title: Modulation of CYP27B1 and CYP24 mRNA expression in bone is independent of circulating 1,25(OH)2D3 levels.
abstract: Circulating levels of 1,25-dihydroxyvitamin D (1,25D) are determined by bioactivation catalyzed by the renal 25-hydroxyvitamin D 1alpha-hydroxylase (CYP27B1) and degradation through the action of the renal 25-hydroxyvitamin D 24-hydroxylase (CYP24). CYP27B1 and CYP24 are also present in bone cells, but little is known of their physiological role. The purpose of this study was to determine the changes that occur with aging on the expression of CYP27B1 and CYP24 mRNA in whole kidney and femora of female Sprague-Dawley rats. Real-time RT-PCR was used to measure CYP27B1, CYP24 and vitamin D receptor (VDR) mRNA levels in the kidneys and bones of animals aged between 3 weeks and 2 years. Circulating 1,25D levels decreased exponentially with age which was correlated with both reduced kidney CYP27B1 mRNA (R(2) = 0.72) and increased CYP24 mRNA levels (R(2) = 0.71). In the bone, CYP27B1 mRNA levels were maintained at their highest level throughout the ages of 3 to 15 weeks before decreasing in adult animals (P < 0.05). Bone CYP24 mRNA levels were positively correlated with bone CYP27B1 mRNA and not circulating 1,25D levels (R(2) = 0.74). Levels of bone CYP27B1 mRNA were positively correlated with distal femoral epiphyseal trabecular number (Tb.N) (R(2) = 0.74) and negatively with the trabecular thickness (Tb.Th) (R(2) = 0.56) in animals aged between 12 weeks and 2 years. These findings indicate that the regulation of CYP27B1 and CYP24 mRNA expression in the bone is unique from that in the kidney. The synthesis of 1,25D in bone tissue regulates bone CYP24 expression and is associated with bone mineralization suggesting that vitamin D metabolism has an autocrine or paracrine function.
authors.affiliation: Endocrine Bone Research Laboratory, Hanson Institute, Adelaide, SA, Australia. paul.anderson@imvs.sa.gov.au
authors.forename: Paul H
authors.initials: PH
authors.lastname: Anderson
authors.forename: Peter D
authors.initials: PD
authors.lastname: O'Loughlin
authors.forename: Brian K
authors.initials: BK
authors.lastname: May
authors.forename: Howard A
authors.initials: HA
authors.lastname: Morris
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics*; D000818:Animals; D001842:Bone and Bones / Q000033:anatomy & histology / Q000201:enzymology*; D002117:Calcitriol / Q000097:blood*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D007668:Kidney / Q000201:enzymology; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018167:Receptors, Calcitriol / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013250:Steroid Hydroxylases / Q000235:genetics*; D065668:Vitamin D3 24-Hydroxylase
chemical_list: D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002117:Calcitriol