{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:20:18Z","timestamp":1784557218864,"version":"3.55.0"},"reference-count":42,"publisher":"Bioscientifica","issue":"12","content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,12,1]]},"abstract":"<jats:p>\n                    Prolactinomas have harmful effects on human health. Bromocriptine is the only commercially available drug in China, but about 25% of prolactinoma patients do not respond to it in clinic, its pathogenesis remains unknown. Thus, its pathogenesis needs to be determined to develop new therapeutic methods for prolactinomas. The expression of ER\u03b2, TLR4, and prolactin (PRL) in the pituitary gland of C57BL\/6 mice and human prolactinoma specimen was examined by immunofluorescence or immunohistochemistry. The role of TLR4 in prolactinoma was determined using estradiol-induced models of C57BL\/6 wild-type and TLR4\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. MMQ cells were treated with estradiol, fulvestrant, and lipopolysaccharide (LPS) or transfected with TLR4 siRNA to study the expression of ER\u03b2, TLR4, and PRL in these cells. Furthermore, the interaction between ER\u03b2 and TLR4 was investigated by immunoprecipitation analysis. The expression of PRL and TLR4 was co-located and increased in the pituitary gland of mice and human prolactinoma specimen compared to that in the control specimen. Meanwhile, TLR4 knockout or treatment with the TLR4 inhibitor TAK242 not only significantly inhibited tumor overgrowth but also decreased the expression of PRL in estradiol-treated mice through p38 MAPK pathway regulation. However, MMQ treated with estradiol and LPS enhanced PRL expression than treated with estradiol or LPS alone. Finally, ER\u03b2 or TLR4 inhibition prevented the estradiol-induced PRL increase by regulating the TLR4\/p38 MAPK pathway\n                    <jats:italic>in vitro<\/jats:italic>\n                    . Estradiol promoted prolactinoma development by activating the TLR4\/p38 MAPK pathway through ER\u03b2, and TLR4 is a potential therapeutic target for prolactinoma treatment.\n                  <\/jats:p>","DOI":"10.1530\/erc-22-0168","type":"journal-article","created":{"date-parts":[[2022,10,11]],"date-time":"2022-10-11T16:59:35Z","timestamp":1665507575000},"page":"703-716","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":5,"title":["TLR4 inhibition suppresses growth in oestrogen-induced prolactinoma models"],"prefix":"10.1530","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2264-8620","authenticated-orcid":true,"given":"Yu","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Tongren hospital affiliated to Wuhan University (The Third Hospital of Wuhan), Wuhan, China"},{"name":"Department of Pharmacy, Pulmonary Hospital of Wuhan, Wuhan, China"},{"name":"Faculty of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Tongren hospital affiliated to Wuhan University (The Third Hospital of Wuhan), Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuguang","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Tongren Hospital affiliated to Wuhan University (The Third Hospital of Wuhan), Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaoyan","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Pulmonary Hospital of Wuhan, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuman","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Hubei Provincial Hospital of Integrated Traditional Chinese and Western Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Tongren hospital affiliated to Wuhan University (The Third Hospital of Wuhan), Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Ni","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Tongren hospital affiliated to Wuhan University (The Third Hospital of Wuhan), Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonggang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Tongren hospital affiliated to Wuhan University (The Third Hospital of Wuhan), Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7630-9528","authenticated-orcid":true,"given":"Jinhu","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Tongren hospital affiliated to Wuhan University (The Third Hospital of Wuhan), Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Tongren hospital affiliated to Wuhan University (The Third Hospital of Wuhan), Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Development","article-title":"Toll and toll-like receptor signalling in development","volume":"145","author":"Anthoney","year":"2018","unstructured":"Anthoney NFoldi IHidalgo A2018Toll and toll-like receptor signalling in development. 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