Role of local 11β-hydroxysteroid dehydrogenase type 2 expression in determining the phenotype of adrenal adenomas

Tomoatsu Mune, Hiroyuki Morita, Takashi Suzuki, Yoshihito Takahashi, Yukinori Isomura, Tetsuya Tanahashi, Hisashi Daido, Noriyoshi Yamakita, Takashi Deguchi, Hironobu Sasano, Perrin C. White, Keigo Yasuda

研究成果: Article査読

15 被引用数 (Scopus)

抄録

It is not understood why some adrenal adenomas are non-functional and others with similar histopathology cause preclinical or overt Cushing's syndrome. Two isozymes of 11β-hydroxysteroid dehydrogenase, types 1 and 2 (HSD11B1 and HSD11B2), are known to modulate glucocorticoid levels in other tissues and might influence circulating levels of active and inactive glucocorticoids if they were expressed in adrenal adenomas. We determined levels of expression of these isozymes in normal adrenals and 61 adrenal adenomas by quantitative competitive RT-PCR and immunohistochemistry. There were no differences in HSD11B1 mRNA levels among adrenal tumor groups. HSD11B2 mRNA levels were high in nonfunctioning adenomas and preclinical Cushing's adenomas compared with levels in control adrenals or in adenomas causing overt Cushing's syndrome. HSD11B2 immunoreactivity was not detected in control adrenals, but was observed in more than half of these tumors. When nonfunctioning adenomas and those causing preclinical and overt Cushing's syndrome were considered as a single group, HSD11B2 mRNA levels were strongly correlated with the ratio of plasma cortisone to cortisol, and a simple model incorporating adrenal HSD11B2 expression and tumor size as variables could predict more than 50% of the interindividual variation in plasma cortisol levels (r2 = 0.54; P < 0.0001). Adrenal HSD11B2 may regulate levels of active and inactive glucocorticoids in the systemic circulation under these conditions, presumably by acting in an autocrine or paracrine manner. Nonfunctioning adenomas and those causing preclinical and overt Cushing's syndrome may represent a continuum with clinical manifestations depending mainly on tumor size and HSD11B2 expression levels.

本文言語English
ページ(範囲)864-870
ページ数7
ジャーナルJournal of Clinical Endocrinology and Metabolism
88
2
DOI
出版ステータスPublished - 2003 2 1

ASJC Scopus subject areas

  • 内分泌学、糖尿病および代謝内科学
  • 生化学
  • 内分泌学
  • 臨床生化学
  • 生化学、医学

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