Document Detail

Adrenocortical zonation in humans under normal and pathological conditions.
MedLine Citation:
PMID:  20200334     Owner:  NLM     Status:  MEDLINE    
CONTEXT: Aldosterone synthase (CYP11B2) and steroid 11 beta-hydroxylase (CYP11B1) catalyze the terminal steps for aldosterone and cortisol syntheses, respectively, thereby determining the functional differentiation of human adrenocortical cells. Little is known, 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, and a CYP11B1-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.
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
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-03-03
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  95     ISSN:  1945-7197     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-05-06     Completed Date:  2010-05-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2296-305     Citation Subset:  AIM; IM    
Department of Urology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
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MeSH Terms
Adrenal Cortex / enzymology,  pathology*,  physiology*
Aldosterone / metabolism
Aldosterone Synthase / deficiency,  metabolism
Amino Acid Sequence
Carcinoma, Renal Cell / enzymology
Corticosterone / metabolism
Cushing Syndrome / enzymology
Kidney Neoplasms / enzymology
Peptide Fragments / chemistry
Reference Values
Steroid 11-beta-Hydroxylase / metabolism
Zona Fasciculata / enzymology
Zona Glomerulosa / enzymology
Reg. No./Substance:
0/Antibodies; 0/Peptide Fragments; 50-22-6/Corticosterone; 52-39-1/Aldosterone; EC Synthase; EC 11-beta-Hydroxylase

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