Fibroblast Growth Factor (FGF) 23 Regulates the Plasma Levels of Parathyroid Hormone In Vivo Through the FGF Receptor in Normocalcemia, But Not in Hypocalcemia

Autor: Klaus Olgaard, Maria L. Mace, Eva Gravesen, Ewa Lewin, Anders Nordholm
Rok vydání: 2017
Předmět:
0301 basic medicine
Fibroblast growth factor 23
endocrine system
medicine.medical_specialty
Calcitriol
Endocrinology
Diabetes and Metabolism
030232 urology & nephrology
Parathyroid hormone
urologic and male genital diseases
Fibroblast growth factor
03 medical and health sciences
0302 clinical medicine
Endocrinology
FGF23
Internal medicine
medicine
Homeostasis
Animals
Orthopedics and Sports Medicine
Rats
Wistar
Receptor
Calcitriol/blood
Uremia
Original Research
Calcium metabolism
Hypocalcemia
FGFR
Chemistry
Homeostasis/physiology
Receptors
Fibroblast Growth Factor/metabolism
Fibroblast Growth Factors/metabolism
Parathyroid chief cell
Receptors
Fibroblast Growth Factor
PD173074
Fibroblast Growth Factors
Fibroblast Growth Factor-23
stomatognathic diseases
030104 developmental biology
medicine.anatomical_structure
Parathyroid Hormone
Parathyroid Hormone/blood
Hypocalcemia/blood
Parathyroid gland
Uremia/metabolism
hormones
hormone substitutes
and hormone antagonists
PTH
medicine.drug
Zdroj: Mace, M L, Gravesen, E, Nordholm, A, Ølgaard, K & Lewin, E 2018, ' Fibroblast Growth Factor (FGF) 23 Regulates the Plasma Levels of Parathyroid Hormone In Vivo Through the FGF Receptor in Normocalcemia, But Not in Hypocalcemia ', Calcified Tissue International, vol. 102, no. 1, pp. 85-92 . https://doi.org/10.1007/s00223-017-0333-9
Calcified Tissue International
ISSN: 1432-0827
0171-967X
DOI: 10.1007/s00223-017-0333-9
Popis: The calcium and phosphate homeostasis is regulated by a complex interplay between parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), and calcitriol. Experimental studies have demonstrated an inhibitory effect of FG23 on PTH production and secretion; the physiological role of this regulation is however not well understood. Surprisingly, in uremia, concomitantly elevated FGF23 and PTH levels are observed. The parathyroid gland rapidly loses its responsiveness to extracellular calcium in vitro and a functional parathyroid cell line has currently not been established. Therefore, the aim of the present investigation was to study the impact of FGF23 on the Ca2+/PTH relationship in vivo under conditions of normocalcemia and hypocalcemia. Wistar rats were allocated to treatment with intravenous recombinant FGF23 and inhibition of the FGF receptor in the setting of normocalcemia and acute hypocalcemia. We demonstrated that FGF23 rapidly inhibited PTH secretion and that this effect was completely blocked by inhibition of the FGF receptor. Furthermore, inhibition of the FGF receptor by itself significantly increased PTH levels, indicating that FGF23 has a suppressive tonus on the parathyroid gland's PTH secretion. In acute hypocalcemia, there was no effect of either recombinant FGF23 or FGF receptor inhibition on the physiological response to the low ionized calcium levels. In conclusion, FGF23 has an inhibitory tonus on PTH secretion in normocalcemia and signals through the FGF receptor. In acute hypocalcemia, when increased PTH secretion is needed to restore the calcium homeostasis, this inhibitory effect of FGF23 is abolished.
Databáze: OpenAIRE
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