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As nesfatin\u20101 neurons co\u2010localized with TRH and GnRH neurons in the hypothalamus, it could play a role in centrally hypothyroidism induced testicular dysfunction. Selenium (Se), by affecting thyroid iodide supply, could relieve these disturbances. So, we aim to identify the role of nesfatin\u20101 as a link between testicular dysfunction and hypothyroidism through modulating the MAPK\/ERK pathway while discussing the possible role of Se in alleviating hypothyroidism and associated testicular damage. Forty male rats were divided equally into: Control: distilled water, Se: Se orally, Propylthiouracil (PTU): PTU orally, PTU\u2009+\u2009Se: Se with PTU orally. Serum thyroid function, gonadal hormones, nesfatin\u20101, testicular redox status, sperm analysis, brain tissue GnRH, nucleobindin 2\u2010derived polypeptide, pMAPK\/ERK gene expression, histological changes and immunohistochemical expression of testicular proliferating cell antigen (PCNA) were done. PTU induced hypothyroidism and reduction of gonadal hormones which both were correlated with reduced nesfatin\u20101. There was testicular stress with reduced GnRH, NUCB2, pMAPK\/ERK gene expression, and PCNA immunopositive cells. These parameters were reversed by Se. Nesfatin\u20101 could be the central link between hypothyroidism and disturbances of the hypothalamic pituitary testicular axis.<\/jats:p>","DOI":"10.14814\/phy2.15923","type":"journal-article","created":{"date-parts":[[2024,1,25]],"date-time":"2024-01-25T05:30:20Z","timestamp":1706160620000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Selenium protects against nesfatin\u20101 modulation of the hypothalamic\u2010pituitary\u2010testicular axis during hypothyroidism in male rats"],"prefix":"10.14814","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8564-0722","authenticated-orcid":false,"given":"Rehab Ahmed Ahmed","family":"El\u2010Shaer","sequence":"first","affiliation":[{"name":"Medical Physiology Department, Faculty of Medicine Tanta University  Tanta 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