{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:09:12Z","timestamp":1785409752492,"version":"3.56.0"},"posted":{"date-parts":[[2026,6,19]]},"group-title":"Neuroscience","reference-count":54,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:00:00Z","timestamp":1781827200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"University of Michigan Eisenberg Family Depression Center Oscar Stern Award to NCT"},{"name":"University of Michigan LSA-OVPR funds to NCT"},{"award":["F31 HD114532 to KMS"],"award-info":[{"award-number":["F31 HD114532 to KMS"]}],"id":[{"id":"https:\/\/ror.org\/04byxyr05","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["U2CDK135066 (MMPC-LIVE)"],"award-info":[{"award-number":["U2CDK135066 (MMPC-LIVE)"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["DK020572 (MDRC)"],"award-info":[{"award-number":["DK020572 (MDRC)"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["DK089503 (MNORC)"],"award-info":[{"award-number":["DK089503 (MNORC)"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Combined oral contraceptives (OCs), containing synthetic estrogen and a progestin such as levonorgestrel (LVNG), are widely used, and up to 10% of users experience adverse mood states and increased depression risk. It is well-established that OCs modulate the hypothalamic-pituitary-adrenal (HPA) axis and blunt the cortisol responses to acute stress. This interaction with stress regulatory pathways is one mechanism by which OCs might impact mood. Here, we used a mouse model of OC exposure (ethinyl estradiol (EE) + LVNG) to investigate how OCs affect regulation of the diurnal CORT cycle and stress-related signaling in the dorsal and ventral hippocampus and paraventricular nucleus of the hypothalamus (PVN). We found that EE+LVNG did not alter basal corticosterone (CORT) levels, but impaired glucocorticoid receptor (GR) - mediated negative feedback in the dexamethasone suppression test. Molecular analyses revealed distinct, region-specific effects. In the dorsal hippocampus, EE+LVNG enhanced glucocorticoid receptor (GR)-dependent gene signaling and prolonged\n                  <jats:italic>Fkbp5<\/jats:italic>\n                  induction. In the ventral hippocampus, EE+LVNG enhanced mineralocorticoid receptor (MR)-dependent signaling and reduced stress-induced corticotropin-releasing factor expression. In the PVN, EE+LVNG reduced\n                  <jats:italic>MR<\/jats:italic>\n                  expression and modulated MR-dependent signaling. Together, these findings demonstrate that chronic OC exposure disrupts GR- and MR-dependent regulation across stress-related brain regions and impairs glucocorticoid feedback, providing potential mechanisms by which OCs blunt stress responsivity, modify long-term HPA-axis function, and increase susceptibility or resilience to stress and depression.\n                <\/jats:p>","DOI":"10.64898\/2026.06.15.731933","type":"posted-content","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T22:15:16Z","timestamp":1781907316000},"source":"Crossref","is-referenced-by-count":0,"title":["Region-specific regulation of glucocorticoid and mineralocorticoid receptor signaling in a mouse model of oral contraceptive exposure"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9327-1843","authenticated-orcid":false,"given":"Kristen M.","family":"Schuh","sequence":"first","affiliation":[{"name":"Psychology Department, University of Michigan, Ann Arbor MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mackenzie G.","family":"Woock","sequence":"additional","affiliation":[{"name":"Psychology Department, University of Michigan, Ann Arbor MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan J.","family":"Vaandrager","sequence":"additional","affiliation":[{"name":"Psychology Department, University of Michigan, Ann Arbor MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth G.","family":"Romano","sequence":"additional","affiliation":[{"name":"Psychology Department, University of Michigan, Ann Arbor MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutong","family":"He","sequence":"additional","affiliation":[{"name":"Psychology Department, University of Michigan, Ann Arbor MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniella","family":"Ludmir","sequence":"additional","affiliation":[{"name":"Psychology Department, University of Michigan, Ann Arbor MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5676-1579","authenticated-orcid":false,"given":"Natalie C.","family":"Tronson","sequence":"additional","affiliation":[{"name":"Psychology Department, University of Michigan, Ann Arbor MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026062217301930000_2026.06.15.731933v1.1","doi-asserted-by":"crossref","first-page":"e45030","DOI":"10.2196\/45030","article-title":"Contraceptive Use Measured in a National Population\u2013Based Approach: Cross-Sectional Study of Administrative Versus Survey Data","volume":"10","year":"2024","journal-title":"JMIR Public Health Surveill"},{"key":"2026062217301930000_2026.06.15.731933v1.2","doi-asserted-by":"publisher","DOI":"10.3275\/8971"},{"key":"2026062217301930000_2026.06.15.731933v1.3","first-page":"1","article-title":"Evidence for Stress-like Alterations in the HPA-Axis in Women Taking Oral Contraceptives","volume":"7","year":"2017","journal-title":"Scientific Reports"},{"key":"2026062217301930000_2026.06.15.731933v1.4","doi-asserted-by":"publisher","DOI":"10.1097\/00006842-199903000-00006"},{"key":"2026062217301930000_2026.06.15.731933v1.5","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23904"},{"key":"2026062217301930000_2026.06.15.731933v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsycho.2012.10.007"},{"key":"2026062217301930000_2026.06.15.731933v1.7","doi-asserted-by":"publisher","DOI":"10.1037\/a0036687"},{"key":"2026062217301930000_2026.06.15.731933v1.8","doi-asserted-by":"crossref","unstructured":"Schuh KM , Ahmed J , Kwak E , Xu CX , Davis TT , Aronoff CB , et al. A mouse model of oral contraceptive exposure: Depression, motivation, and the stress response. Horm Behav. 2024;158:105470.","DOI":"10.1016\/j.yhbeh.2023.105470"},{"key":"2026062217301930000_2026.06.15.731933v1.9","doi-asserted-by":"crossref","unstructured":"Tronson NC , Schuh KM . Hormonal contraceptives, stress, and the brain: The critical need for animal models. 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Ethinyl estradiol and levonorgestrel coadministration induces hypophagia and increases energy expenditure in female rats. Endocrinology. 2026:bqag064.","DOI":"10.1210\/endocr\/bqag064"},{"key":"2026062217301930000_2026.06.15.731933v1.37","doi-asserted-by":"crossref","unstructured":"Lacasse JM , Fletcher BC , Murray SH , Pasetto-Patrick M , Sheehan AC , Trujano C , et al. Contraceptive hormones and social instability stress in adolescence and in adulthood: Effects on anxiety and social behaviour. 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Hormonal contraceptives modulate resilience to psychiatric and neurodegenerative disease. Horm Behav. 2025;176:105823.","DOI":"10.1016\/j.yhbeh.2025.105823"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.06.15.731933","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:30:39Z","timestamp":1782174639000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.06.15.731933"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,19]]},"references-count":54,"URL":"https:\/\/doi.org\/10.64898\/2026.06.15.731933","relation":{},"subject":[],"published":{"date-parts":[[2026,6,19]]},"subtype":"preprint"}}