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However, its peripheral function in epididymis was still elusive.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>The purpose of this study was to determine the pro\u2010secretion effect of leptin on the rat epididymal epithelium.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>In the present study, real\u2010time quantitative polymerase chain reaction, western blot, and immunohistochemical analysis were employed to detect the expression pattern of leptin receptors in rat epididymis. The pro\u2010secretion effect of leptin on epididymal epithelial cells was measured by short\u2010circuit current, and the prostaglandin E<jats:sub>2<\/jats:sub> and cyclic adenosine monophosphate level was evaluated by enzyme\u2010linked immunosorbent assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We verified that the leptin receptor was located on the epididymal epithelium, with a relatively high expression level in corpus and cauda epididymis. Ussing chamber experiments showed that leptin stimulated a significant rise of the short\u2010circuit current in rat epididymal epithelial cells, which could be abolished by the specific leptin receptor antagonist peptide Allo\u2010aca, or by removing the ambient Cl<jats:sup>\u2212<\/jats:sup> and HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>. Furthermore, the leptin\u2010stimulated short\u2010circuit current response could be abrogated by blocking the apical cystic fibrosis transmembrane regulator or the basolateral Na<jats:sup>+<\/jats:sup>\u2010K<jats:sup>+<\/jats:sup>\u20102Cl<jats:sup>\u2212<\/jats:sup> cotransporter. Our pharmacological experiments manifested that interfering with the prostaglandin H synthase\u20102\u2010prostaglandin E2\u2010EP2\/EP4\u2010adenylate cyclase pathways could significantly blunt the cystic fibrosis transmembrane regulator\u2010mediated anion secretion induced by leptin. The enzyme\u2010linked immunosorbent assay demonstrated that leptin could induce a substantial increase in prostaglandin E<jats:sub>2<\/jats:sub> release and cyclic adenosine monophosphate synthesis of primary cultured rat cauda epididymal epithelial cells. Our data also suggested that JAK2, ERK, and <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.medchemexpress.cn\/Targets\/PI3K.html\">PI3K<\/jats:ext-link>\u2010dependent phosphorylation may be involved in the activation of prostaglandin H synthase\u20102 and the subsequent prostaglandin E<jats:sub>2<\/jats:sub> production.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The present study demonstrated the pro\u2010secretion function of leptin in rat epididymal epithelium via the activation of cystic fibrosis transmembrane regulator and Na<jats:sup>+<\/jats:sup>\u2010K<jats:sup>+<\/jats:sup>\u20102Cl<jats:sup>\u2212<\/jats:sup> cotransporter, which was dependent on the paracrine\/autocrine prostaglandin E<jats:sub>2<\/jats:sub> stimulated EP2\/EP4\u2010adenylate cyclase pathways, and thus contributed to the formation of an appropriate microenvironment essential for sperm maturation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/andr.13656","type":"journal-article","created":{"date-parts":[[2024,5,23]],"date-time":"2024-05-23T06:23:41Z","timestamp":1716445421000},"page":"371-381","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cellular mechanism underlying leptin\u2010induced anion secretion of rat epididymal epithelial cells"],"prefix":"10.1111","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8299-2730","authenticated-orcid":false,"given":"Dong\u2010Dong","family":"Gao","sequence":"first","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Physical Activity and Health Promotion Scientific Research Center Guangzhou Sport University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guo\u2010Qing","family":"Liu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Physical Activity and Health 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