25(OH)D3 metabolism in kidney cell cultures: lack of a direct effect of estradiol

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Abstract
There are several reports of increased production of 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] by the kidney of birds in response to estrogen treatment. To determine whether estradiol influences the renal cell directly, primary cultures of chick kidney cells were exposed to the steroid under a variety of conditions. In the absence of 1,25(OH)2D3, treatment of cultures for 20-24 h with 10(-5) and 10(-6) M estradiol led to inhibition of 25-hydroxyvitamin D3 [25(OH)D3]-1-hydroxylase activity. When the 1-hydroxylase was suppressed and 25(OH)2D3-24-hydroxylase was induced by treatment with 1,25(OH)2D3, estradiol in concentrations of 10(-9) and 10(-5) M either had no effect or slightly inhibited 1,25(OH)2D3 production. Similarly, 24R,25-dihydroxyvitamin D3[24,25(OH)2D3] production was not affected consistently by estradiol. These results were unaltered when either testosterone (10(-6) M) or insulin (5 micrograms/ml) was present in the medium. Shorter treatments (0.5, 2, 4, and 8 h) with estradiol resulted in a transient decrease in both 1,25(OH)2D3 and 24,25(OH)2D3 production, but at no time was stimulation observed. These results suggest that the effects of estrogens on 25(OH)D3 metabolism observed in vivo are exerted elsewhere than directly at the renal cell.