AJP - Gastrointestinal and Liver Physiology, Vol 258, Issue 4 557-G563, Copyright © 1990 by American Physiological Society
1,25-Dihydroxyvitamin D3-inducible catabolism of vitamin D metabolites in mouse intestine
M. Tomon, H. S. Tenenhouse and G. Jones
Department of Pediatrics, McGill University-Montreal Children's Hospital Research Institute, Quebec, Canada.
The 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]-inducible C-24 oxidation pathway
is a major catabolic pathway for vitamin D metabolites in target tissues.
Using intestinal homogenates derived from 1,25(OH)2D3-treated mice, we
examined the time course of induction, the intestinal localization and
kinetics of induced enzyme activity, as well as the sensitivity of
induction to transcriptional inhibitors actinomycin D and alpha-amanitin.
24-Hydroxylation of 500 nM 3H-labeled 25-hydroxyvitamin D3 [25(OH)D3] and
50 nM 3H-labeled 1,25(OH)2D3 by duodenal homogenates was detected 1 h after
1,25(OH)2D3 treatment; C-24 oxidation products of 25(OH)D3 and 1,25(OH)2D3
peaked at approximately 6 h and remained elevated for 17 h. Induced enzyme
activity was localized to the mitochondrial fraction, was highest in
duodenum, and was also detected in jejunum, ileum, and colon. The apparent
Michaelis constant of the induced duodenal enzyme for 25(OH)D3 was 451 nM
and for 1,25(OH)2D3 was 14 nM. Induction of intestinal catabolic activity
was inhibited by prior treatment of 1,25(OH)2D3-injected mice with either
actinomycin D or alpha-amanitin. The characteristics of the
1,25(OH)2D3-inducible C-24 oxidation pathway in the intestine resembled
that of the kidney. However, the catabolic pathway was constitutively
expressed only in the kidney. We conclude that 1,25(OH)2D3-inducible
degradation of vitamin D metabolites occurs throughout the length of mouse
intestine and can be prevented by transcriptional inhibitors, suggesting
that mRNA synthesis is required for the induction process.
