{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:38:55Z","timestamp":1791923935087,"version":"4.3.4"},"reference-count":62,"publisher":"Georg Thieme Verlag KG","issue":"06","funder":[{"DOI":"10.13039\/501100000850","name":"National Heart and Lung Institute","doi-asserted-by":"crossref","award":["Grant No. R01 HL144847"],"award-info":[{"award-number":["Grant No. R01 HL144847"]}],"id":[{"id":"10.13039\/501100000850","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["Grant No. 1U54GM115428"],"award-info":[{"award-number":["Grant No. 1U54GM115428"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Horm Metab Res"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The CYP11B2 enzyme is the terminal enzyme in the biosynthesis of aldosterone.\n                    Immunohistochemistry using antibodies against CYP11B2 defines cells of the\n                    adrenal ZG that synthesize aldosterone. CYP11B2 expression is normally\n                    stimulated by angiotensin II, but becomes autonomous in primary\n                    hyperaldosteronism, in most cases driven by recently discovered somatic\n                    mutations of ion channels or pumps. Cells expressing CYP11B2 in young normal\n                    humans form a continuous band beneath the adrenal capsule; in older individuals\n                    they form discrete clusters, aldosterone-producing cell clusters (APCC),\n                    surrounded by non-aldosterone producing cells in the outer layer of the adrenal\n                    gland. Aldosterone-producing adenomas may exhibit a uniform or heterogeneous\n                    expression of CYP11B2. APCC frequently persist in the adrenal with an\n                    aldosterone-producing adenoma suggesting autonomous CYP11B2 expression in these\n                    cells as well. This was confirmed by finding known mutations that drive\n                    aldosterone production in adenomas in the APCC of clinically normal people.\n                    Unilateral aldosteronism may also be due to multiple CYP11B2-expressing nodules\n                    of various sizes or a continuous band of hyperplastic ZG cells expressing\n                    CYP11B2. Use of CYP11B2 antibodies to identify areas for sequencing has greatly\n                    facilitated the detection of aldosterone-driving mutations.<\/jats:p>","DOI":"10.1055\/a-1139-2079","type":"journal-article","created":{"date-parts":[[2020,4,14]],"date-time":"2020-04-14T22:57:21Z","timestamp":1586905041000},"page":"421-426","source":"Crossref","is-referenced-by-count":33,"title":["Immunohistochemistry of the Human Adrenal CYP11B2 in Normal\n                    Individuals and in Patients with Primary Aldosteronism"],"prefix":"10.1055","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9882-2082","authenticated-orcid":false,"given":"Celso E.","family":"Gomez-Sanchez","sequence":"additional","affiliation":[{"name":"G. V. (Sonny) Montgomery VA Medical Center, Jackson, MS,\n                    USA"},{"name":"Department of Pharmacology and Toxicology, University of Mississippi\n                    Medical Center, Jackson, MS, USA"},{"name":"Medicine (Endocrinology), University of Mississippi Medical Center,\n                    Jackson, MS, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4432-4950","authenticated-orcid":false,"given":"Elise P.","family":"Gomez-Sanchez","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Mississippi\n                    Medical Center, Jackson, MS, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koshiro","family":"Nishimoto","sequence":"additional","affiliation":[{"name":"Department of Uro-Oncology, Saitama Medical University International\n                    Medical Center, Saitama, Japan"},{"name":"Department of Biochemistry, Keio University School of Medicine, Tokyo,\n                    Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2020,4,14]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1210\/er.2010-0013","article-title":"The molecular biology, biochemistry, and physiology of human steroidogenesis and\n                    its disorders","volume":"32","author":"W L Miller","year":"2011","journal-title":"Endocr Rev"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/0006-2952(95)02093-4","article-title":"Role of the steroidogenic acute regulatory protein (StAR) in\n                    steroidogenesis","volume":"51","author":"D M Stocco","year":"1996","journal-title":"Biochem Pharm"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1002\/cphy.c130044","article-title":"The multifaceted mineralocorticoid receptor","volume":"4","author":"E Gomez-Sanchez","year":"2014","journal-title":"Compr Physiol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.steroids.2014.08.014","article-title":"Brain mineralocorticoid receptors in cognition and cardiovascular\n                    homeostasis","volume":"91","author":"E P Gomez-Sanchez","year":"2014","journal-title":"Steroids"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.mce.2011.07.034","article-title":"Acute and chronic regulation of aldosterone production","volume":"350","author":"N G Hattangady","year":"2012","journal-title":"Mol Cell Endocr"},{"key":"ref6","first-page":"1029","article-title":"The biology of normal zona glomerulosa and aldosterone-producing adenoma:\n                    Pathological implications","volume":"39","author":"T M Seccia","year":"2018","journal-title":"Endocr Rev"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/S2213-8587(17)30319-4","article-title":"Cardiovascular events and target organ damage in primary aldosteronism compared\n                    with essential hypertension: A systematic review and meta-analysis","volume":"6","author":"S Monticone","year":"2018","journal-title":"Lancet Diabetes Endocr"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1210\/jc.2015-4061","article-title":"The Management of Primary Aldosteronism: Case Detection, Diagnosis, and\n                    Treatment: An Endocrine Society Clinical Practice Guideline","volume":"101","author":"J W Funder","year":"2016","journal-title":"J Clin Endocrinol Metab"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1126\/science.1198785","article-title":"K+channel mutations in adrenal aldosterone-producing adenomas and\n                    hereditary hypertension","volume":"331","author":"M Choi","year":"2011","journal-title":"Science"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1038\/ng.2550","article-title":"Somatic mutations in ATP1A1 and ATP2B3 lead to aldosterone-producing adenomas\n                    and secondary hypertension","volume":"45","author":"F Beuschlein","year":"2013","journal-title":"Nat Genet"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1038\/ng.2695","article-title":"Somatic and germline CACNA1D calcium channel mutations in aldosterone-producing\n                    adenomas and primary aldosteronism","volume":"45","author":"U I Scholl","year":"2013","journal-title":"Nat Genet"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/s41588-018-0053-8","article-title":"A gain-of-function mutation in the CLCN2 chloride channel gene causes primary\n                    aldosteronism","volume":"50","author":"F L Fernandes-Rosa","year":"2018","journal-title":"Nat. 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