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Theca cells are present in the outer layer of follicles, providing communication with the pituitary axis through the established vascular system around the follicle. As LH target cells, it is unknown whether theca cells can produce AREG after LH stimulation.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Primary cultured human theca cells were treated with LH (with or without the inhibitor of PKA, H89), or agonists of adenylate cyclase (forskolin or db-cAMP). The mRNA and protein levels of <jats:italic>AREG<\/jats:italic> were evaluated by RT-qPCR, immunochemistry, immunofluorescence, western blotting, and ELISA.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Immunohistochemistry of normal ovarian tissue obtained in the early-mid follicle phase showed that <jats:italic>AREG<\/jats:italic> expression was absent in both the theca layer and the granulosa cell layer of antral follicles. Double immunofluorescent staining revealed colocalization of AREG and CYP17A1 in human theca cells and colocalization of FSHR and AREG in human granulosa cells isolated from follicular fluid collected during IVF\/ICSI after hCG trigger. LH significantly increased the mRNA and protein levels of <jats:italic>AREG<\/jats:italic> in human theca cells and the concentration of AREG in the culture medium. Forskolin and db-cAMP, activators of the cAMP\/PKA signalling pathway, also significantly increased the mRNA and protein levels of <jats:italic>AREG<\/jats:italic> in human theca cells and the concentration of AREG in the culture medium. H89 antagonized the stimulating effect of LH on <jats:italic>AREG<\/jats:italic> expression in human theca cells. In addition, the concentration of AREG was lower in polycystic ovarian syndrome (PCOS) follicular fluid than in normal follicular fluid. The mRNA levels of <jats:italic>AREG<\/jats:italic> were significantly lower in PCOS granulosa cells and theca cells than in normal granulosa cells and theca cells.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>LH can stimulate the expression of <jats:italic>AREG<\/jats:italic> in human theca cells, and the adenylate cyclase\/cAMP\/PKA cascade may mediate this process. Expression of <jats:italic>AREG<\/jats:italic> is decreased in PCOS theca cells compared to normal theca cells, with or without LH stimulation.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13048-022-01062-5","type":"journal-article","created":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T15:03:42Z","timestamp":1670425422000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Luteinizing hormone stimulates the expression of amphiregulin in human theca cells"],"prefix":"10.1186","volume":"15","author":[{"given":"Yang","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiping","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoting","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xi","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rihan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Turui","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minghui","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,12,7]]},"reference":[{"issue":"1","key":"1062_CR1","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1095\/biolreprod.113.116814","volume":"91","author":"X Liu","year":"2014","unstructured":"Liu X, Xie F, Zamah AM, Cao B, Conti M. 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