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The parathyroid is a target organ for FGF23 in rats
Iddo Z. Ben-Dov, … , Tally Naveh-Many, Justin Silver
Iddo Z. Ben-Dov, … , Tally Naveh-Many, Justin Silver
Published December 3, 2007; First published November 8, 2007
Citation Information: J Clin Invest. 2007;117(12):4003-4008. https://doi.org/10.1172/JCI32409.
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Categories: Research Article Nephrology

The parathyroid is a target organ for FGF23 in rats

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Abstract

Phosphate homeostasis is maintained by a counterbalance between efflux from the kidney and influx from intestine and bone. FGF23 is a bone-derived phosphaturic hormone that acts on the kidney to increase phosphate excretion and suppress biosynthesis of vitamin D. FGF23 signals with highest efficacy through several FGF receptors (FGFRs) bound by the transmembrane protein Klotho as a coreceptor. Since most tissues express FGFR, expression of Klotho determines FGF23 target organs. Here we identify the parathyroid as a target organ for FGF23 in rats. We show that the parathyroid gland expressed Klotho and 2 FGFRs. The administration of recombinant FGF23 led to an increase in parathyroid Klotho levels. In addition, FGF23 activated the MAPK pathway in the parathyroid through ERK1/2 phosphorylation and increased early growth response 1 mRNA levels. Using both rats and in vitro rat parathyroid cultures, we show that FGF23 suppressed both parathyroid hormone (PTH) secretion and PTH gene expression. The FGF23-induced decrease in PTH secretion was prevented by a MAPK inhibitor. These data indicate that FGF23 acts directly on the parathyroid through the MAPK pathway to decrease serum PTH. This bone-parathyroid endocrine axis adds a new dimension to the understanding of mineral homeostasis.

Authors

Iddo Z. Ben-Dov, Hillel Galitzer, Vardit Lavi-Moshayoff, Regina Goetz, Makoto Kuro-o, Moosa Mohammadi, Roy Sirkis, Tally Naveh-Many, Justin Silver

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Figure 3

FGF23 decreases serum PTH and PTH mRNA levels in vivo in short-term experiments.

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FGF23 decreases serum PTH and PTH mRNA levels in vivo in short-term expe...
FGF23R176Q/R179Q, FGF23core, FGF23 wild-type (FGF23wt), or HEPES were injected i.v. or i.p. into 4 rats per group. At the indicated times, serum PTH levels were measured and parathyroids extracted for RNA analysis. (A) Serum PTH levels at 10 and 30 minutes after i.v. FGF23R176Q/R179Q or HEPES administration. (B) Serum PTH levels from untreated rats (control) and rats 20 or 40 minutes after i.p. FGF23R176Q/R179Q or FGF23core treatment. (C) Serum PTH at 24 hours after i.p. HEPES, FGF23R176Q/R179Q, or FGF23wt administration. (D) qRT-PCR analysis for PTH mRNA of RNA extracted from microdissected parathyroids 40 minutes after FGF23R176Q/R179Q or FGF23core treatment. FGF23R176Q/R179Q and FGF23wt administration decreased serum PTH and PTH mRNA levels. *P < 0.05 compared with FGF23core and (where applicable) controls.
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