Adrenocortical zonation in humans under normal and pathological conditions

Koshiro Nishimoto, Ken Nakagawa, Dan Li, Takeo Kosaka, Mototsugu Oya, Shuji Mikami, Hirotaka Shibata, Hiroshi Itoh, Fumiko Mitani, Takeshi Yamazaki, Tadashi Ogishima, Makoto Suematsu, Kuniaki Mukai

Research output: Contribution to journalArticle

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Abstract

Context: Aldosterone synthase (CYP11B2) and steroid 11β-hydroxylase (CYP11B1) catalyze the terminal steps for aldosterone and cortisol syntheses, respectively, thereby determining the functional differentiationofhumanadrenocortical cells. Little isknown, however, about how the cells expressing the enzymes are actually distributed in the adrenals under normal and pathological conditions. Objective: The objective of the study was to determine the localization of CYP11B2 and -B1 in human adrenal specimens by using developed antibodies capable of distinguishing the two enzymes from each other. Results: Under normal conditions, CYP11B2 was sporadically detected in the zona glomerulosa, whereas CYP11B1 was entirely detected in the zonae fasciculata-reticularis. Adrenocortical cells lacking both enzymes were observed in the outer cortical regions. In addition to conventional zonation, we found a variegated zonation consisting of a subcapsular cell cluster expressing CYP11B2, which we termed aldosterone-producing cell cluster,andaCYP11B1- expressing area. Aldosterone-producing adenomas differed in cell populations expressing CYP11B2 from one another, whereas CYP11B1-expressing and double-negative cells were also intermingled. Adenomas from patients with Cushing's syndrome expressed CYP11B1 entirely but not CYP11B2, resulting in atrophic nontumor glands. The nontumor portions of both types of adenomas bore frequently one or more aldosterone-producing cell clusters, which sustained CYP11B2 expression markedly under the conditions of the suppressed renin-angiotensin system. Conclusion: Immunohistochemistry of the human normal adrenal cortex for CYP11B2 and CYP11B1 revealed a variegated zonation with cell clusters constitutively expressing CYP11B2. This technique may provide a pathological confirmatory diagnosis of adrenocortical adenomas.

Original languageEnglish
Pages (from-to)2296-2305
Number of pages10
JournalJournal of Clinical Endocrinology and Metabolism
Volume95
Issue number5
DOIs
Publication statusPublished - 2010 May

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Cytochrome P-450 CYP11B2
Steroid 11-beta-Hydroxylase
Aldosterone
Adenoma
Enzymes
Zona Reticularis
Cells
Adrenocortical Adenoma
Zona Fasciculata
Zona Glomerulosa
Cushing Syndrome
Adrenal Cortex
Angiotensins
Renin-Angiotensin System

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)

Cite this

Adrenocortical zonation in humans under normal and pathological conditions. / Nishimoto, Koshiro; Nakagawa, Ken; Li, Dan; Kosaka, Takeo; Oya, Mototsugu; Mikami, Shuji; Shibata, Hirotaka; Itoh, Hiroshi; Mitani, Fumiko; Yamazaki, Takeshi; Ogishima, Tadashi; Suematsu, Makoto; Mukai, Kuniaki.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 95, No. 5, 05.2010, p. 2296-2305.

Research output: Contribution to journalArticle

Nishimoto, Koshiro ; Nakagawa, Ken ; Li, Dan ; Kosaka, Takeo ; Oya, Mototsugu ; Mikami, Shuji ; Shibata, Hirotaka ; Itoh, Hiroshi ; Mitani, Fumiko ; Yamazaki, Takeshi ; Ogishima, Tadashi ; Suematsu, Makoto ; Mukai, Kuniaki. / Adrenocortical zonation in humans under normal and pathological conditions. In: Journal of Clinical Endocrinology and Metabolism. 2010 ; Vol. 95, No. 5. pp. 2296-2305.
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