title: Disordered zonal and cellular CYP11B2 enzyme expression in familial hyperaldosteronism type 3.
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.
authors: Endocrinology Division, G.V. (Sonny) Montgomery VA Medical Center, Jackson, MS, United States; University of Mississippi Medical Center, Jackson, MS, United States. Electronic address: cgomez-sanchez@umc.edu.
authors: Celso E
authors: CE
authors: Gomez-Sanchez
authors: University of Mississippi Medical Center, Jackson, MS, United States.
authors: Xin
authors: X
authors: Qi
authors: Department of Pharmacology and Toxicology and Medicine, University of Mississippi Medical Center, Jackson, MS, United States.
authors: Elise P
authors: EP
authors: Gomez-Sanchez
authors: Department of Pathology, Tohoku University, Sendai, Japan.
authors: Hironobu
authors: H
authors: Sasano
authors: Department of Anatomical Sciences, University of Mississippi Medical Center, Jackson, MS, United States.
authors: Martin O
authors: MO
authors: Bohlen
authors: Division of Endocrinology, Henry Ford Health System, Detroit, MI, United States.
authors: Max
authors: M
authors: Wisgerhof
mesh_terms: D000311:Adrenal Glands / Q000201:enzymology / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D019405:Cytochrome P-450 CYP11B2 / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D006929:Hyperaldosteronism / Q000201:enzymology* / Q000473:pathology*; D007150:Immunohistochemistry; D008297:Male; D011375:Progesterone Reductase / Q000378:metabolism
chemical_list: C533068:3 beta-hydroxysteroid dehydrogenase type II; D011375:Progesterone Reductase; D019405:Cytochrome P-450 CYP11B2
keywords: Aldosterone; CYP11B2; CYP17A1; KCNJ5; Primary aldosteronism