Immunohistochemistry of aldosterone synthase leads the way to the pathogenesis of primary aldosteronism

Koshiro Nishimoto, Minae Koga, Tsugio Seki, Kenji Oki, Elise P. Gomez-Sanchez, Celso E. Gomez-Sanchez, Mitsuhide Naruse, Tomokazu Sakaguchi, Shinya Morita, Takeo Kosaka, Mototsugu Oya, Tadashi Ogishima, Masanori Yasuda, Makoto Suematsu, Yasuaki Kabe, Masao Omura, Tetsuo Nishikawa, Kuniaki Mukai

Research output: Contribution to journalReview article

23 Citations (Scopus)

Abstract

Our group previously purified human and rat aldosterone synthase (CYP11B2 and Cyp11b2, respectively) from their adrenals and verified that it is distinct from steroid 11β-hydroxylase (CYP11B1 or Cyp11b1), the cortisol- or corticosterone-synthesizing enzyme. We now describe their distributions immunohistochemically with specific antibodies. In rats, there is layered functional zonation with the Cyp11b2-positive zona glomerulosa (ZG), Cyp11b1-positive zona fasciculata (ZF), and Cyp11b2/Cyp11b1-negative undifferentiated zone between the ZG and ZF. In human infants and children (<12 years old), the functional zonation is similar to that in rats. In adults, the adrenal cortex remodels and subcapsular aldosterone-producing cell clusters (APCCs) replace the continuous ZG layer. We recently reported possible APCC-to-APA transitional lesions (pAATLs) in 2 cases of unilateral multiple adrenocortical micro-nodules. In this review, we present 4 additional cases of primary aldosteronism, from which the extracted adrenals contain pAATLs, with results of next generation sequencing for these lesions. Immunohistochemistry for CYP11B2 and CYP11B1 has become an important tool for the diagnosis of and research on adrenocortical pathological conditions and suggests that APCCs may be the origin of aldosterone-producing adenoma.

Original languageEnglish
Pages (from-to)124-133
Number of pages10
JournalMolecular and Cellular Endocrinology
Volume441
DOIs
Publication statusPublished - 2017 Feb 5

Keywords

  • Aldosterone synthase (CYP11B2)
  • Aldosterone-producing cell cluster (APCC)
  • Human adrenal
  • Immunohistochemistry
  • Possible APCC-to-APA transitional lesion (pAATL)
  • Rat adrenal

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

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  • Cite this

    Nishimoto, K., Koga, M., Seki, T., Oki, K., Gomez-Sanchez, E. P., Gomez-Sanchez, C. E., Naruse, M., Sakaguchi, T., Morita, S., Kosaka, T., Oya, M., Ogishima, T., Yasuda, M., Suematsu, M., Kabe, Y., Omura, M., Nishikawa, T., & Mukai, K. (2017). Immunohistochemistry of aldosterone synthase leads the way to the pathogenesis of primary aldosteronism. Molecular and Cellular Endocrinology, 441, 124-133. https://doi.org/10.1016/j.mce.2016.10.014