{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T05:50:51Z","timestamp":1787637051293,"version":"build-2736575974"},"reference-count":122,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T00:00:00Z","timestamp":1756944000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2014Next Generation EU, Mission 4 Component 1","award":["CUP G53D23005000006"],"award-info":[{"award-number":["CUP G53D23005000006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cushing\u2019s disease (CD) is a rare neuroendocrine disorder caused by ACTH-secreting pituitary adenomas, presenting significant diagnostic and therapeutic challenges. Given the evolutionary conservation of the hypothalamic\u2013pituitary\u2013adrenal axis, this review explores the translational value of spontaneous CD forms in dogs, horses, cats, small mammals, and rats, as well as of experimental models in mice, rats, and zebrafish. Dogs are the most studied, showing strong molecular and clinical similarities with human CD, making them valuable for preclinical drug and diagnostic research. While equine and feline CD are less characterized, they may provide insights into dopaminergic therapies and glucocorticoid resistance. Nevertheless, practical and ethical challenges limit the experimental use of companion animals. In preclinical research, mouse models are widely used to study hypercortisolism and test therapeutic agents via transgenic and xenograft strategies. Conversely, few studies are available on a zebrafish transgenic model for CD, displaying pituitary corticotroph expansion and partial resistance to glucocorticoid-negative feedback at the larval stage, while adults exhibit hypercortisolism resembling the human phenotype. Future transplantable systems in zebrafish may overcome several limitations observed in mice, supporting CD research. Collectively, these animal models, each offering unique advantages and limitations, provide a diverse toolkit for advancing CD research and improving human clinical outcomes.<\/jats:p>","DOI":"10.3390\/ijms26178626","type":"journal-article","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T07:46:17Z","timestamp":1757058377000},"page":"8626","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cushing\u2019s Disease in the Animal Kingdom: Translational Insights for Human Medicine"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7909-4289","authenticated-orcid":false,"given":"Elena","family":"Massardi","sequence":"first","affiliation":[{"name":"Department of Medical Biotechnology and Translational Medicine, University of Milan, 20129 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Germano","family":"Gaudenzi","sequence":"additional","affiliation":[{"name":"Laboratory of Geriatric and Oncologic Neuroendocrinology Research, IRCCS, Istituto Auxologico Italiano, Cusano Milanino, 20095 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9321-9508","authenticated-orcid":false,"given":"Silvia","family":"Carra","sequence":"additional","affiliation":[{"name":"Laboratory of Endocrine and Metabolic Research, IRCCS, Istituto Auxologico Italiano, Cusano Milanino, 20095 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Oldani","sequence":"additional","affiliation":[{"name":"Laboratory of Geriatric and Oncologic Neuroendocrinology Research, IRCCS, Istituto Auxologico Italiano, Cusano Milanino, 20095 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilona","family":"Rybinska","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology and Translational Medicine, University of Milan, 20129 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2068-9581","authenticated-orcid":false,"given":"Luca","family":"Persani","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology and Translational Medicine, University of Milan, 20129 Milan, Italy"},{"name":"Laboratory of Endocrine and Metabolic Research, IRCCS, Istituto Auxologico Italiano, Cusano Milanino, 20095 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2478-683X","authenticated-orcid":false,"given":"Giovanni","family":"Vitale","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology and Translational Medicine, University of Milan, 20129 Milan, Italy"},{"name":"Laboratory of Geriatric and Oncologic Neuroendocrinology Research, IRCCS, Istituto Auxologico Italiano, Cusano Milanino, 20095 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1007\/s12020-016-0984-8","article-title":"Cushing\u2019s disease: The burden of illness","volume":"56","author":"Pivonello","year":"2017","journal-title":"Endocrine"},{"key":"ref_2","first-page":"140","article-title":"Cushing\u2019s disease in dogs and humans","volume":"71","author":"Meij","year":"2009","journal-title":"Horm. 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