2. Academic Validation
  3. Growth hormone regulates deiodinase type 2 and 3 expression via GATA

Growth hormone regulates deiodinase type 2 and 3 expression via GATA

  • Growth Horm IGF Res. 2025 May 21:82:101659. doi: 10.1016/j.ghir.2025.101659.
Mana Mitsutani 1,  Hiromi Hano 2,  Mei Yokoyama 2,  Midori Matsushita 2,  Misa Hayashi 2,  Ichiro Yamauchi 3,  Tetsuya Tagami 4,  Kenji Moriyama 5
Affiliations

Affiliations

  • 1 Medicine & Clinical Science, Faculty of Pharmaceutical Sciences, Mukogawa Women's University, Hyogo 663-8179, Japan. Electronic address: hkrtn16@mukogawa-u.ac.jp.
  • 2 Medicine & Clinical Science, Faculty of Pharmaceutical Sciences, Mukogawa Women's University, Hyogo 663-8179, Japan.
  • 3 Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
  • 4 Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan; Clinical Research Institute for Endocrine and Metabolic Diseases, National Hospital Organization Kyoto Medical Center, Kyoto 612-8555, Japan.
  • 5 Medicine & Clinical Science, Faculty of Pharmaceutical Sciences, Mukogawa Women's University, Hyogo 663-8179, Japan; Clinical Research Institute for Endocrine and Metabolic Diseases, National Hospital Organization Kyoto Medical Center, Kyoto 612-8555, Japan.
PMID: 40413916 DOI: 10.1016/j.ghir.2025.101659
Abstract

Objective: Growth hormone (GH) is involved in bone and skeletal muscle growth directly or indirectly via STAT5 and/or insulin-like growth factor (IGF)-1. Thyroid hormone (TH) is essential for general cellular growth and metabolic regulation. While both GH and TH are essential for growth, their actions may partially complement each Other in conditions of hormonal deficiency. For example, TH can enhance GH secretion and sensitivity, while GH is ineffective in Refetoff syndrome due to TH receptor dysfunction. However, the underlying molecular mechanism remains unclear. In this study, we investigated the molecular mechanisms underlying the complementarity between GH and TH, paying special attention to the effects of GH on the expression of both iodothyronine deiodinase (DIO) type 2 (DIO2) and type 3 (DIO3).

Design: The effects of growth hormone (GH) on DIOs were examined using reporter assays, chromatin immunoprecipitation, quantitative PCR, and western blotting using HEK293-derived TSA201 cells and mouse ATDC5 chondrocytes.

Results: GH induced the mRNA and protein expression of DIOs in ATDC5 cells via STAT5/GATA. GATAs activate the promoter activity of both DIOs. The binding sites for GATA on the DIO promoter were located -87 bp and - 75 bp upstream from the TSS for the DIO2 promoter and - 6 bp upstream from the TSS for the DIO3 promoter, respectively. GH-induced expression of DIOs in ATDC5 cells was abolished by K-7174, a GATA-specific inhibitor.

Conclusion: The present study demonstrates that GH regulates DIO2 and DIO3 expression via JAK/STAT5/GATAs after binding to GHR. This is the first report on the molecular mechanisms underlying GH-dependent compensation of TH action. (256 words).

Keywords

Deiodinase; Growth hormone; Thyroid hormone.

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