Title

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

Document Type

Article

Publication Date

1-5-2017

Publication Title

Molecular and cellular endocrinology

Abstract

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.

Medical Subject Headings

Adrenal Glands; Child; Child, Preschool; Cytochrome P-450 CYP11B2; Female; Fluorescent Antibody Technique; Humans; Hyperaldosteronism; Immunohistochemistry; Male; Progesterone Reductase

PubMed ID

27793677

Volume

439

First Page

74

Last Page

80

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