Skip to main content
Log in

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

  • Review
  • Published:
Journal of Ornithology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  • Bentley GE (2001) Unraveling the enigma: the role of melatonin in seasonal processes in birds. Microsc Res Tech 53:63–71

    Article  PubMed  CAS  Google Scholar 

  • Bentley GE, Ball GF (2000) Photoperiod-dependent and -independent regulation of melatonin receptors in the forebrain of songbirds. J Neuroendocrinol 12:745–752

    Google Scholar 

  • Bentley GE, Van’t Hof TJ, Ball GF (1999) Seasonal neuroplasticity in the songbird telencephalon: a role for melatonin. Proc Natl Acad Sci USA 13:4674–4679

    Article  Google Scholar 

  • 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 15:794–802

    Article  PubMed  CAS  Google Scholar 

  • 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 49:550–555

    Article  PubMed  CAS  Google Scholar 

  • 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 69:278–282

    Article  PubMed  CAS  Google Scholar 

  • 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 16:999–1006

    Google Scholar 

  • Cockrem JF, Follett BK (1985) Circadian rhythm of melatonin in the pineal gland of the Japanese quail (Coturnix coturnix japonica). J Endocrinol 107:317–324

    PubMed  CAS  Google Scholar 

  • Dockray GJ, Dimaline R (1985) FMRFamide- and gastrin/CCK-like peptides in birds. Peptides 3:333–337

    Article  Google Scholar 

  • 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 305:328–330

    Article  PubMed  CAS  Google Scholar 

  • 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 53:121–130

    Article  PubMed  Google Scholar 

  • 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 254:21–28

    Article  CAS  Google Scholar 

  • 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 145:3639–3646

    Article  PubMed  CAS  Google Scholar 

  • King JA, Millar RP (1982a) Structure of chicken hypothalamic luteinizing hormone-releasing hormone. I. Structural determination on partially purified material. J Biol Chem 257:10722–10728

    PubMed  CAS  Google Scholar 

  • King JA, Millar RP (1982b) Structure of chicken hypothalamic luteinizing hormone-releasing hormone. II. Isolation and characterization. J Biol Chem 257:10729–10732

    PubMed  CAS  Google Scholar 

  • 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 103:2410–2415

    Article  PubMed  CAS  Google Scholar 

  • Li Q, Tamarkin L, Levantine P, Ottinger MA (1994) Estradiol and androgen modulate chicken luteinizing hormone-releasing hormone-I release in vitro. Biol Reprod 51:896–903

    Article  PubMed  CAS  Google Scholar 

  • Maney DL, Richardson RD, Wingfield JC (1997) Central administration of chicken gonadotropin-releasing hormone-II enhances courtship behavior in a female sparrow. Horm Behav 32:11–18

    Article  PubMed  CAS  Google Scholar 

  • 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 43:1334–1339

    Article  PubMed  CAS  Google Scholar 

  • 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 107:820–827

    Article  PubMed  CAS  Google Scholar 

  • 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 81:3874–3878

    Article  PubMed  CAS  Google Scholar 

  • Ohta M, Kadota C, Konishi H (1989) A role of melatonin in the initial stage of photoperiodism in the Japanese quail. Biol Reprod 40:935–941

    Article  PubMed  CAS  Google Scholar 

  • 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 182:33–42

    Article  PubMed  CAS  Google Scholar 

  • Price DA, Greenberg MJ (1977) Structure of a molluscan cardioexcitatory neuropeptide. Science 197:670–671

    Article  PubMed  CAS  Google Scholar 

  • Raffa RB (1988) The action of FMRFamide (Phe-Met-Arg-Phe-NH2) and related peptides on mammals. Peptides 9:915–922

    Article  PubMed  CAS  Google Scholar 

  • 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 54:158–172

    Article  PubMed  CAS  Google Scholar 

  • 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 81:1354–1359

    PubMed  CAS  Google Scholar 

  • 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 354:379–385

    Article  PubMed  CAS  Google Scholar 

  • 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 124:291–299

    Article  PubMed  CAS  Google Scholar 

  • 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 80:2794–2798

    Article  PubMed  CAS  Google Scholar 

  • Sherwood NM, Sower SA, Marshak DR, Fraser BA, Brownstein MJ (1986) Primary structure of gonadotrophin-releasing hormone from lamprey brain. J Biol Chem 261:4812–4819

    PubMed  CAS  Google Scholar 

  • 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 69:341–351

    Article  PubMed  CAS  Google Scholar 

  • 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 13:37–49

    Article  PubMed  CAS  Google Scholar 

  • Tachibana T, Sato M, Takahashi H, Ukena K, Tsutsui K, Furuse M (2005) Gonadotropin-inhibiting hormone stimulates feeding behavior in chicks. Brain Res 1050:94–100

    Article  PubMed  CAS  Google Scholar 

  • Tsutsui K, Ukena K (2006) Review: hypothalamic LPXRF-amide peptides in vertebrates: identification, localization and hypophysiotropic activity. Peptides 27:1121–1129

    Article  PubMed  CAS  Google Scholar 

  • 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 275:661–667

    Article  PubMed  CAS  Google Scholar 

  • 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 73–82

  • 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:801–806

    Article  CAS  Google Scholar 

  • 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 178:311–318

    Article  PubMed  CAS  Google Scholar 

  • 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)

    Article  PubMed  CAS  Google Scholar 

  • 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 147:1187–1194

    Article  PubMed  CAS  Google Scholar 

  • Ukena K, Ubuka T, Tsutsui K (2003) Distribution of a novel avian gonadotropin-inhibitory hormone in the quail brain. Cell Tissue Res 312:73–79

    PubMed  CAS  Google Scholar 

  • Wilson FE (1991) Neither retinal nor pineal photoreceptors mediate photoperiodic control of seasonal reproduction in American tree sparrows (Spizella arborea). J Exp Zool 259:117–127

    Article  Google Scholar 

  • 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 184:257–266

    Article  PubMed  CAS  Google Scholar 

Download references

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).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kazuyoshi Tsutsui.

Additional information

Communicated by F. Bairlein.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tsutsui, K., Ubuka, T., Yin, H. et al. Discovery of gonadotropin-inhibitory hormone in a domesticated bird, its mode of action and functional significance. J Ornithol 148 (Suppl 2), 515–520 (2007). https://doi.org/10.1007/s10336-007-0225-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10336-007-0225-2

Keywords

Navigation