Regulation of the metabolism of 25-hydroxyvitamin D3 in primary cultures of chick kidney cells.

Abstract

A B S T R A C T A primary chick kidney cell culture is described, capable of forming 1,25-dihydroxyvitamin D3 [1,25(OH) (OH)D3). Under the latter condition, the sensitivity to bovine parathyroid hormone was enhanced, 0.04 U/ml producing a maximum response. Synthetic aminoterminal tetratriacontapeptide human parathyroid hormone was equally effective. In the absence of D metabolites, estradiol for 6 h produced a dose-dependent inhibition ofthe 1-hydroxylase, but no change in the 24-hydroxylase. Progesterone, testosterone, and corticosterone had no significant effect. In cultures grown in the presence of 25(OH)D3 no reproducible effects were obtained with either 1 ,uM estradiol or 1 ,uM testosterone, alone or in combination, but 5 ,uM corticosterone decreased the 1-and increased the 24-hydroxylase. Changes in Ca and P concentrations of the medium as well as addition of ethane-1-hydroxy-1,1-diphosphate for 48 h did not affect any of the Part of this work was presented at

Local action of phosphate depletion and insulin-like growth factor 1 on in vitro production of 1,25-dihydroxyvitamin D by cultured mammalian kidney cells.

“…Our findings demonstrate a local action of phosphate depletion and of IGF 1 (6)(7)(8)(9)(10)(11). Phosphate is a particularly interesting regulator of laOHase: in animals and in humans (6,7,9,10,12,13), dietary phosphate restriction or low phosphate serum concentrations lead to an increase of plasma 1,25-(OH)2D concentration, but in vitro no direct effect of phosphate depletion on 1,25-(OH)2D3 production has so far been evidenced (14,15). Moreover, in vivo, the adaptation of 1,25-(OH)2D3 production to phosphate depletion needs integrity of the hypothalamo-hypophysis axis (16)(17)(18)(19).…”

“…The results of our study provide the first evidence of a local action of phosphate concentration on 1,25(OH)2D3 production, not requiring exogenous IGF I: total phosphate depletion in rabbit's kidney cells and partial phosphate depletion in LLC-PK 1 had a clear stimulating effect on 1,25(OH)2D3 production. Trechsel et al (14) in 1979 did not evidence this effect of phosphate depletion while studying cultured chick kidney cells. Two main differences in the experimental protocols may explain these discrepancies: differences in the species origin of the cells, or the use by Trechsel et al (14) of a medium enriched with 10% FCS which may have masked the phosphate effect, while we used a serum and hormone-free medium.…”

“…Trechsel et al (14) in 1979 did not evidence this effect of phosphate depletion while studying cultured chick kidney cells. Two main differences in the experimental protocols may explain these discrepancies: differences in the species origin of the cells, or the use by Trechsel et al (14) of a medium enriched with 10% FCS which may have masked the phosphate effect, while we used a serum and hormone-free medium. Fukase et al (15) in 1982 found an inhibitory effect of high phosphate concentrations on the ability of the mouse kidney cells to produce 1,25 (OH)2D3, but did not detect any effect of phosphate depletion (15).…”

Uterine cells other than stromal decidual cells are required for 1,25‐dihydroxyvitamin D3 production during early human pregnancy

“…Human trophoblastic tissue homogenates produce 1,25-(OH),D, in vitro [9,12,13], but not under all experimental conditions [8], and only when high substrate concentrations are used, 0.1-100 ,uM. Moreover, the K, of this production is higher, 570 nM [12], than that reported for 1,25-(OH),D3 production by kidney cells, 125 nM [15], and trophoblastic tissue may produce 1,25-(OH)2D, in vitro by a mechanism different from the classical one involving the cytochrome P450 mixed function oxidase [13].…”

“…But term decidua parietalis express this capacity when incu- [15], but it is similar to that reported for cultured human pulmonary macrophages from patients with sarcoidosis, 0.4-2.5 pmol/106 cells/h [16]. The results of the present study confirm the ability of cells from human decidual tissue to produce 1,25-(OH),D, in vitro, when incubated with 2.5 or 2500 nM 25-(OH)D, concentrations, and show that this ability is shared by cells isolated during early pregnancy, whether physiological or even ectopic (tubal pregnancy).…”