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Summary background and aims The human fetal jejunum has been shown to harbour the vitamin D3 (D3 ) nuclear receptor (VDR n ) and to be responsive to calcitriol/1,25-dihydroxyvitamin D3 [1,25(OH)2 D3 ] through modulation of proliferation and differentiation processes. The aim of the study was to evaluate the presence as well as the effect of 1,25(OH)2 D3 exposure on the expression levels of the three key D3 -hydroxylase gene transcripts (25-hydroxylase, CYP27A ; 24-hydroxylase, CYP24 ; 1α-hydroxylase, CYP27B1 ) as well as that of the 1,25(OH)2 D3 -responsive endobiotic/xenobiotic metabolizing enzyme CYP3A4 (which is also considered a major detoxifiying enzyme) in the human proximal and distal intestine.methods Specimens from normal fetuses ranging from 15 to 20 weeks of gestation were obtained following elective termination of normal pregnancies. Intestinal explants were cultured for a period of 24 h or 48 h with 10-7 m 1,25(OH)2 D3 . All data were compared to paired-control cultures without 1,25(OH)2 D3 . Total RNA was extracted and cDNA synthesized by RT-PCR. The cDNA obtained was amplified by radioactive PCR, the signal intensity evaluated by densitometric analyses and expressed in relation to the levels of GAPDH . results Data indicate that VDR n , the three D3 -hydroxylases as well as CYP3A4 are expressed in all segments of the human fetal small intestine and in the colon. Basal expression levels of VDR n , CYP27A , CYP24 and CYP3A4 were found to be similar in the proximal, median and distal jejunum as well an in the proximal and distal colon. In contrast, basal 1α-hydroxylase CYP27B1 expression levels were found to be 65% higher in the colon than in the small intestine (P < 0·02). The 1α-hydroxylase was also found to be... [ABSTRACT FROM AUTHOR] |
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