Endocrine Pathology

, Volume 25, Issue 3, pp 229–235 | Cite as

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

  • Saulo J. A. Felizola
  • Yasuhiro Nakamura
  • Yuki Arata
  • Kazue Ise
  • Fumitoshi Satoh
  • William E. Rainey
  • Sanae Midorikawa
  • Shinichi Suzuki
  • Hironobu Sasano


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.


Adrenal cortex Zona glomerulosa Adrenocortical adenoma Aldosterone Metallothionein Immunohistochemistry 



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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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Saulo J. A. Felizola
    • 1
  • Yasuhiro Nakamura
    • 1
  • Yuki Arata
    • 1
  • Kazue Ise
    • 1
  • Fumitoshi Satoh
    • 2
  • William E. Rainey
    • 3
  • Sanae Midorikawa
    • 4
  • Shinichi Suzuki
    • 5
  • Hironobu Sasano
    • 1
  1. 1.Department of PathologyTohoku University Graduate School of MedicineSendaiJapan
  2. 2.Division of Nephrology, Endocrinology and Vascular MedicineTohoku University HospitalSendaiJapan
  3. 3.Department of Physiology and MedicineUniversity of MichiganAnn ArborUSA
  4. 4.Department of Radiation Health ManagementFukushima Medical UniversityFukushimaJapan
  5. 5.Department of Organ Regulatory SurgeryFukushima Medical UniversityFukushimaJapan

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