title: Role of local 11 beta-hydroxysteroid dehydrogenase type 2 expression in determining the phenotype of adrenal adenomas.
abstract: It is not understood why some adrenal adenomas are nonfunctional and others with similar histopathology cause preclinical or overt Cushing's syndrome. Two isozymes of 11 beta-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 (r(2) = 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.
authors.affiliation: Third Department of Internal Medicine, Gifu University School of Medicine, Gifu 500-8705, Japan. mune@cc.gifu-u.ac.jp
authors.forename: Tomoatsu
authors.initials: T
authors.lastname: Mune
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Morita
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Isomura
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tanahashi
authors.forename: Hisashi
authors.initials: H
authors.lastname: Daido
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Yamakita
authors.forename: Takashi
authors.initials: T
authors.lastname: Deguchi
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
authors.forename: Perrin C
authors.initials: PC
authors.lastname: White
authors.forename: Keigo
authors.initials: K
authors.lastname: Yasuda
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D042842:11-beta-Hydroxysteroid Dehydrogenases; D000236:Adenoma / Q000201:enzymology* / Q000503:physiopathology; D000306:Adrenal Cortex Neoplasms / Q000201:enzymology* / Q000503:physiopathology; D000328:Adult; D000368:Aged; D003480:Cushing Syndrome / Q000201:enzymology / Q000503:physiopathology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000032:analysis / Q000235:genetics*; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D012333:RNA, Messenger; D006913:Hydroxysteroid Dehydrogenases; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D042842:11-beta-Hydroxysteroid Dehydrogenases; C468387:HSD11B2 protein, human