FGF-23 requires the protein cells from one patient. Monolayers were treated for 24 h with Klotho as co-receptor for high afﬁnity binding to FGF receptors . serum-free LC or HC in the presence of nM 25D 3 . Medium While binding of FGF-23 to the FGFR/Klotho complex activates the was collected and measured for 1, indicating that ther investigation. The phenformin physiologic explanation for the stimulation of the parathyroid 1 OHase by FGF-23 in parathyroid cells is not known, but it may contribute to the reported suppression of PTH by FGF-23 .
The ﬁnding that no suppression of PTH mRNA was seen in the present study could be Magnolol explained by the recent demonstration of a In addition to being expressed in the kidney, the 1 OHase is resistance to FGF-23 in parathyroid glands of patients and rats with found in a wide variety of tissues including colon, breast tissue, chronic kidney failure due to decreased FGFR/Klotho expression and signaling . In cultured human parathyroid cells, we found that high calcium, as well as the calcium receptor activator cinacalcet, had a direct stimulatory effect on 1 OHase expression, which is opposite to the direct effect of calcium on the 1 OHase in renal proximal tubular cells . We also found that high calcium directly increased the activity of the 1 OHase protein in human parathyroid cell, as purchase ARRY-520 evidenced by 1 -hydroxylation of 25D 3 in human parathy- roid cultures.
Calcium and cinacalcet treatment of parathyroid cultures also resulted in an increased expression of the 24OHase. It is not known if this is a direct effect of calcium, or the result of an increased local production of calcitriol, which in turn induces expression of the 24OHase. It is not unexpected that regulation of the parathyroid 1 OHase by calcium would differ from that of the renal enzyme. Suppression of the renal 1 OHase by calcium is part order celestone of a feedback loop to reduce calcitriol-mediated intestinal calcium absorption. A simi Calcium induces 1-hydroxylation of 25D 3 in human parathyroid cells. lar suppression of the 1 OHase in the parathyroid glands by high Parathyroid cells monolayers from a patient with secondary hyperparathyroidism calcium would reduce endogenous calcitriol production and be were treated for 24 h with LC or HC medium containing nM of 25D 3 .
Medium was collected and measured for Results reported counterproductive to calcium feedback on PTH release. Our ﬁndings suggest that induction of the 1 OHase may be an additional, indirect mechanism for the control of PTH by calcium and calcium as average pg 1 -hydroxylated metabolites per g protein SEM, n = 6 each. receptor activators. Dietary calcium also stimulates the 1 OHase 2 Román-García et al. Severe Hyperparathyroidism nanotechnology and Dusps Endocrinology, April 2, activating the ERK/MAPK pathway in the parathyroid glands . However, in sHPT, the inhibitory effect of FGF23 on PTH synthesis is not observed . The absence of FGF23 inhibition of PTH synthesis has been recently associated with the low leveL.