Immunohistochemical analysis of 11-β-hydroxysteroid dehydrogenase type 2 and glucocorticoid receptor in subclinical cushing's disease due to pituitary macroadenoma

Takanori Ebisawa, Katsuyoshi Tojo, Naoko Tajima, Masami Kamio, Yutaka Oki, Katsuhiko Ono, Hironobu Sasano

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9 Citations (Scopus)

Abstract

Subclinical Cushing's disease (SCD) is characterized by lack of clinically evident Cushingoid features, despite abnormal hypersecretion of ACTH. Nearly half the cases of SCD are due to macroadenomas, and in the majority of them, ACTH secretion is not inhibited even by high-dose dexamethasone. Impaired glucocorticoid (GC) action may be correlated with the proliferation and development of pituitary macroadenomas causing SCD. In this study, immunohistochemical analysis of the resected tumors were performed to evaluate the expression of 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) and glucocorticoid receptor (GR) in pituitary tissues obtained from two SCD (macroadenomas), eight Cushing's disease (CD) (microadenomas), nine acromegaly, and nine normal pituitary (NP). Scattered 11βHSD2-immunopositive cells were detected in all NP tissues, but its immunoreactivity was totally absent in any tumorous tissues except two CD. Scattered GR-immunopositive cells were also detected and GR immunostaining was restricted to the cytosol in NP tissue. In contrast, GR-immunopositive cells were abundantly present and GR immunostaining was restricted to the nucleus in all the tumorous tissues. There were marked differences in both expression levels and localization between NP tissues and all the tumors. There may be a mechanism other than that via 11βHSD2 for causes of impaired negative feedback action by GC in SCD and CD, but results of our present study suggest that impaired GC action may be involved, at least in part, in tumorigenesis of SCD and CD.

Original languageEnglish
Pages (from-to)252-260
Number of pages9
JournalEndocrine Pathology
Volume19
Issue number4
DOIs
Publication statusPublished - 2008 Dec

Keywords

  • 11β- hydroxysteroid dehydrogenase type 2
  • ACTH
  • Glucocorticoid receptor
  • Immunohistochemistry
  • Pituitary macroadenoma
  • Subclinical Cushing's disease

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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