Journal of Ornithology

, Volume 148, Supplement 2, pp 515–520 | Cite as

Discovery of gonadotropin-inhibitory hormone in a domesticated bird, its mode of action and functional significance

  • Kazuyoshi Tsutsui
  • Takayoshi Ubuka
  • Hong Yin
  • Tomohiro Osugi
  • Kazuyoshi Ukena
  • George E. Bentley
  • Peter J. Sharp
  • John C. Wingfield
Review

Abstract

Neuropeptide control of gonadotropin secretion at the level of the anterior pituitary gland is primarily through the stimulatory action of the hypothalamic decapeptide gonadotropin-releasing hormone (GnRH) in vertebrates. Until recently, no neuropeptide that directly inhibits gonadotropin secretion had been identified. In 2000, we discovered a novel hypothalamic dodecapeptide that directly inhibits gonadotropin release in quail and termed it gonadotropin-inhibitory hormone (GnIH). A gonadotropin inhibitory system is an intriguing concept and provides us with an unprecedented opportunity to study the regulation of avian reproduction from an entirely novel standpoint. To elucidate the mode of action of GnIH, we then identified a novel G protein-coupled receptor for GnIH in quail. The receptor possessed seven transmembrane domains and specifically bound to GnIH in a concentration-dependent manner. The GnIH receptor was found to be expressed in the pituitary and several brain regions including the hypothalamus. These results indicate that GnIH acts directly on the pituitary via GnIH receptor to inhibit gonadotropin release. GnIH may also act on the hypothalamus to inhibit GnRH release, because GnIH fibers were observed to contact GnRH cell bodies. To demonstrate the functional significance of GnIH and its potential role as a key neuropeptide involved in avian reproduction, we further investigated the action of GnIH on gonadal development and maintenance in quail. Chronic treatment with GnIH inhibited photoinduced testicular development and maintenance by decreasing gonadotropin synthesis and release. Melatonin is a key factor involved in GnIH neural function. Quail GnIH neurons were found to contain melatonin receptor and melatonin stimulated expression of GnIH mRNA and mature GnIH peptide in a dose-dependent manner. It is concluded that GnIH is capable of transducing photoperiodic information via changes in the melatonin signal and of influencing the reproductive axes of birds.

Keywords

Gonadotropins Gonadotropin-inhibitory hormone (GnIH) Gonadotropin-releasing hormone (GnRH) Melatonin Hypothalamus Pituitary Reproduction 

Notes

Acknowledgments

This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture, Japan (15207007, 16086206 and 18107002) and NIH, USA (RO1 MH065974).

References

  1. Bentley GE (2001) Unraveling the enigma: the role of melatonin in seasonal processes in birds. Microsc Res Tech 53:63–71PubMedCrossRefGoogle Scholar
  2. Bentley GE, Ball GF (2000) Photoperiod-dependent and -independent regulation of melatonin receptors in the forebrain of songbirds. J Neuroendocrinol 12:745–752Google Scholar
  3. Bentley GE, Van’t Hof TJ, Ball GF (1999) Seasonal neuroplasticity in the songbird telencephalon: a role for melatonin. Proc Natl Acad Sci USA 13:4674–4679CrossRefGoogle Scholar
  4. Bentley GE, Perfito N, Ukena K, Tsutsui K, Wingfield JC (2003) Gonadotropin-inhibitory peptide in song sparrows (Melospiza melodia) in different reproductive conditions, and in house sparrows (Passer domesticus) relative to chicken-gonadotropin-releasing hormone. J Neuroendocrinol 15:794–802PubMedCrossRefGoogle Scholar
  5. Bentley GE, Jensen JP, Kaur GJ, Wacker DW, Tsutsui K, Wingfield JC (2006) Rapid inhibition of female sexual behavior by gonadotropin-inhibitory hormone (GnIH). Horm Behav 49:550–555PubMedCrossRefGoogle Scholar
  6. Burgus R, Butcher M, Amoss M, Ling N, Monahan M, Rivier J, Fellows R, Blackwell R, Vale W, Guillemin R (1972) Primary structure of the ovine hypothalamic luteinizing hormone-releasing factor (LRF). Proc Natl Acad Sci USA 69:278–282PubMedCrossRefGoogle Scholar
  7. Ciccone NA, Dunn IC, Boswell T, Tsutsui K, Ubuka T, Ukena K, Sharp PJ (2004) Gonadotrophin inhibitory hormone depresses gonadotrophin α and follicle-stimulating hormone β subunit expression in the pituitary of the domestic chicken. J Neuroendocrinol 16:999–1006Google Scholar
  8. Cockrem JF, Follett BK (1985) Circadian rhythm of melatonin in the pineal gland of the Japanese quail (Coturnix coturnix japonica). J Endocrinol 107:317–324PubMedGoogle Scholar
  9. Dockray GJ, Dimaline R (1985) FMRFamide- and gastrin/CCK-like peptides in birds. Peptides 3:333–337CrossRefGoogle Scholar
  10. Dockray GJ, Reeve JR Jr, Shively J, Gayton RJ, Barnard CS (1983) A novel active pentapeptide from chicken brain identified by antibodies to FMRFamide. Nature 305:328–330PubMedCrossRefGoogle Scholar
  11. Guyomarc’h C, Lumineau S, Vivien-Roels B, Richard J, Deregnaucourt S (2001) Effect of melatonin supplementation on the sexual development in European quail (Coturnix coturnix). Behav Processes 53:121–130PubMedCrossRefGoogle Scholar
  12. Juss TS, Meddle SL, Servant RS, King VM (1993) Melatonin and photoperiodic time measurement in Japanese quail (Coturnix coturnix japonica). Proc R Soc Lond B Biol Sci 254:21–28CrossRefGoogle Scholar
  13. Kauffman AS, Rissman EF (2004) A critical role for the evolutionarily conserved gonadotropin-releasing hormone II: mediation of energy status and female sexual behavior. Endocrinology 145:3639–3646PubMedCrossRefGoogle Scholar
  14. King JA, Millar RP (1982a) Structure of chicken hypothalamic luteinizing hormone-releasing hormone. I. Structural determination on partially purified material. J Biol Chem 257:10722–10728PubMedGoogle Scholar
  15. King JA, Millar RP (1982b) Structure of chicken hypothalamic luteinizing hormone-releasing hormone. II. Isolation and characterization. J Biol Chem 257:10729–10732PubMedGoogle Scholar
  16. Kriegsfeld LJ, Mei DF, Bentley GE, Ubuka T, Mason AA, Inoue K, Ukena K, Tsutsui K, Silver R (2006) Identification and characterization of a gonadotropin-inhibitory system in the brain of mammals. Proc Natl Acad Sci USA 103:2410–2415PubMedCrossRefGoogle Scholar
  17. Li Q, Tamarkin L, Levantine P, Ottinger MA (1994) Estradiol and androgen modulate chicken luteinizing hormone-releasing hormone-I release in vitro. Biol Reprod 51:896–903PubMedCrossRefGoogle Scholar
  18. Maney DL, Richardson RD, Wingfield JC (1997) Central administration of chicken gonadotropin-releasing hormone-II enhances courtship behavior in a female sparrow. Horm Behav 32:11–18PubMedCrossRefGoogle Scholar
  19. Matsuo H, Baba Y, Nair RMG, Arimura A, Schally AV (1971) Structure of the porcine LH- and FSH-releasing hormone. I. The proposed amino acid sequence. Biochem Biophys Res Commun 43:1334–1339PubMedCrossRefGoogle Scholar
  20. Miyamoto K, Hasegawa Y, Minegishi T, Nomura M, Takahashi Y, Igarashi M, Kangawa K, Matsuo H (1982) Isolation and characterization of chicken hypothalamic luteinizing hormone-releasing hormone. Biochem Biophys Res Commun 107:820–827PubMedCrossRefGoogle Scholar
  21. Miyamoto K, Hasegawa Y, Nomura M, Igarashi M, Kangawa K, Matsuo H (1984) Identification of the second gonadotrophin-releasing hormone in chicken hypothalamus: evidence that gonadotrophin secretion is probably controlled by two distinct gonadotropin-releasing hormones in avian species. Proc Natl Acad Sci USA 81:3874–3878PubMedCrossRefGoogle Scholar
  22. Ohta M, Kadota C, Konishi H (1989) A role of melatonin in the initial stage of photoperiodism in the Japanese quail. Biol Reprod 40:935–941PubMedCrossRefGoogle Scholar
  23. Osugi T, Ukena K, Bentley GE, O’Brien S, Moore IT, Wingfield JC, Tsutsui K (2004) Gonadotropin-inhibitory hormone in Gambel’s white-crowned sparrows: cDNA identification, transcript localization and functional effects in laboratory and field experiments. J Endocrinol 182:33–42PubMedCrossRefGoogle Scholar
  24. Price DA, Greenberg MJ (1977) Structure of a molluscan cardioexcitatory neuropeptide. Science 197:670–671PubMedCrossRefGoogle Scholar
  25. Raffa RB (1988) The action of FMRFamide (Phe-Met-Arg-Phe-NH2) and related peptides on mammals. Peptides 9:915–922PubMedCrossRefGoogle Scholar
  26. Rastogi RK, D’Aniello B, Pinelli C, Fiorentino M, Di Fiore MM, Di Meglio M, Iela L (2001) FMRFamide in the amphibian brain: a comprehensive survey. Microsc Res Tech 54:158–172PubMedCrossRefGoogle Scholar
  27. Rozenboim I, Aharony T, Yahav S (2002) The effect of melatonin administration on circulating plasma luteinizing hormone concentration in castrated White Leghorn roosters. Poult Sci 81:1354–1359PubMedGoogle Scholar
  28. Satake H, Hisada M, Kawada T, Minakata H, Ukena K, Tsutsui K (2001) Characterization of a cDNA encoding a novel avian hypothalamic neuropeptide exerting an inhibitory effect on gonadotropin release. Biochem J 354:379–385PubMedCrossRefGoogle Scholar
  29. Sharp PJ, Talbot RT, Main GM, Dunn IC, Fraser HM, Huskisson NS (1990) Physiological roles of chicken LHRH-I and -II in the control of gonadotrophin release in the domestic chicken. J Endocrinol 124:291–299PubMedCrossRefGoogle Scholar
  30. Sherwood N, Eiden L, Brownstein M, Spiess J, Rivier J, Vale W (1983) Characterization of a teleost gonadotrophin-releasing hormone. Proc Natl Acad Sci USA 80:2794–2798PubMedCrossRefGoogle Scholar
  31. Sherwood NM, Sower SA, Marshak DR, Fraser BA, Brownstein MJ (1986) Primary structure of gonadotrophin-releasing hormone from lamprey brain. J Biol Chem 261:4812–4819PubMedGoogle Scholar
  32. Sherwood NM, Wingfield JC, Ball GF, Dufty AM (1988) Identity of gonadotropin-releasing hormone in passerine birds: comparison of GnRH in song sparrow (Melospiza melodia) and starling (Sturnus vulgaris) with five vertebrate GnRHs. Gen Comp Endocrinol 69:341–351PubMedCrossRefGoogle Scholar
  33. Sun Y-M, Dunn IC, Baines E, Talbot RT, Illing N, Millar RP, Sharp PJ (2001) Distribution and regulation by oestrogen of fully processed and variant transcripts of gonadotrophin releasing hormones I and gonadotrophin releasing hormone receptor mRNAs in the male chicken. J Neuroendocrinol 13:37–49PubMedCrossRefGoogle Scholar
  34. Tachibana T, Sato M, Takahashi H, Ukena K, Tsutsui K, Furuse M (2005) Gonadotropin-inhibiting hormone stimulates feeding behavior in chicks. Brain Res 1050:94–100PubMedCrossRefGoogle Scholar
  35. Tsutsui K, Ukena K (2006) Review: hypothalamic LPXRF-amide peptides in vertebrates: identification, localization and hypophysiotropic activity. Peptides 27:1121–1129PubMedCrossRefGoogle Scholar
  36. Tsutsui K, Saigoh E, Ukena K, Teranishi H, Fujisawa Y, Kikuchi M, Ishii S, Sharp PJ (2000) A novel avian hypothalamic peptide inhibiting gonadotropin release. Biochem Biophys Res Commun 275:661–667PubMedCrossRefGoogle Scholar
  37. Tsutsui K, Bentley GE, Ciccone N (2005) Structure, action and functional significance of GnIH. In: Dawson A, Sharp PJ (eds) Functional avian endocrinology. Narosa, New Delhi, pp 73–82Google Scholar
  38. Tsutsui K, Ubuka T, Yin H, Osugi T, Ukena K, Bentley GE, Ciccone N, Inoue K, Chowdhury VS, Sharp PJ, Wingfield JC (2006) Mode of action and functional significance of avian gonadotropin-inhibitory hormone (GnIH): a review. J Exp Zool 305A:801–806CrossRefGoogle Scholar
  39. Ubuka T, Ueno M, Ukena K, Tsutsui K (2003) Developmental changes in gonadotropin-inhibitory hormone in the Japanese quail (Coturnix japonica) hypothalamo–hypophysial system. J Endocrinol 178:311–318PubMedCrossRefGoogle Scholar
  40. Ubuka T, Bentley GE, Ukena K, Wingfield JC, Tsutsui K (2005) Melatonin induces the expression of gonadotropin-inhibitory hormone in the avian brain. Proc Natl Acad Sci USA 102:3052–3057 (Nature Reviews Highlight)PubMedCrossRefGoogle Scholar
  41. Ubuka T, Ukena K, Sharp PJ, Bentley GE, Tsutsui K (2006) Gonadotropin-inhibitory hormone inhibits gonadal development and maintenance by decreasing gonadotropin synthesis and release in male quail. Endocrinology 147:1187–1194PubMedCrossRefGoogle Scholar
  42. Ukena K, Ubuka T, Tsutsui K (2003) Distribution of a novel avian gonadotropin-inhibitory hormone in the quail brain. Cell Tissue Res 312:73–79PubMedGoogle Scholar
  43. Wilson FE (1991) Neither retinal nor pineal photoreceptors mediate photoperiodic control of seasonal reproduction in American tree sparrows (Spizella arborea). J Exp Zool 259:117–127CrossRefGoogle Scholar
  44. Yin H, Ukena K, Ubuka T, Tsutsui K (2005) A novel G protein-coupled receptor for gonadotropin-inhibitory hormone in the Japanese quail (Coturnix japonica): identification, expression and binding activity. J Endocrinol 184:257–266PubMedCrossRefGoogle Scholar

Copyright information

© Dt. Ornithologen-Gesellschaft e.V. 2007

Authors and Affiliations

  • Kazuyoshi Tsutsui
    • 1
  • Takayoshi Ubuka
    • 2
  • Hong Yin
    • 1
  • Tomohiro Osugi
    • 1
    • 3
  • Kazuyoshi Ukena
    • 3
  • George E. Bentley
    • 2
  • Peter J. Sharp
    • 4
  • John C. Wingfield
    • 5
  1. 1.Laboratory of Integrative Brain Sciences, Department of Biology, Faculty of Education and Integrated Arts and SciencesWaseda UniversityTokyoJapan
  2. 2.Department of Integrative BiologyUniversity of CaliforniaBerkeleyUSA
  3. 3.Laboratory of Brain Science, Faculty of Integrated Arts and SciencesHiroshima UniversityHigashi-HiroshimaJapan
  4. 4.Division of Genetics and GenomicsRoslin InstituteMidlothianUK
  5. 5.Department of BiologyUniversity of WashingtonSeattleUSA

Personalised recommendations