1. Parathyroid hormone (PTH) -fibroblast growth factor 23 (FGF23) feedback loop.
Parathyroid hormone (PTH) -fibroblast growth factor 23 (FGF23) feedback loop. PTH binds to the parathyroid hormone receptor (PTH1R) on osteocytes and osteoblasts and activates protein kinase A (PKA), which increases nuclear receptor–associated protein 1 (Nurr1) expression. Nurr1 then binds to defined nerve growth factor-induced clone B response elements in the FGF23 promoter and induces FGF23 transcription. FGF23, in turn, inhibits PTH production. In CKD, however, hyperparathyroidism increases Nurr1 and FGF23 expression, but downregulation of the FGF23 receptor complex (Klotho-fibroblastic growth receptor 1 [FGFR1]) makes the parathyroid gland (PTG) and kidney resistant to the actions of FGF23. Calcimimetics decrease PTH, Nurr1, and FGF23. Modified from reference 36, with permission.
Cynthia S. Ritter, and Eduardo Slatopolsky CJASN 2016;11:
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