title: Direct and indirect effects of parathyroid hormone on circulating levels of fibroblast growth factor 23 in vivo.
abstract: Fibroblastic growth factor 23 (FGF23) is a bone-derived hormone that has a pivotal role in the pathogenesis of mineral disorders in chronic kidney disease. To study the effect of parathyroid hormone (PTH) on FGF23, rats were parathyroidectomized for a week and then implanted with constant-delivery infusion pumps to provide vehicle, a physiological, or a threefold supraphysiological dose of parathyroid hormone. Parathyroidectomy resulted in a significant decrease in blood ionized calcium, FGF23, and calcitriol along with an increase in phosphorus concentrations. PTH replacement produced a dose-dependent increase in ionized calcium and FGF23 with decreased phosphorus. Calcitriol was also increased but there was no dose effect of PTH treatment. To maintain normal plasma calcitriol levels, two additional groups of parathyroidectomized rats were given calcitriol and temporarily treated with vehicle or the supraphysiological dose of PTH. FGF23 was significantly increased by calcitriol in the vehicle-treated rats but was not further increased above that in rats given the supraphysiological dose of PTH in the absence of calcitriol. Klotho expression in the kidney decreased after parathyroidectomy but was restored by hormone supplementation. Hence, our results show a direct and an indirect effect of PTH on FGF23 secretion, the latter through changes in calcitriol concentrations.
authors.affiliation: Department of Medicina y Cirugia Animal, Universidad de Cordoba, and Unidad de Investigacion, Servicio de Nefrología (Red in Ren), Hospital Universitario Reina Sofia (IMIBIC), Cordoba, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: López
authors.forename: M Encarnación
authors.initials: ME
authors.lastname: Rodríguez-Ortiz
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Almadén
authors.forename: Fátima
authors.initials: F
authors.lastname: Guerrero
authors.forename: A Montes
authors.initials: AM
authors.lastname: de Oca
authors.forename: Carmen
authors.initials: C
authors.lastname: Pineda
authors.forename: Vicky
authors.initials: V
authors.lastname: Shalhoub
authors.forename: Mariano
authors.initials: M
authors.lastname: Rodríguez
authors.forename: Escolástico
authors.initials: E
authors.lastname: Aguilera-Tejero
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000097:blood; D005346:Fibroblast Growth Factors / Q000097:blood / Q000187:drug effects*; D010281:Parathyroid Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D016105:Parathyroidectomy; D010758:Phosphorus / Q000097:blood; D051381:Rats
chemical_list: C505605:Fgf23 protein, rat; D010281:Parathyroid Hormone; D010758:Phosphorus; D005346:Fibroblast Growth Factors; D002117:Calcitriol; D002118:Calcium