{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T09:34:31Z","timestamp":1792402471999,"version":"4.4.0"},"reference-count":104,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T00:00:00Z","timestamp":1636675200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This review addresses the molecular mechanisms of corticotropin-releasing factor (CRF) regulation in the hypothalamus under stress and stress resilience. CRF in the hypothalamus plays a central role in regulating the stress response. CRF stimulates adrenocorticotropic hormone (ACTH) release from the anterior pituitary. ACTH stimulates glucocorticoid secretion from the adrenal glands. Glucocorticoids are essential for stress coping, stress resilience, and homeostasis. The activated hypothalamic-pituitary-adrenal axis is suppressed by the negative feedback from glucocorticoids. Glucocorticoid-dependent repression of cAMP-stimulated Crf promoter activity is mediated by both the negative glucocorticoid response element and the serum response element. Conversely, the inducible cAMP-early repressor can suppress the stress response via inhibition of the cAMP-dependent Crf gene, as can the suppressor of cytokine signaling-3 in the hypothalamus. CRF receptor type 1 is mainly involved in a stress response, depression, anorexia, and seizure, while CRF receptor type 2 mediates \u201cstress coping\u201d mechanisms such as anxiolysis in the brain. Differential effects of FK506-binding immunophilins, FKBP4 and FKBP5, contribute to the efficiency of glucocorticoids under stress resilience. Together, a variety of factors contribute to stress resilience. All these factors would have the differential roles under stress resilience.<\/jats:p>","DOI":"10.3390\/ijms222212242","type":"journal-article","created":{"date-parts":[[2021,11,14]],"date-time":"2021-11-14T20:48:36Z","timestamp":1636922916000},"page":"12242","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":107,"title":["Hypothalamic Regulation of Corticotropin-Releasing Factor under Stress and Stress Resilience"],"prefix":"10.3390","volume":"22","author":[{"given":"Kazunori","family":"Kageyama","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Aomori, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasumasa","family":"Iwasaki","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition Management Nutrition Course, Faculty of Health Science, Suzuka University of Medical Science, 1001-1 Kishioka-cho, Suzuka 510-0293, Mie, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3775-1719","authenticated-orcid":false,"given":"Makoto","family":"Daimon","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Aomori, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.bbr.2014.12.047","article-title":"A systems approach to stress, stressors and resilience in humans","volume":"282","author":"Oken","year":"2015","journal-title":"Behav. 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