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Stressors significantly impact gene expression along the HPA axis and in hypothalamic nuclei that drive it, including the paraventricular nucleus (PVN). To identify genetic regulators of stress responses in the PVN, adult mice underwent 2\u2009h of multi\u2010modal stress before gene expression profiles were analyzed using bulk RNA sequencing. A transcription factor zinc finger and BTB domain containing 16 (Zbtb16), also known as PLZF, was identified as a stress responsive, glucocorticoid receptor (GR) target in the PVN. Zbtb16 mRNA expression was increased by two\u2010fold in male and female mice within 2\u2009h of restraint stress or injection of a synthetic glucocorticoid, dexamethasone (DEX). Immunohistochemistry (IHC) confirmed Zbtb16 protein expression and localization in the PVN following 20\u2009min of restraint stress and 4\u2009h of recovery. Cellular analyses revealed that Zbtb16 was highly expressed in CRH neurons in the PVN, neurons routinely activated post\u2010stress as indicated by colocalization with c\u2010FOS. Adult mice were also exposed to an immune stress by injection of tumor necrosis factor alpha (TNF\u03b1) to assess Zbtb16 regulation. Expanded analyses indicated that the cell specificity of Zbtb16 expression was region\u2010specific, colocalizing with CRH neurons in the mid\u2010PVN but more in astrocytes surrounding the PVN. These findings identify Zbtb16 as a glucocorticoid\u2010 and cytokine\u2010inducible transcriptional regulator with region\u2010 and cell type\u2010specific roles in PVN stress circuitry.<\/jats:p>","DOI":"10.1111\/ejn.70454","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T10:53:09Z","timestamp":1773312789000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Region and Cell\u2010Selective Induction of Zbtb16\/Plzf by Multiple Stressors in the Adult Murine Hypothalamus"],"prefix":"10.1111","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5632-0466","authenticated-orcid":false,"given":"Mina","family":"Roueinfar","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences Colorado State University  Fort Collins Colorado 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