{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T04:40:07Z","timestamp":1790138407781,"version":"4.0.1"},"reference-count":36,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T00:00:00Z","timestamp":1730937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Society for the Promotion of Science (Grant-in-Aid for Young Scientists (B))","award":["21790889"],"award-info":[{"award-number":["21790889"]}]},{"name":"Ministry of Health, Labor and Welfare of Japan","award":["21790889"],"award-info":[{"award-number":["21790889"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The CYP11B2 gene is sporadically expressed in the zona glomerulosa (ZG), whereas the CYP11B1 gene is detected in the zona fasciculata (ZF)\/reticularis (ZR), with predominant expression in the ZF. We studied the association between DNA methylation and adrenal zonation. Next, the CYP11B2 methylation statuses in the adrenal medulla (n = 4) and pheochromocytomas (n = 7) were examined. The expression of CYP11B2 in pheochromocytomas and non-functioning adenomas (NFAs) (n = 4) was also studied. Adrenals from five autopsy subjects were assessed for immunohistochemically defined adrenal zonation. We used laser capture microscopy to isolate DNA from each zone in adrenal tissues. CYP11B1 was predominantly unmethylated in the ZF but heavily methylated in the ZG and the ZR. In contrast, CYP11B2 was hypomethylated in the ZG compared with in the ZF and the ZR. In terms of the expression site and strength, the promoter methylation patterns for CYP11B2 and CYP11B1 showed capacities to express CYP11B enzymes. The DNA methylation patterns of the CYP11B2 and CYP11B1 promoters were closely associated with adrenal zonation. The unmethylated CpGs of CYP11B2 were found in the adrenal medulla and pheochromocytomas. Gene expression of CYP11B2 was detected in the pheochromocytomas. These results indicate the possibility that the synthesis of aldosterone occurs in the adrenal medulla. Further study is necessary to elucidate the pathophysiological roles for the synthesis of aldosterone in the adrenal medulla.<\/jats:p>","DOI":"10.3390\/ijms252211956","type":"journal-article","created":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T04:22:56Z","timestamp":1730953376000},"page":"11956","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Epigenomic Alterations of the Human CYP11B Gene in Adrenal Zonation"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3780-3862","authenticated-orcid":false,"given":"Yoshimichi","family":"Takeda","sequence":"first","affiliation":[{"name":"Saiseikai Kanazawa Hospital, 13-6 Akadochyo-ni, Kanazawa 920-0353, Japan"},{"name":"Department of Health Promotion and Medicine of Future, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Demura","sequence":"additional","affiliation":[{"name":"Department of Hygiene, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8640, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Yoneda","sequence":"additional","affiliation":[{"name":"Department of Health Promotion and Medicine of Future, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4084-9653","authenticated-orcid":false,"given":"Shigehiro","family":"Karashima","sequence":"additional","affiliation":[{"name":"Department of Health Promotion and Medicine of Future, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0461-3018","authenticated-orcid":false,"given":"Mitsuhiro","family":"Kometani","sequence":"additional","affiliation":[{"name":"Department of Health Promotion and Medicine of Future, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Aono","sequence":"additional","affiliation":[{"name":"Department of Health Promotion and Medicine of Future, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seigo","family":"Konishi","sequence":"additional","affiliation":[{"name":"Department of Health Promotion and Medicine of Future, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4256-9129","authenticated-orcid":false,"given":"Shin-ichi","family":"Horike","sequence":"additional","affiliation":[{"name":"Division of Functional Genomics, Research Center for Experimental Modeling of Human Disease, 13-1 Takara-machi, Kanazawa 920-8640, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Division of Pathology, Tohoku Medical and Pharmaceutical University 1-15-1 Fukumuro, Miyaginoku, Sendai 983-8536, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuto","family":"Yamazaki","sequence":"additional","affiliation":[{"name":"Department of Pathology, Tohoku University Hospital, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironobu","family":"Sasano","sequence":"additional","affiliation":[{"name":"Department of Pathology, Tohoku University Hospital, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5670-8871","authenticated-orcid":false,"given":"Yoshiyu","family":"Takeda","sequence":"additional","affiliation":[{"name":"Department of Health Promotion and Medicine of Future, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan"},{"name":"Hypertension Center, Asanogawa General Hospital, 83 Kosakamachi-naka, Kanazawa 920-8621, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1210\/clinem\/dgae008","article-title":"Update on adrenarche-still a mystery","volume":"109","author":"Augsburger","year":"2024","journal-title":"J. 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