J. Biol. Chem., Vol. 260, Issue 6, 3259-3264, Mar, 1985
Regulation of rat yolk sac 25-hydroxy- and 1,25-dihydroxyvitamin D3 24- hydroxylase activities
JL Danan and H Mathieu
The yolk sac of the pregnant rat which functions as a true placenta is a
target organ for vitamin D. This tissue can hydroxylate in position 24 both
25-hydroxy- and 1,25-dihydroxyvitamin D3 (25-OHD3 and 1,25- (OH)2D3). The
present report describes an in vitro model for the study of 1,25-(OH)2D3
action on the further metabolism of 25-OH[3H]D3 and 1,25-(OH)2[3H]D3 by
yolk sac. The tissue explants were preincubated with 1,25-(OH)2D3 for 18 h
in a serum-free culture medium. Physiological concentrations of
1,25-(OH)2D3 were the most effective in stimulating (7.5-fold) the
1,25-(OH)2D3 24-hydroxylase, while the 25- OHD3 24-hydroxylase stimulation
(4-fold) required a 1,25-(OH)2D3 concentration of 10(-7) M. The stimulating
effect of 1,25-(OH)2D3 on the 1,25-(OH)2D3 24-hydroxylase was
temperature-dependent, and, since its was inhibited by actinomycin D and
cycloheximide, required de novo protein synthesis. 1,24,25-(OH)3D3,
25-OHD3, and 24,25-(OH)2D3 were 10- to 1000-fold less potent than
1,25-(OH)2D3 in inducing the 1,25-(OH)2D3 hydroxylase. Our results strongly
suggest that 1,25-(OH)2D3 regulated the 1,25-(OH)2D3 24-hydroxylase by a
receptor-mediated process. Furthermore, 1,25-(OH)2D3 at 10(-9) M induced
within 4 h an increase of its own degradation and the formation of an as
yet unidentified major 1,25-(OH)2[3H]D3 metabolite. We conclude that the
yolk sac can participate in the regulation of 1,25-(OH)2D3 concentration in
the fetoplacental unit.
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