Involvement of α-klotho in growth hormone (GH) signaling

DOI 機関リポジトリ Web Site 参考文献49件
  • Koike Megumi
    Department of Applied Nutrition, Institute of Biomedical Sciences, Tokushima University Graduate School
  • Sato Tetsuhiko
    General Medicine, Nagoya Daini Red Cross Hospital
  • Shiozaki Yuji
    Department of Applied Nutrition, Institute of Biomedical Sciences, Tokushima University Graduate School
  • Komiya Aoi
    Department of Applied Nutrition, Institute of Biomedical Sciences, Tokushima University Graduate School
  • Miura Mizuki
    Department of Applied Nutrition, Institute of Biomedical Sciences, Tokushima University Graduate School
  • Higashi Ayami
    Department of Applied Nutrition, Institute of Biomedical Sciences, Tokushima University Graduate School
  • Ishikawa Akane
    Department of Applied Nutrition, Institute of Biomedical Sciences, Tokushima University Graduate School
  • Takayanagi Kaori
    Department of Applied Nutrition, Institute of Biomedical Sciences, Tokushima University Graduate School
  • Uga Minori
    Department of Applied Nutrition, Institute of Biomedical Sciences, Tokushima University Graduate School
  • Miyamoto Ken-ichi
    Department of Applied Nutrition, Institute of Biomedical Sciences, Tokushima University Graduate School Graduate School of Agriculture, Ryukoku University
  • Segawa Hiroko
    Department of Applied Nutrition, Institute of Biomedical Sciences, Tokushima University Graduate School

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<p>Growth hormone (GH) exerts multiple effects on different organs directly or via its main mediator, insulin-like growth factor1 (IGF1). In this study, we focused on the novel relationship between GH action and the antiaging hormone α-klotho. Immunofluorescent staining of α-klotho was observed in the renal distal tubules and pituitary glands of somatostatin- and GH-positive cells in wild-type (WT) mice. Treatment of 4-week-old WT mice with GH increased IGF1 mRNA expression in the pituitary gland, liver, heart, kidney, and bone but increased α-klotho mRNA expression only in the pituitary gland, kidney, and bone. Increased α-klotho protein levels were observed in the kidney but not in the pituitary gland. No induction of α-klotho RNA expression by GH was observed in juvenile mice with kidney disease, indicating GH resistance. Furthermore, GH and α-klotho supplementation in HEK293 cells transfected with GHR increased Janus kinase 2 mRNA (a GH downstream signal) expression compared to supple­mentation with GH alone. In conclusion, we suggest that 1) the kidney is the main source of secreted α-klotho, which is detected in blood by the downstream action of GH, 2) α-klotho induction by GH is resistant in kidney disease, and 3) α-klotho might be an enhanced regulator of GH signaling.</p>

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