Melatonin induces the expression of gonadotropin-inhibitory hormone in the avian brain

Takayoshi Ubuka, George E. Bentley, Kazuyoshi Ukena, John C. Wingfield, Kazuyoshi Tsutsui*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

273 Citations (Scopus)


We recently identified a novel hypothalamic neuropeptide inhibiting gonadotropin release in quail and termed it gonadotropin-inhibitory hormone (GnIH). Cell bodies and terminals containing the dodecapeptide GnIH are localized in the paraventricular nucleus (PVN) and median eminence, respectively. To understand the physiological role of GnIH, we investigated the mechanisms that regulate GnIH expression. In this study, we show that melatonin originating from the pineal gland and eyes induces GnIH expression in the quail brain. Pinealectomy (Px) combined with orbital enucleation (Ex) (Px plus Ex) decreased the expression of GnIH precursor mRNA and content of mature GnIH peptide in the diencephalon, which includes the PVN and median eminence. Melatonin administration to Px plus Ex birds caused a dose-dependent increase in expression of GnIH precursor mRNA and production of mature peptide. The expression of GnIH was photoperiodically controlled and increased under short-day photoperiods, when the duration of melatonin secretion increases. To identify the mode of melatonin action on GnIH induction, we investigated the expression of Mel1c, a melatonin receptor subtype, in GnIH neurons. In situ hybridization of Mel1c mRNA combined with immunocytochemistry for GnIH revealed that Mel1c mRNA was expressed in GnIH-immunoreactive neurons in the PVN. Melatonin receptor autoradiography further revealed specific binding of melatonin in the PVN. These results indicate that melatonin is a key factor for GnIH induction. Melatonin appears to act directly on GnIH neurons through its receptor to induce GnIH expression. This is the first demonstration, to our knowledge, of a direct action of melatonin on neuropeptide induction in any vertebrate class.

Original languageEnglish
Pages (from-to)3052-3057
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number8
Publication statusPublished - 2005 Feb 22
Externally publishedYes


  • Melatonin receptor
  • Photoperiod
  • Reproduction

ASJC Scopus subject areas

  • Genetics
  • General


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