Mitochondrial dysfunction in GnRH neurons impaired GnRH production
Autor: | Subrata Kumar Shil, Yoshiteru Kagawa, Yukio Katori, Shuhei Kobayashi, Ryo Zama, Hirofumi Miyazaki, Takaaki Abe, Chitose Suzuki, Ken Hayasaka, Yuta Kobayashi, Yuji Owada, Banlanjo Abdulaziz Umaru |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
endocrine system medicine.medical_specialty Hypothalamus Biophysics Stimulation Mitochondrion CREB Biochemistry Cell Line Gonadotropin-Releasing Hormone Mice 03 medical and health sciences 0302 clinical medicine Kisspeptin Internal medicine medicine Animals Protein Precursors Molecular Biology Neurons GnRH Neuron Electron Transport Complex I biology NDUFS4 Cell Biology Mitochondria 030104 developmental biology Endocrinology Gene Expression Regulation nervous system 030220 oncology & carcinogenesis Median eminence biology.protein hormones hormone substitutes and hormone antagonists |
Zdroj: | Biochemical and Biophysical Research Communications. 530:329-335 |
ISSN: | 0006-291X |
Popis: | 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. |
Databáze: | OpenAIRE |
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