Duodenal Expression of 25 Hydroxyvitamin D3-1α-hydroxylase Is Higher in Adolescents Than in Children and Adults.
BACKGROUND
Puberty is associated with increased dietary calcium absorption. However, little is known about the metabolic adaptations that enhance calcium absorption during puberty.


OBJECTIVE
To investigate duodenal 25-hydroxy vitamin D-1α-hydroxylase (CYP 27B1) mRNA expression and duodenal 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) production in children, adolescents, and adults.


METHODS
CYP27B1a nd IGF1 mRNA expression and 1,25(OH)2D3 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)D3 and measuring 1,25(OH)2D3 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)2D3 production reached a maximum velocity of 768 ± 268 pmol/l/mg protein at 748.8 nmol/l of 25(OH)D3 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)D3.


CONCLUSIONS
Increased CYP27B1 expression and local duodenal 1,25(OH)2D3 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.
Pediatric Endocrinology (A.G., V.G., D.T.) and Pediatric Gastroenterology (R.S.), Meyer Children's Hospital, Rambam Health Care Campus, Haifa, Israel; Department of Pediatric Endocrinology and Diabetes (A.G.), Medical University of Silesia, Poland; Bone and Mineral Research Division (N.R.), HaEmeck Hospital. Afula, Israel; Gastroenterology Research Laboratory (A.D.) and Endocrinology Research Laboratory (D.B-Y.), Rambam Health Care Campus, Haifa, Israel; Department of Immunology (G.W.), Rappaport Family Institute for Research in the Medical Sciences, The Technion - Israel Institute of Technology, Haifa, Israel; Department of Civil Engineering (O.V.), Faculty of Engineering, Ariel University, Ariel, Israel; Department of Pediatrics (Y.W.), Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; and The Rappaport Faculty of Medicine (D.T., N.R., R.S.,), The Technion- Israel Institute of Technology, Haifa, Israel.
Aneta
A
Gawlik
Pediatric Endocrinology (A.G., V.G., D.T.) and Pediatric Gastroenterology (R.S.), Meyer Children's Hospital, Rambam Health Care Campus, Haifa, Israel; Department of Pediatric Endocrinology and Diabetes (A.G.), Medical University of Silesia, Poland; Bone and Mineral Research Division (N.R.), HaEmeck Hospital. Afula, Israel; Gastroenterology Research Laboratory (A.D.) and Endocrinology Research Laboratory (D.B-Y.), Rambam Health Care Campus, Haifa, Israel; Department of Immunology (G.W.), Rappaport Family Institute for Research in the Medical Sciences, The Technion - Israel Institute of Technology, Haifa, Israel; Department of Civil Engineering (O.V.), Faculty of Engineering, Ariel University, Ariel, Israel; Department of Pediatrics (Y.W.), Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; and The Rappaport Faculty of Medicine (D.T., N.R., R.S.,), The Technion- Israel Institute of Technology, Haifa, Israel.
Vardit
V
Gepstein
Pediatric Endocrinology (A.G., V.G., D.T.) and Pediatric Gastroenterology (R.S.), Meyer Children's Hospital, Rambam Health Care Campus, Haifa, Israel; Department of Pediatric Endocrinology and Diabetes (A.G.), Medical University of Silesia, Poland; Bone and Mineral Research Division (N.R.), HaEmeck Hospital. Afula, Israel; Gastroenterology Research Laboratory (A.D.) and Endocrinology Research Laboratory (D.B-Y.), Rambam Health Care Campus, Haifa, Israel; Department of Immunology (G.W.), Rappaport Family Institute for Research in the Medical Sciences, The Technion - Israel Institute of Technology, Haifa, Israel; Department of Civil Engineering (O.V.), Faculty of Engineering, Ariel University, Ariel, Israel; Department of Pediatrics (Y.W.), Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; and The Rappaport Faculty of Medicine (D.T., N.R., R.S.,), The Technion- Israel Institute of Technology, Haifa, Israel.
Nimrod
N
Rozen
Pediatric Endocrinology (A.G., V.G., D.T.) and Pediatric Gastroenterology (R.S.), Meyer Children's Hospital, Rambam Health Care Campus, Haifa, Israel; Department of Pediatric Endocrinology and Diabetes (A.G.), Medical University of Silesia, Poland; Bone and Mineral Research Division (N.R.), HaEmeck Hospital. Afula, Israel; Gastroenterology Research Laboratory (A.D.) and Endocrinology Research Laboratory (D.B-Y.), Rambam Health Care Campus, Haifa, Israel; Department of Immunology (G.W.), Rappaport Family Institute for Research in the Medical Sciences, The Technion - Israel Institute of Technology, Haifa, Israel; Department of Civil Engineering (O.V.), Faculty of Engineering, Ariel University, Ariel, Israel; Department of Pediatrics (Y.W.), Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; and The Rappaport Faculty of Medicine (D.T., N.R., R.S.,), The Technion- Israel Institute of Technology, Haifa, Israel.
Aviva
A
Dahan
Pediatric Endocrinology (A.G., V.G., D.T.) and Pediatric Gastroenterology (R.S.), Meyer Children's Hospital, Rambam Health Care Campus, Haifa, Israel; Department of Pediatric Endocrinology and Diabetes (A.G.), Medical University of Silesia, Poland; Bone and Mineral Research Division (N.R.), HaEmeck Hospital. Afula, Israel; Gastroenterology Research Laboratory (A.D.) and Endocrinology Research Laboratory (D.B-Y.), Rambam Health Care Campus, Haifa, Israel; Department of Immunology (G.W.), Rappaport Family Institute for Research in the Medical Sciences, The Technion - Israel Institute of Technology, Haifa, Israel; Department of Civil Engineering (O.V.), Faculty of Engineering, Ariel University, Ariel, Israel; Department of Pediatrics (Y.W.), Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; and The Rappaport Faculty of Medicine (D.T., N.R., R.S.,), The Technion- Israel Institute of Technology, Haifa, Israel.
Dafna
D
Ben-Yosef
Pediatric Endocrinology (A.G., V.G., D.T.) and Pediatric Gastroenterology (R.S.), Meyer Children's Hospital, Rambam Health Care Campus, Haifa, Israel; Department of Pediatric Endocrinology and Diabetes (A.G.), Medical University of Silesia, Poland; Bone and Mineral Research Division (N.R.), HaEmeck Hospital. Afula, Israel; Gastroenterology Research Laboratory (A.D.) and Endocrinology Research Laboratory (D.B-Y.), Rambam Health Care Campus, Haifa, Israel; Department of Immunology (G.W.), Rappaport Family Institute for Research in the Medical Sciences, The Technion - Israel Institute of Technology, Haifa, Israel; Department of Civil Engineering (O.V.), Faculty of Engineering, Ariel University, Ariel, Israel; Department of Pediatrics (Y.W.), Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; and The Rappaport Faculty of Medicine (D.T., N.R., R.S.,), The Technion- Israel Institute of Technology, Haifa, Israel.
Gizi
G
Wildbaum
Pediatric Endocrinology (A.G., V.G., D.T.) and Pediatric Gastroenterology (R.S.), Meyer Children's Hospital, Rambam Health Care Campus, Haifa, Israel; Department of Pediatric Endocrinology and Diabetes (A.G.), Medical University of Silesia, Poland; Bone and Mineral Research Division (N.R.), HaEmeck Hospital. Afula, Israel; Gastroenterology Research Laboratory (A.D.) and Endocrinology Research Laboratory (D.B-Y.), Rambam Health Care Campus, Haifa, Israel; Department of Immunology (G.W.), Rappaport Family Institute for Research in the Medical Sciences, The Technion - Israel Institute of Technology, Haifa, Israel; Department of Civil Engineering (O.V.), Faculty of Engineering, Ariel University, Ariel, Israel; Department of Pediatrics (Y.W.), Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; and The Rappaport Faculty of Medicine (D.T., N.R., R.S.,), The Technion- Israel Institute of Technology, Haifa, Israel.
Oleg
O
Verbitsky
Pediatric Endocrinology (A.G., V.G., D.T.) and Pediatric Gastroenterology (R.S.), Meyer Children's Hospital, Rambam Health Care Campus, Haifa, Israel; Department of Pediatric Endocrinology and Diabetes (A.G.), Medical University of Silesia, Poland; Bone and Mineral Research Division (N.R.), HaEmeck Hospital. Afula, Israel; Gastroenterology Research Laboratory (A.D.) and Endocrinology Research Laboratory (D.B-Y.), Rambam Health Care Campus, Haifa, Israel; Department of Immunology (G.W.), Rappaport Family Institute for Research in the Medical Sciences, The Technion - Israel Institute of Technology, Haifa, Israel; Department of Civil Engineering (O.V.), Faculty of Engineering, Ariel University, Ariel, Israel; Department of Pediatrics (Y.W.), Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; and The Rappaport Faculty of Medicine (D.T., N.R., R.S.,), The Technion- Israel Institute of Technology, Haifa, Israel.
Ron
R
Shaoul
Pediatric Endocrinology (A.G., V.G., D.T.) and Pediatric Gastroenterology (R.S.), Meyer Children's Hospital, Rambam Health Care Campus, Haifa, Israel; Department of Pediatric Endocrinology and Diabetes (A.G.), Medical University of Silesia, Poland; Bone and Mineral Research Division (N.R.), HaEmeck Hospital. Afula, Israel; Gastroenterology Research Laboratory (A.D.) and Endocrinology Research Laboratory (D.B-Y.), Rambam Health Care Campus, Haifa, Israel; Department of Immunology (G.W.), Rappaport Family Institute for Research in the Medical Sciences, The Technion - Israel Institute of Technology, Haifa, Israel; Department of Civil Engineering (O.V.), Faculty of Engineering, Ariel University, Ariel, Israel; Department of Pediatrics (Y.W.), Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; and The Rappaport Faculty of Medicine (D.T., N.R., R.S.,), The Technion- Israel Institute of Technology, Haifa, Israel.
Yosef
Y
Weisman
Pediatric Endocrinology (A.G., V.G., D.T.) and Pediatric Gastroenterology (R.S.), Meyer Children's Hospital, Rambam Health Care Campus, Haifa, Israel; Department of Pediatric Endocrinology and Diabetes (A.G.), Medical University of Silesia, Poland; Bone and Mineral Research Division (N.R.), HaEmeck Hospital. Afula, Israel; Gastroenterology Research Laboratory (A.D.) and Endocrinology Research Laboratory (D.B-Y.), Rambam Health Care Campus, Haifa, Israel; Department of Immunology (G.W.), Rappaport Family Institute for Research in the Medical Sciences, The Technion - Israel Institute of Technology, Haifa, Israel; Department of Civil Engineering (O.V.), Faculty of Engineering, Ariel University, Ariel, Israel; Department of Pediatrics (Y.W.), Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; and The Rappaport Faculty of Medicine (D.T., N.R., R.S.,), The Technion- Israel Institute of Technology, Haifa, Israel.
Dov
D
Tiosano
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000818:Animals; D002648:Child; D002675:Child, Preschool; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D011034:Podophyllotoxin / Q000031:analogs & derivatives / Q000494:pharmacology; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors; D012741:Sexual Maturation / Q000187:drug effects / Q000502:physiology*; D055815:Young Adult
C415032:picropodophyllin; D007334:Insulin-Like Growth Factor I; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D017526:Receptor, IGF Type 1; D011034:Podophyllotoxin