{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T21:08:16Z","timestamp":1791839296794,"version":"4.3.4"},"reference-count":82,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Centre in Poland","award":["2020\/38\/E\/NZ4\/00020"],"award-info":[{"award-number":["2020\/38\/E\/NZ4\/00020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>The hypothalamic\u2013pituitary\u2013adrenal (HPA) axis plays a pivotal role in regulating stress responses through ACTH-stimulated glucocorticoid production. The transcriptional programmes underlying temporal adaptation to prolonged ACTH exposure and glucocorticoid feedback remain incompletely characterized. Adult male Wistar rats were subjected to acute ACTH stimulation (single injection, 1 h) to elicit an immediate transcriptional response, prolonged ACTH exposure (three injections over 36 h) as a repeated exposure, or Dexamethasone treatment (three injections over 36 h). Plasma corticosterone levels were subsequently measured using an enzyme-linked immunosorbent assay (ELISA). The adrenal transcriptome profiling was performed using Affymetrix arrays. Differentially expressed genes (DEGs; |fold change| \u2265 1.8, adjusted p &lt; 0.05) were analyzed using limma, followed by pathway and network analyses. Acute ACTH exposure resulted in the induction of 569 DEGs (357 upregulated), including immediate-early genes (Nr4a family, AP-1 factors), cAMP-PKA-CREB signalling components, and heat shock proteins. Prolonged ACTH resulted in 98 DEGs (predominantly downregulated), including the suppression of mitochondrial genes and upregulation of Polycomb repressive complex 2 components, suggesting epigenetic transcriptional attenuation. Dexamethasone treatment yielded 75 DEGs with selective suppression of SREBP-mediated cholesterol biosynthesis and uptake pathways. Twelve genes were downregulated by both prolonged ACTH and Dexamethasone, including sterol metabolism and interferon-stimulated genes. Acute and prolonged ACTH exposure engage distinct transcriptional programmes. Acute stimulation activates immediate-early genes and stress responses, while prolonged exposure suppresses mitochondrial gene expression through transcriptional dampening mechanisms. Dexamethasone is associated with the inhibition of cholesterol metabolism via SREBP pathway suppression. These findings illuminate HPA axis adaptation and glucocorticoid-induced adrenal suppression.<\/jats:p>","DOI":"10.3390\/cimb48020135","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T09:05:27Z","timestamp":1769504727000},"page":"135","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Effects of ACTH and Dexamethasone on the Transcriptomic Profile of the Rat Adrenal Gland: An In Vivo Study"],"prefix":"10.3390","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-3394-5336","authenticated-orcid":false,"given":"Emilia","family":"Cicha","sequence":"first","affiliation":[{"name":"Animal Facility, Poznan University of Medical Sciences, Rokietnicka 8, 60-806 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5506-2397","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"Blatkiewicz","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Poznan University of Medical Sciences, 60-781 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7399-0303","authenticated-orcid":false,"given":"Karol","family":"Jopek","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Poznan University of Medical Sciences, 60-781 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0150-3665","authenticated-orcid":false,"given":"Marta","family":"Szyszka","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Poznan University of Medical Sciences, 60-781 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr W.","family":"Malendowicz","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Poznan University of Medical Sciences, 60-781 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6043-5637","authenticated-orcid":false,"given":"Anna","family":"Olechnowicz","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Poznan University of Medical Sciences, 60-781 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludwik K.","family":"Malendowicz","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Poznan University of Medical Sciences, 60-781 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2525-5777","authenticated-orcid":false,"given":"Marcin","family":"Rucinski","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Poznan University of Medical Sciences, 60-781 Poznan, Poland"},{"name":"Department of Bioinformatics and Computational Biology, Poznan University of Medical Sciences, Swiecickiego 6, 60-781 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1126\/science.6267699","article-title":"Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin","volume":"213","author":"Vale","year":"1981","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1006\/frne.1994.1013","article-title":"Regulation of pituitary ACTH secretion during chronic stress","volume":"15","author":"Aguilera","year":"1994","journal-title":"Front. 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