PF-04691502 in a 2-fold increase in 24OHase mRNA compared to LC . Cinacalcet increased expression of 24OHase mRNA 3-fold compared to NC control . FGF-23 or cAMP treatment had no effect on expression of 24OHase . Effect of the calcimimetic cinacalcet on 1 OHase and PTH mRNA in human parathyroid cells. Parathyroid cell monolayers from patients with secondary hyperparathyroidism were treated for 24 h with NC medium with or without cinacalcet . Cinacalcet treatment resulted in a 42% increase in 1 OHase mRNA , and a 53% decrease in PTH mRNA . Results reported as average SEM, percent of NC values . 78 C.S. Ritter et al. / Journal of Steroid Biochemistry & Molecular Biology 73–80 pancreas, skin, lymph nodes, monocytes, adrenal, prostate, placenta, ovary, brain, bone, and parathyroid glands .
The importance of the 1 OHase in the parathyroid glands was demonstrated in the recent Ergosterol report of Cheng et al. that found that parathyroid-speciﬁc knockout of the 1 OHase in mice produced a 4-fold increase in basal PTH levels . Under normal conditions, extrarenal production of calcitriol does not affect circulating levels of the hormone, but rather carries out specialized, noncalcitropic functions, and is regulated in an autocrine/paracrine cell-speciﬁc manner . The presence of the 1 OHase in the parathyroid glands, and the importance of these glands in mineral homeostasis, raises questions purchase TAK-875 about the factors that may regulate its expression and activity. The renal 1 OHase is known to be induced by low dietary calcium via increased PTH/cAMP and suppressed by high dietary phosphate , possibly via FGF-23 . In our studies, Regulation of 24OHase mRNA in human parathyroid cells. Parathyroid cell cAMP directly induced the 1 OHase in parathyroid cell cultures. monolayers from patients with secondary hyperparathyroidism were treated for Thus, the downstream pathways from cAMP appear to be similar 24 h with HC or 1 M cinacalcet .
Increases of 2- in renal proximal tubular cells and parathyroid cells. and 3-fold in 24OHase expression were seen after HC or cinacalcet treatment, respectively. Results reported as order chloroxine average SEM, percent of control values . On the other hand, we found that FGF-23, a potent and rapid inhibitor of 1 OHase in the kidney had the opposite effect in cultured human parathyroid cells. This conﬁrms previous results Regulation of 1 ˛ OHase activity in human parathyroid cells by Krajisnik et al. , who found that FGF-23 increased 1 OHase in primary cultures of bovine parathyroid cells.
Serum levels of by calcium FGF-23 are markedly increased in advanced stages of chronic kid- ney disease, most likely due to chronic hyperphosphatemia and/or To conﬁrm that increased 1 OHase mRNA results in increased impared renal excretion of the protein. Therefore, consistently high activity, we examined the ability of 1 OHase to 1 -hydroxylate levels of FGF-23 may contribute to the increased expression of 25D 3 under high calcium conditions in human parathyroid parathyroid .