Role of local 11 beta-hydroxysteroid dehydrogenase type 2 expression in determiningthe phenotype of adrenal adenomas.
Journal Title: Journal of Clinical Endocrinology and Metabolism - Year 2003, Vol 88, Issue 2
Abstract
It is not understood why some adrenal adenomas are nonfunctional and otherswith similar histopathology cause preclinical or overt Cushing's syndrome. Two isozymes of 11 beta-hydroxysteroiddehydrogenase, types 1 and 2 (HSD11B1 and HSD11B2), are known to modulate glucocorticoid levels in othertissues and might influence circulating levels of active and inactive glucocorticoids if they were expressedin adrenal adenomas. We determined levels of expression of these isozymes in normal adrenals and 61 adrenaladenomas by quantitative competitive RT-PCR and immunohistochemistry. There were no differences in HSD11B1mRNA levels among adrenal tumor groups. HSD11B2 mRNA levels were high in nonfunctioning adenomas andpreclinical Cushing's adenomas compared with levels in control adrenals or in adenomas causing overtCushing's syndrome. HSD11B2 immunoreactivity was not detected in control adrenals, but was observed inmore than half of these tumors. When nonfunctioning adenomas and those causing preclinical and overtCushing's syndrome were considered as a single group, HSD11B2 mRNA levels were strongly correlated withthe ratio of plasma cortisone to cortisol, and a simple model incorporating adrenal HSD11B2 expressionand tumor size as variables could predict more than 50% of the interindividual variation in plasma cortisollevels (r(2) = 0.54; P < 0.0001). Adrenal HSD11B2 may regulate levels of active and inactive glucocorticoidsin the systemic circulation under these conditions, presumably by acting in an autocrine or paracrinemanner. Nonfunctioning adenomas and those causing preclinical and overt Cushing's syndrome may representa continuum with clinical manifestations depending mainly on tumor size and HSD11B2 expression levels.
Authors and Affiliations
Tomoatsu Mune, Hiroyuki Morita, Takashi Suzuki, Yoshihito Takahashi, Yukinori Isomura, Tetsuya Tanahashi, Hisashi Daido, Noriyoshi Yamakita, Hironobu Sasano, Perrin C White, Keigo Yasuda
Keywords
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Role of local 11 beta-hydroxysteroid dehydrogenase type 2 expression in determiningthe phenotype of adrenal adenomas.
It is not understood why some adrenal adenomas are nonfunctional and otherswith similar histopathology cause preclinical or overt Cushing's syndrome. Two isozymes of 11 beta-hydroxysteroiddehydrogenase, types 1 and 2 (HS...