FGF23 and the Parathyroid
Klotho and fibroblast growth factor 1 (FGFR1) are expressed not only in FGF23’s classical target organ, the kidney, but also in other organs such as the parathyroid. FGF23 acts on the parathyroid to decrease PTH mRNA and serum PTH levels. It does this by activating the MAPK pathway. In chronic kidney disease there are very high levels of serum FGF23 together with increased serum PTH levels, implying resistance of the parathyroid to the action of FGF23. This has been shown in parathyroid tissue surgically removed from dialysis patients as well as in experimental models of uremia to be due to down-regulation of klotho-FGFR1 expression in the parathyroid. Moreover, the parathyroids of rats with advanced uremia do not respond to administered FGF23 by activation of the MAPK pathway or inhibition of PTH secretion. Therefore, there is down-regulation of parathyroid klotho-FGFR1 in CKD which correlates with the resistance of the parathyroid to FGF23. A further subject of great interest in this field is the effect of PTH to directly increase FGF23 expression by osteoblast like cells in culture and the observations that parathyroidectomy prevents and corrects the increased serum FGF23 level of experimental CKD as well as decreases FGF23 in patients with CKD. There is therefore a negative feedback loop between bone and the parathyroid.
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