title: Immunohistochemistry of aldosterone synthase leads the way to the pathogenesis of primary aldosteronism.
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.
authors.affiliation: Department of Uro-Oncology, Saitama Medical University International Medical Center, Hidaka 350-1241, Japan; Department of Biochemistry, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. Electronic address: k.nishimoto@keio.jp.
authors.forename: Koshiro
authors.initials: K
authors.lastname: Nishimoto
authors.affiliation: Endocrinology & Diabetes Center, Yokohama Rosai Hospital, Yokohama 222-0036, Japan.
authors.forename: Minae
authors.initials: M
authors.lastname: Koga
authors.affiliation: Department of Medical Education, School of Medicine, California University of Science and Medicine, 1405 West Valley Blvd #101, Colton, CA 92324, USA.
authors.forename: Tsugio
authors.initials: T
authors.lastname: Seki
authors.affiliation: Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Oki
authors.affiliation: Department of Pharmacology & Toxicology, University of Mississippi Medical Center, Jackson, MS 39216, USA.
authors.forename: Elise P
authors.initials: EP
authors.lastname: Gomez-Sanchez
authors.affiliation: Endocrinology Section, G.V. (Sonny) Montgomery VA Medical Center and University of Mississippi Medical Center, Jackson, MS 39216, USA.
authors.forename: Celso E
authors.initials: CE
authors.lastname: Gomez-Sanchez
authors.affiliation: Department of Endocrinology, Metabolism and Hypertension, Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto 612-8555, Japan.
authors.forename: Mitsuhide
authors.initials: M
authors.lastname: Naruse
authors.affiliation: Department of Surgery, Misato Kenwa Hospital, 4-494-1 Takano, Misato, Saitama 341-8555, Japan.
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Sakaguchi
authors.affiliation: Department of Urology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Morita
authors.affiliation: Department of Urology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Kosaka
authors.affiliation: Department of Urology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Mototsugu
authors.initials: M
authors.lastname: Oya
authors.affiliation: Department of Chemistry, Faculty of Sciences, Kyushu University, Fukuoka 819-0395, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ogishima
authors.affiliation: Department of Pathology, Saitama Medical University International Medical Center, Hidaka 350-1241, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Yasuda
authors.affiliation: Department of Biochemistry, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Suematsu
authors.affiliation: Department of Biochemistry, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Kabe
authors.affiliation: Endocrinology & Diabetes Center, Yokohama Rosai Hospital, Yokohama 222-0036, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Omura
authors.affiliation: Endocrinology & Diabetes Center, Yokohama Rosai Hospital, Yokohama 222-0036, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Nishikawa
authors.affiliation: Department of Biochemistry, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan; Department of Medical Education Center, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Mukai
mesh_terms: D000450:Aldosterone / Q000096:biosynthesis; D000818:Animals; D055162:Biocatalysis; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics / Q000378:metabolism*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D006929:Hyperaldosteronism / Q000201:enzymology* / Q000473:pathology*; D007150:Immunohistochemistry / Q000379:methods*
chemical_list: D000450:Aldosterone; D019405:Cytochrome P-450 CYP11B2
keywords: Aldosterone synthase (CYP11B2); Aldosterone-producing cell cluster (APCC); Human adrenal; Immunohistochemistry; Possible APCC-to-APA transitional lesion (pAATL); Rat adrenal