle Scholar
  • 10 Ullah K, Ur Rahman T, Wu DD. , et al. Phoenixin-14 concentrations are increased in association with luteinizing hormone and nesfatin-1 concentrations in women with polycystic ovary syndrome. Clin Chim Acta 2017; 471 (January): 243-247
    CrossrefPubMedGoogle Scholar
  • 11 Nguyen XP, Nakamura T, Osuka S. , et al. Effect of the neuropeptide phoenixin and its receptor GPR173 during folliculogenesis. Reproduction 2019 Doi: 10.1530/REP-19-0025. [Epub ahead of print]
    PubMedGoogle Scholar
  • 12 Dhillo WS, Chaudhri OB, Patterson M. , et al. Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males. J Clin Endocrinol Metab 2005; 90 (12) 6609-6615
    CrossrefPubMedGoogle Scholar
  • 13 Clarke SA, Dhillo WS. Kisspeptin across the human lifespan: evidence from animal studies and beyond. J Endocrinol 2016; 229 (03) R83-R98
    CrossrefPubMedGoogle Scholar
  • 14 Seminara SB, Messager S, Chatzidaki EE. , et al. The GPR54 gene as a regulator of puberty. N Engl J Med 2003; 349 (17) 1614-1627
    CrossrefPubMedGoogle Scholar
  • 15 de Roux N, Genin E, Carel J-C, Matsuda F, Chaussain J-L, Milgrom E. Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. Proc Natl Acad Sci U S A 2003; 100 (19) 10972-10976
    CrossrefPubMedGoogle Scholar
  • 16 Gottsch ML, Cunningham MJ, Smith JT. , et al. A role for kisspeptins in the regulation of gonadotropin secretion in the mouse. Endocrinology 2004; 145 (09) 4073-4077
    CrossrefPubMedGoogle Scholar
  • 17 Pałasz A, Janas-Kozik M, Borrow A, Arias-Carrión O, Worthington JJ. The potential role of the novel hypothalamic neuropeptides nesfatin-1, phoenixin, spexin and kisspeptin in the pathogenesis of anxiety and anorexia nervosa. Neurochem Int 2018; 113: 120-136
    CrossrefPubMedGoogle Scholar
  • 18 Stengel A, Taché Y. Nesfatin-1--role as possible new potent regulator of food intake. Regul Pept 2010; 163 (1-3): 18-23
    CrossrefPubMedGoogle Scholar
  • 19 Wernecke K, Lamprecht I, Jöhren O, Lehnert H, Schulz C. Nesfatin-1 increases energy expenditure and reduces food intake in rats. Obesity (Silver Spring) 2014; 22 (07) 1662-1668
    CrossrefPubMedGoogle Scholar
  • 20 Stengel A, Taché Y. Role of NUCB2/Nesfatin-1 in the hypothalamic control of energy homeostasis. Horm Metab Res 2013; 45 (13) 975-979
    Article in Thieme ConnectPubMedGoogle Scholar
  • 21 García-Galiano D, Navarro VM, Roa J. , et al. The anorexigenic neuropeptide, nesfatin-1, is indispensable for normal puberty onset in the female rat. J Neurosci 2010; 30 (23) 7783-7792
    CrossrefPubMedGoogle Scholar
  • 22 Schalla M, Prinz P, Friedrich T. , et al. Phoenixin-14 injected intracerebroventricularly but not intraperitoneally stimulates food intake in rats. Peptides 2017; 96 (May): 53-60
    CrossrefPubMedGoogle Scholar
  • 23 Ademoglu EN, Gorar S, Carlıoglu A. , et al. Plasma nesfatin-1 levels are increased in patients with polycystic ovary syndrome. J Endocrinol Invest 2014; 37 (08) 715-719
    CrossrefPubMedGoogle Scholar
  • 24 Deniz R, Gurates B, Aydin S. , et al. Nesfatin-1 and other hormone alterations in polycystic ovary syndrome. Endocrine 2012; 42 (03) 694-699
    CrossrefPubMedGoogle Scholar
  • 25 Telegdy G, Tanaka M, Schally AV. Effects of the LHRH antagonist Cetrorelix on the brain function in mice. Neuropeptides 2009; 43 (03) 229-234
    CrossrefPubMedGoogle Scholar
  • 26 Telegdy G, Adamik A, Tanaka M, Schally AV. Effects of the LHRH antagonist Cetrorelix on affective and cognitive functions in rats. Regul Pept 2010; 159 (1-3): 142-147
    CrossrefPubMedGoogle Scholar
  • 27 Umathe SN, Bhutada PS, Jain NS, Shukla NR, Mundhada YR, Dixit PV. Gonadotropin-releasing hormone agonist blocks anxiogenic-like and depressant-like effect of corticotrophin-releasing hormone in mice. Neuropeptides 2008; 42 (04) 399-410
    CrossrefPubMedGoogle Scholar
  • 28 Jiang JH, He Z, Peng YL. , et al. Effects of phoenixin-14 on anxiolytic-like behavior in mice. Behav Brain Res 2015; 286: 39-48
    CrossrefPubMedGoogle Scholar
  • 29 Hofmann T, Weibert E, Ahnis A. , et al. Phoenixin is negatively associated with anxiety in obese men. Peptides 2017; 88: 32-36
    CrossrefPubMedGoogle Scholar
  • 30 Jiang JH, He Z, Peng YL. , et al. Phoenixin-14 enhances memory and mitigates memory impairment induced by Aβ1-42 and scopolamine in mice. Brain Res 2015; 1629: 298-308
    CrossrefPubMedGoogle Scholar
  • 31 Yuruyen M, Gultekin G, Batun GC. , et al. Does plasma phoenixin level associate with cognition? Comparison between subjective memory complaint, mild cognitive impairment, and mild Alzheimer's disease. Int Psychogeriatr 2017; 29 (09) 1-8
    PubMedGoogle Scholar
  • 32 Rocca C, Scavello F, Granieri MC. , et al. Phoenixin-14: detection and novel physiological implications in cardiac modulation and cardioprotection. Cell Mol Life Sci 2018; 75 (04) 743-756
    CrossrefPubMedGoogle Scholar
  • 33 Cowan A, Lyu RM, Chen YH, Dun SL, Chang JK, Dun NJ. Phoenixin: A candidate pruritogen in the mouse. Neuroscience 2015; 310: 541-548
    CrossrefPubMedGoogle Scholar