title: Adrenocortical zonation in humans under normal and pathological conditions.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Urology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Koshiro
authors.initials: K
authors.lastname: Nishimoto
authors.forename: Ken
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.forename: Takeo
authors.initials: T
authors.lastname: Kosaka
authors.forename: Mototsugu
authors.initials: M
authors.lastname: Oya
authors.forename: Shuji
authors.initials: S
authors.lastname: Mikami
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Shibata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Itoh
authors.forename: Fumiko
authors.initials: F
authors.lastname: Mitani
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ogishima
authors.forename: Makoto
authors.initials: M
authors.lastname: Suematsu
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Mukai
mesh_terms: D000302:Adrenal Cortex / Q000201:enzymology / Q000473:pathology* / Q000502:physiology*; D000450:Aldosterone / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D002292:Carcinoma, Renal Cell / Q000201:enzymology; D003345:Corticosterone / Q000378:metabolism; D003480:Cushing Syndrome / Q000201:enzymology; D019405:Cytochrome P-450 CYP11B2 / Q000172:deficiency / Q000378:metabolism; D006801:Humans; D007680:Kidney Neoplasms / Q000201:enzymology; D008322:Mammals; D010446:Peptide Fragments / Q000737:chemistry; D011817:Rabbits; D012016:Reference Values; D012377:Rodentia; D013252:Steroid 11-beta-Hydroxylase / Q000378:metabolism; D015383:Zona Fasciculata / Q000201:enzymology; D015384:Zona Glomerulosa / Q000201:enzymology
chemical_list: D000906:Antibodies; D010446:Peptide Fragments; D000450:Aldosterone; D019405:Cytochrome P-450 CYP11B2; D013252:Steroid 11-beta-Hydroxylase; D003345:Corticosterone