TY - JOUR
T1 - Immunohistochemistry of aldosterone synthase leads the way to the pathogenesis of primary aldosteronism
AU - Nishimoto, Koshiro
AU - Koga, Minae
AU - Seki, Tsugio
AU - Oki, Kenji
AU - Gomez-Sanchez, Elise P.
AU - Gomez-Sanchez, Celso E.
AU - Naruse, Mitsuhide
AU - Sakaguchi, Tomokazu
AU - Morita, Shinya
AU - Kosaka, Takeo
AU - Oya, Mototsugu
AU - Ogishima, Tadashi
AU - Yasuda, Masanori
AU - Suematsu, Makoto
AU - Kabe, Yasuaki
AU - Omura, Masao
AU - Nishikawa, Tetsuo
AU - Mukai, Kuniaki
N1 - Publisher Copyright:
© 2016 Elsevier Ireland Ltd
PY - 2017/2/5
Y1 - 2017/2/5
N2 - 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.
AB - 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.
KW - Aldosterone synthase (CYP11B2)
KW - Aldosterone-producing cell cluster (APCC)
KW - Human adrenal
KW - Immunohistochemistry
KW - Possible APCC-to-APA transitional lesion (pAATL)
KW - Rat adrenal
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U2 - 10.1016/j.mce.2016.10.014
DO - 10.1016/j.mce.2016.10.014
M3 - Review article
C2 - 27751767
AN - SCOPUS:85008704872
SN - 0303-7207
VL - 441
SP - 124
EP - 133
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
ER -