Disordered zonal and cellular CYP11B2 enzyme expression in familial hyperaldosteronism type 3

MOLECULAR AND CELLULAR ENDOCRINOLOGY

卷:439

Article

Gomez-Sanchez, Celso E.^1,2  Qi, Xin²  Gomez-Sanchez, Elise P.³  Sasano, Hironobu⁴  Bohlen, Martin O.⁵  Wisgerhof, Max⁶ 

[1] GV Sonny Montgomery VA Med Ctr, Div Endocrinol, Jackson, MS USA

[2] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA

[3] Univ Mississippi, Med Ctr, Dept Pharmacol & Toxicol & Med, Jackson, MS 39216 USA

[4] Tohoku Univ, Dept Pathol, Sendai, Miyagi, Japan

[5] Univ Mississippi, Med Ctr, Dept Anat Sci, Jackson, MS 39216 USA

[6] Henry Ford Hlth Syst, Div Endocrinol, Detroit, MI USA

关键词: Primary aldosteronism;    Aldosterone;    CYP11B2;    KCNJ5;    CYP17A1;   

DOI  :  10.1016/j.mce.2016.10.025

来源: Elsevier

【 摘 要 】

Three forms of familial primary aldosteronism have been recognized. Familial Hyperaldosteronism type 1 (FH1) or dexamethasone suppressible hyperaldosteronism, FH2, the most common form of as yet unknown cause(s), and FH3. FH3 is due to activating mutations of the potassium channel gene KCNJ5 that increase constitutive and angiotensin II-induced aldosterone synthesis. In this study we examined the cellular distribution of CYP11B2, CYP11B1, CYP17A1 and KCNJ5 in adrenals from two FH3 siblings using immunohistochemistry and immunofluorescence and obtained unexpected results. The adrenals were markedly enlarged with loss of zonation. CYP11B2 was expressed sporadically throughout the adrenal cortex. CYP11B2 was most often expressed by itself, relatively frequently with CYP17A1, and less frequently with CYP11B1. KCNJ5 was co-expressed with CYP11B2 and in some cells with CYP11B1. This aberrant co-expression of enzymes likely explains the abnormally high secretion rate of the hybrid steroid, 18-oxocortisol. Published by Elsevier Ireland Ltd.

【 授权许可】

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