title: Human Adrenocortical Remodeling Leading to Aldosterone-Producing Cell Cluster Generation.
abstract: Background. The immunohistochemical detection of aldosterone synthase (CYP11B2) and steroid 11β-hydroxylase (CYP11B1) has enabled the identification of aldosterone-producing cell clusters (APCCs) in the subcapsular portion of the human adult adrenal cortex. We hypothesized that adrenals have layered zonation in early postnatal stages and are remodeled to possess APCCs over time.Purposes. To investigate changes in human adrenocortical zonation with age.Methods. We retrospectively analyzed adrenal tissues prepared from 33 autopsied patients aged between 0 and 50 years. They were immunostained for CYP11B2 and CYP11B1. The percentage of APCC areas over the whole adrenal area (AA/WAA, %) and the number of APCCs (NOA, APCCs/mm2) were calculated by four examiners. Average values were used in statistical analyses.Results. Adrenals under 11 years old had layered zona glomerulosa (ZG) and zona fasciculata (ZF) without apparent APCCs. Some adrenals had an unstained (CYP11B2/CYP11B1-negative) layer between ZG and ZF, resembling the rat undifferentiated cell zone. Average AA/WAA and NOA correlated with age, suggesting that APCC development is associated with aging. Possible APCC-to-APA transitional lesions were incidentally identified in two adult adrenals.Conclusions. The adrenal cortex with layered zonation remodels to possess APCCs over time. APCC generation may be associated with hypertension in adults.
authors.affiliation: Department of Uro-Oncology, Saitama Medical University International Medical Center, Hidaka, Japan; Department of Biochemistry, Keio University School of Medicine, Shinjuku-ku, Japan.
authors.forename: Koshiro
authors.identifier: 0000-0002-3952-5643
authors.initials: K
authors.lastname: Nishimoto
authors.affiliation: Department of Medical Education, School of Medicine, California University of Science and Medicine, Colton, CA, USA.
authors.forename: Tsugio
authors.identifier: 0000-0002-3064-657X
authors.initials: T
authors.lastname: Seki
authors.affiliation: Division of Diagnostic Pathology, Keio University School of Medicine, Shinjuku-ku, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Hayashi
authors.affiliation: Division of Diagnostic Pathology, Keio University School of Medicine, Shinjuku-ku, Japan.
authors.forename: Shuji
authors.identifier: 0000-0002-2978-2187
authors.initials: S
authors.lastname: Mikami
authors.affiliation: Department of Medical Education, School of Medicine, California University of Science and Medicine, Colton, CA, USA.
authors.forename: Ghaith
authors.initials: G
authors.lastname: Al-Eyd
authors.affiliation: Department of Urology, Ichikawa General Hospital, Tokyo Dental College, Ichikawa, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Nakagawa
authors.affiliation: Department of Urology, Keio University School of Medicine, Shinjuku-ku, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Morita
authors.affiliation: Department of Urology, Keio University School of Medicine, Shinjuku-ku, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Kosaka
authors.affiliation: Department of Urology, Keio University School of Medicine, Shinjuku-ku, Japan.
authors.forename: Mototsugu
authors.initials: M
authors.lastname: Oya
authors.affiliation: Department of Biochemistry, Keio University School of Medicine, Shinjuku-ku, Japan.
authors.forename: Fumiko
authors.initials: F
authors.lastname: Mitani
authors.affiliation: Department of Biochemistry, Keio University School of Medicine, Shinjuku-ku, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Suematsu
authors.affiliation: Department of Biochemistry, Keio University School of Medicine, Shinjuku-ku, Japan.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Kabe
authors.affiliation: Department of Biochemistry, Keio University School of Medicine, Shinjuku-ku, Japan; Medical Education Center, Keio University School of Medicine, Shinjuku-ku, Japan.
authors.forename: Kuniaki
authors.identifier: 0000-0002-9590-5077
authors.initials: K
authors.lastname: Mukai