The parathyroid is a target organ for FGF23 in rats

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

Research output: Contribution to journalArticle

649 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)4003-4008
Number of pages6
JournalJournal of Clinical Investigation
Volume117
Issue number12
DOIs
StatePublished - Dec 2007

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Parathyroid Hormone
Fibroblast Growth Factor Receptors
Bone and Bones
Homeostasis
Phosphates
Kidney
Parathyroid Glands
Vitamin D
Intestines
Minerals
Phosphorylation
Hormones
Gene Expression
Messenger RNA
Growth
Serum

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Ben-Dov, I. Z., Galitzer, H., Lavi-Moshayoff, V., Goetz, R., Kuro-o, M., Mohammadi, M., ... Silver, J. (2007). The parathyroid is a target organ for FGF23 in rats. Journal of Clinical Investigation, 117(12), 4003-4008. https://doi.org/10.1172/JCI32409

The parathyroid is a target organ for FGF23 in rats. / Ben-Dov, Iddo Z.; Galitzer, Hillel; Lavi-Moshayoff, Vardit; Goetz, Regina; Kuro-o, Makoto; Mohammadi, Moosa; Sirkis, Roy; Naveh-Many, Tally; Silver, Justin.

In: Journal of Clinical Investigation, Vol. 117, No. 12, 12.2007, p. 4003-4008.

Research output: Contribution to journalArticle

Ben-Dov, IZ, Galitzer, H, Lavi-Moshayoff, V, Goetz, R, Kuro-o, M, Mohammadi, M, Sirkis, R, Naveh-Many, T & Silver, J 2007, 'The parathyroid is a target organ for FGF23 in rats', Journal of Clinical Investigation, vol. 117, no. 12, pp. 4003-4008. https://doi.org/10.1172/JCI32409
Ben-Dov IZ, Galitzer H, Lavi-Moshayoff V, Goetz R, Kuro-o M, Mohammadi M et al. The parathyroid is a target organ for FGF23 in rats. Journal of Clinical Investigation. 2007 Dec;117(12):4003-4008. https://doi.org/10.1172/JCI32409
Ben-Dov, Iddo Z. ; Galitzer, Hillel ; Lavi-Moshayoff, Vardit ; Goetz, Regina ; Kuro-o, Makoto ; Mohammadi, Moosa ; Sirkis, Roy ; Naveh-Many, Tally ; Silver, Justin. / The parathyroid is a target organ for FGF23 in rats. In: Journal of Clinical Investigation. 2007 ; Vol. 117, No. 12. pp. 4003-4008.
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