Bone Abstracts

As a bone-derived hormone that regulates phosphate homeostasis and renal 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃] production, fibroblast growth factor (FGF)-23 has been postulated to indirectly control calcium and bone metabolism by modulating the levels of phosphate and 1,25(OH)₂D₃. However, the presence of FGF receptor-1 (FGFR-1) proteins in the intestinal epithelial cells suggests that the intestine may directly respond to FGF-23. The present study, therefore, aimed to investigate the local production of FGF-23 as well as its paracrine actions in the intestine. The expression of FGF-23 proteins in the rat small and large intestine was determined by quantitative immunohistochemistry. In early lactating rats with high calcium demand for lactogenesis (day 8 of lactation), the FGF-23 levels in the duodenum and cecum were found to markedly increase. This phenomenon was hypothesized to prevent excessive calcium absorption. In addition, the lactation-induced upregulation of intestinal FGF-23 expression was diminished by 7-day s.c. injection of bromocriptine, a potent inhibitor of pituitary release of prolactin that is one of the calcium-regulating hormones during lactation. Similar findings were also observed in late lactating rats (day 21 of lactation). An in vitro radioactive calcium flux study in intestinal epithelium-like Caco-2 monolayers showed that FGF-23 was capable of inhibiting the prolactin-enhanced transepithelial calcium transport. Our results thus corroborate the possible paracrine effects of FGF-23 in the rat intestine, especially during lactation, which may help counterbalance the actions of calciotropic hormones, and prevent excessive calcium absorption.