Mitochondrial dysfunction in GnRH neurons impaired GnRH production

Yoshiteru Kagawa, Banlanjo Abdulaziz Umaru, Subrata Kumar Shil, Ken Hayasaka, Ryo Zama, Yuta Kobayashi, Hirofumi Miyazaki, Shuhei Kobayashi, Chitose Suzuki, Yukio Katori, Takaaki Abe, Yuji Owada

Research output: Contribution to journalArticle

Abstract

The onset establishment and maintenance of gonadotropin-releasing hormone (GnRH) secretion is an important phenomenon regulating pubertal development and reproduction. GnRH neurons as well as other neurons in the hypothalamus have high-energy demands and require a constant energy supply from their mitochondria machinery to maintain active functioning. However, the involvement of mitochondrial function in GnRH neurons is still unclear. In this study, we examined the role of NADH Dehydrogenase (Ubiquinone) Fe–S protein 4 (Ndufs4), a member of the mitochondrial complex 1, on GnRH neurons using Ndufs4-KO mice and Ndufs4-KO GT1-7 cells. Ndufs4 was highly expressed in GnRH neurons in the medial preoptic area (MPOA) and NPY/AgRP and POMC neurons in the arcuate (ARC) nucleus in WT mice. Conversely, there was a significant decrease in GnRH expression in MPOA and median eminence of Ndufs4-KO mice, followed by impaired peripheral endocrine system. In Ndufs4-KO GT1-7 cells, Gnrh1 expression was significantly decreased with or without stimulation with either kisspeptin or NGF, whereas, stimulation significantly increased Gnrh1 expression in control cells. In contrast, there was no difference in cell signaling activity including ERK and CREB as well as the expression of GPR54, TrkA and p75NTR, suggesting that Ndufs4 is involved in the transcriptional regulation system for GnRH production. These findings may be useful in understanding the mitochondrial function in GnRH neuron.

Original languageEnglish
Pages (from-to)329-335
Number of pages7
JournalBiochemical and biophysical research communications
Volume530
Issue number1
DOIs
Publication statusPublished - 2020 Sep 10

Keywords

  • GnRH
  • GnRH neuron
  • Mitochondria
  • Ndufs4
  • Transcription

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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