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Estrogen is one of the factors affecting fibroblast growth factor 23 (FGF23), a phosphorus-regulating hormone. However, the interaction between excess phosphorus and estrogen status has not been fully elucidated. This study investigated the involvement of estrogen in the effects of high phosphorus intake on bone metabolism and ectopic calcification in ovariectomized (OVX) rats. The interaction between high phosphorus diet and OVX was not observed in bone mineral density and aortic calcium. In contrast, high phosphorus intake markedly increased renal calcium concentration in sham rats, whereas the effect was attenuated in OVX rats, which was reversed by a selective estrogen-receptor modulator treatment. A strong positive correlation between renal calcium and serum FGF23 was observed. In addition, fibroblast growth factor receptor 1 (FGFR1: a predominant receptor of FGF23) inhibitor treatment partially decreased renal calcium concentrations in rats with high phosphorus intake. In conclusion, the effect of high phosphorus intake on bone metabolism and aortic calcification did not depend on the estrogen status; in contrast, high phosphorus intake synergistically induced nephrocalcinosis in the presence of estrogenic action on the bone. Furthermore, FGF23 was involved in the nephrocalcinosis induced by high phosphorus intake partially through FGFR1 signaling.<\/jats:p>","DOI":"10.1038\/s41598-020-61858-7","type":"journal-article","created":{"date-parts":[[2020,3,17]],"date-time":"2020-03-17T11:02:44Z","timestamp":1584442964000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Involvement of estrogen in phosphorus-induced nephrocalcinosis through fibroblast growth factor 23"],"prefix":"10.1038","volume":"10","author":[{"given":"Satoshi","family":"Takasugi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miho","family":"Shioyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masami","family":"Kitade","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masashi","family":"Nagata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taketo","family":"Yamaji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,3,17]]},"reference":[{"key":"61858_CR1","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1111\/sdi.12042","volume":"26","author":"MS Calvo","year":"2013","unstructured":"Calvo, M. 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