{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:55:19Z","timestamp":1763600119781,"version":"build-2065373602"},"reference-count":56,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,2,22]],"date-time":"2024-02-22T00:00:00Z","timestamp":1708560000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Adrenal myelolipomas (AML) are composed of mature adipose and hematopoietic components. They represent approximately 3 percent of adrenal tumors and are commonly found in patients with congenital adrenal hyperplasia (CAH). CAH provides a unique environment to explore AML pathogenesis. We aimed to evaluate the role of the immune system and hormones that accumulate in poorly controlled CAH in the development of AML. When compared to normal adrenal tissue, CAH-affected adrenal tissue and myelolipomas showed an increased expression of inflammatory cells (CD68, IL2Rbeta), stem cells (CD117) B cells (IRF4), and adipogenic markers (aP2\/FABP4, AdipoQ, PPAR\u03b3, Leptin, CideA), and immunostaining showed nodular lymphocytic accumulation. Immunohistochemistry staining revealed a higher density of inflammatory cells (CD20, CD3, CD68) in CAH compared to non-CAH myelolipomas. In vitro RNA-sequencing studies using NCI-H295R adrenocortical cells with exogenous exposure to ACTH, testosterone, and 17-hydroxyprogesterone hormones, showed the differential expression of genes involved in cell cycle progression, phosphorylation, and tumorigenesis. Migration of B-lymphocytes was initiated after the hormonal treatment of adrenocortical cells using the Boyden chamber chemotaxis assay, indicating a possible hormonal influence on triggering inflammation and the development of myelolipomas. These findings demonstrate the important role of inflammation and the hormonal milieu in the development of AML in CAH.<\/jats:p>","DOI":"10.3390\/ijms25052543","type":"journal-article","created":{"date-parts":[[2024,2,22]],"date-time":"2024-02-22T03:30:26Z","timestamp":1708572626000},"page":"2543","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Evidence of the Role of Inflammation and the Hormonal Environment in the Pathogenesis of Adrenal Myelolipomas in Congenital Adrenal Hyperplasia"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1175-8269","authenticated-orcid":false,"given":"Vipula","family":"Kolli","sequence":"first","affiliation":[{"name":"National Institutes of Health Clinical Center, 10 Center Drive, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily","family":"Frucci","sequence":"additional","affiliation":[{"name":"National Institutes of Health Clinical Center, 10 Center Drive, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabela Werneck","family":"da Cunha","sequence":"additional","affiliation":[{"name":"Laboratory of Pathology, National Cancer Institute, Bethesda, MD 20892, USA"},{"name":"D\u2019Or Institute for Research and Education (IDOR), S\u00e3o Paulo 05403, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James R.","family":"Iben","sequence":"additional","affiliation":[{"name":"The Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sun A.","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory of Pathology, National Cancer Institute, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashwini","family":"Mallappa","sequence":"additional","affiliation":[{"name":"National Institutes of Health Clinical Center, 10 Center Drive, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianwei","family":"Li","sequence":"additional","affiliation":[{"name":"The Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7959-9842","authenticated-orcid":false,"given":"Fabio Rueda","family":"Faucz","sequence":"additional","affiliation":[{"name":"The Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Electron","family":"Kebebew","sequence":"additional","affiliation":[{"name":"Division of General Surgery, Department of Surgery, Stanford University School of Medicine, Palo Alto, CA 94304, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naris","family":"Nilubol","sequence":"additional","affiliation":[{"name":"National Cancer Institute, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martha M.","family":"Quezado","sequence":"additional","affiliation":[{"name":"Laboratory of Pathology, National Cancer Institute, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3746-0460","authenticated-orcid":false,"given":"Deborah P.","family":"Merke","sequence":"additional","affiliation":[{"name":"National Institutes of Health Clinical Center, 10 Center Drive, Bethesda, MD 20892, USA"},{"name":"The Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1002\/1097-0142(197910)44:4<1350::AID-CNCR2820440428>3.0.CO;2-Y","article-title":"Myelolipoma in a heterotopic adrenal gland: Light and electron microscopic findings","volume":"44","author":"Damjanov","year":"1979","journal-title":"Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"94","DOI":"10.4103\/0970-1591.152807","article-title":"Adrenal myelolipoma: Controversies in its management","volume":"31","author":"Shenoy","year":"2015","journal-title":"Indian J. 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