Abstract
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.
Highlights
From the Unite de Recherches sur le Metabolism Hydro-Miniral, Institut National de la Santd et de la Recherche Mkdicale, INSERM U.120, 78110Le Vesinet, France
The stimulat- 1,25-(OH).& receptor in the adult [19,21,23].it is ing effect of 1,25-(OH)2D3on the 1,25-(OH)& 24- not known whether the regulation of the 24-hydroxylation of hydroxylasewas temperature-dependent, ands,inceits vitamin D metabolites is under the control of 1,25-(OH)2D3 was inhibited by actinomycin D and cycloheximide, in the fetoplacental unit
Therat yolk sac is one of the fetal membranes which possesses true placental functions and surrounds the fetus until the end of gestation [1].We recently showed that the rat yolk sac must be considered as a steroid hormone-sensitive organ deeply involvedin themetabolism and action of vitamin D in the fetus
Summary
From the Unite de Recherches sur le Metabolism Hydro-Miniral, Institut National de la Santd et de la Recherche Mkdicale, INSERM U.120, 78110Le Vesinet, France. Taken immediately after death, or after a 18-h preincubation in the presence of lo-' M 1,25-(OH)2D3or ethanol alone were incubated for 5 h in the culture medium containing [35S]methionineT.
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