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Metallothionein-3 (MT-3) in the Human Adrenal Cortex and its Disorders

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Abstract

Metallothionein-3 (MT-3) is an intracellular, low molecular weight protein mainly distributed in the central nervous system but also in various peripheral organs and several types of human neoplasms. However, details of MT-3 expression have not been examined in human adrenal cortex and its disorders. The mRNA levels of MT-3 were first evaluated by quantitative RT-PCR (qPCR) in adrenocortical aldosterone-producing adenoma (APA: 11) and cortisol-producing adenoma (CPA: 14). In addition, MT-3 immunohistochemistry was performed in non-pathological adrenal glands (NA: 19), idiopathic hyperaldosteronism (IHA: 10), APA (20), CPA (24), adjacent non-neoplastic adrenal glands of adenoma (AAG: 20), and adrenocortical carcinoma (ACC: 8). H295R cells were also treated with angiotensin-II or forskolin in a time-dependent manner, and the changes of MT-3 mRNA levels were evaluated by qPCR. Results of qPCR analysis demonstrated that MT-3 mRNA levels were significantly higher in APA than CPA (P = 0.0004). MT-3 immunoreactivity was detected in the zona glomerulosa of NA, IHA, and AAG, as well as in APA, CPA, and ACC. When treated with angiotensin-II and forskolin, MT-3 mRNA levels reached a peak by 12 h in H295R cells, with significantly higher levels compared to control non-treated cells (P < 0.01). The presence of MT-3 in the ZG of NA, IHA, and AAG, as well as APA may imply a role in the pathophysiology of aldosterone-producing tissues.

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Acknowledgments

This work was partly supported by the Takeda Science Foundation and partly supported by the grant for Research on Intractable Diseases from the Japanese Ministry of Health, Labor and Welfare. The first author received scholarship support from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT).

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Authors and Affiliations

  1. Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan

    Saulo J. A. Felizola, Yasuhiro Nakamura, Yuki Arata, Kazue Ise & Hironobu Sasano

  2. Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Hospital, Sendai, Japan

    Fumitoshi Satoh

  3. Department of Physiology and Medicine, University of Michigan, Ann Arbor, MI, USA

    William E. Rainey

  4. Department of Radiation Health Management, Fukushima Medical University, Fukushima, Japan

    Sanae Midorikawa

  5. Department of Organ Regulatory Surgery, Fukushima Medical University, Fukushima, Japan

    Shinichi Suzuki

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  1. Saulo J. A. Felizola
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Correspondence to Yasuhiro Nakamura.

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Felizola, S.J.A., Nakamura, Y., Arata, Y. et al. Metallothionein-3 (MT-3) in the Human Adrenal Cortex and its Disorders. Endocr Pathol 25, 229–235 (2014). https://doi.org/10.1007/s12022-013-9280-9

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