Duodenal Expression of 25 Hydroxyvitamin D3-1α-hydroxylase Is Higher in Adolescents Than in Children and Adults

Context: Puberty is associated with increased dietary calcium absorption. However, little is known about the metabolic adaptations that enhance calcium absorption during puberty. Objectives: To investigate duodenal 25-hydroxy vitamin D-1 alpha-hydroxylase (CYP 27B1) mRNA expression and duodenal 1,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3) production in children, adolescents, and adults. Design and Methods: CYP27B1and IGF1 mRNA expression and 1,25(OH)(2)D-3 production were determined in duodenal biopsies. CYP27B1 expression was also determined after IGF1R inhibitor treatment of human and mice duodenal explants. mRNA expression was determined by RT-PCR, and CYP27B1 activity was determined by incubating duodenal explants with 25(OH)D-3 and measuring 1,25(OH)(2)D-3 production by radioimmunoassay. Results: CYP27B1 mRNA expression was 13.7 and 10.4 times higher in biopsies from adolescents compared to adults and children, respectively. IGF1 mRNA expression was 30% and 45% higher in explants from adolescents and children, respectively, compared to adults. Inhibition of IGF1 receptor activity decreased CYP27B1 expression in explants from both mice (85%) and humans (24%). 1,25(OH)(2)D-3 production reached a maximum velocity of 768 +/- 268 pmol/l/mg protein at 748.8 nmol/l of 25(OH)D-3 in children and adolescents, whereas the maximum velocity was 86.4 +/- 43.2 pmol/l/mg protein in adults. The substrate concentration at which the enzyme shows half of its maximum activity was similar in all groups, ranging between 624 and 837 nmol/L of 25(OH)D-3. Conclusions: Increased CYP27B1 expression and local duodenal 1,25(OH)(2)D-3 production during puberty may be a metabolic adaptation that promotes dietary calcium absorption. IGF1, a major factor in skeletal growth, is also involved in the modulation of CYP27B1 expression in the gut and may increase calcium supply for the growing bone.