Kidney deletions of Cyp27b1 fail to reduce serum 1,25(OH)2D3 (in mice)
J Steroid Biochem Mol Biol . 2025 Jun:250:106734. doi: 10.1016/j.jsbmb.2025.106734 PDF snippits available online
Seong Min Lee 1, Shannon R Cichanski 1, Nicolas G Pintozzi 1, Martin Kaufmann 2, Glenville Jones 3, Mark B Meyer 4
Vitamin D metabolism is controlled through the kidney mitochondrial P450 enzymes 1α-hydroxylase (CYP27B1) and 24-hydroxylase (CYP24A1) that activate and degrade the endocrine vitamin D hormone (1,25(OH)2D3), respectively. We recently demonstrated that extrarenal cells can make 1,25(OH)2D3 with adequate vitamin D supplementation by targeted mass spectrometry imaging in our Cyp27b1 kidney enhancer deletion mouse model that lacks circulating 1,25(OH)2D3 (M1/M21-DIKO mouse). Based on these observations, we selectively deleted Cyp27b1 (Cyp27b1fl/fl) from the mouse kidney using the Six2- and Pax8-cre drivers that target tubule and nephron development to see if we could recapitulate the remarkable phenotype of the M1/M21-DIKO mice. While Six2-cre/Cyp27b1fl/fl mice had a mild phenotype, Pax8-cre/Cyp27b1fl/fl mice had a marked elevation of parathyroid hormone and a reduction in bone mineral density. The vitamin D metabolic profile in the Pax8-cre/Cyp27b1fl/fl clearly indicated a dysfunction in the CYP24A1 enzyme with reductions in 24,25(OH)2D3 and 25(OH)D3-26,23-lactone with an accompanying elevation of 25(OH)D3. However, despite these compensatory reductions in CYP24A1 derived metabolites and apparent deletion of Cyp27b1 in the kidney, the 1,25(OH)2D3 levels were not changed from wildtype in either mouse. Like 24,25(OH)2D3, the 1,24,25(OH)3D3 levels were also reduced. These data highlight the robust homeostatic mechanisms to salvage 1,25(OH)2D3, point towards potential compensatory mechanisms of 1,25(OH)2D3 production from non-kidney tissues, and reinforce the utility of the M1/M21-DIKO model as a non-global deletion of Cyp27b1 with reductions in serum 1,25(OH)2D3 to be used to understand the complexity of vitamin D metabolism in health and inflammatory disease.
VitaminDWiki – CYP27B1 category contains
The CYP27B1 gene activates Vitamin D in the Kidney, Skin, Lungs, Brain, Eyes Breasts etc.
Poor CYP27B1 is assocated with COVID, Miscarriage, Lupus, Alz, Parkinson, MSA, Rickets
CYtochrome P450 family 27 subfamily B member 1 = 25-Hydroxyvitamin D3 1-alpha-hydroxylase
64 items in CYP27B1 category 346 articles in the Genetics 537 articles in Vitamin D Receptor 178 articles in Vitamin D Binding Protein - CYP27B1 and other genes are less activated in seniors
- CYP27B causes many health problems – March 2020
- Every Parkinson’s brain had a poor CYP27B1 gene
What can be done if have a poor CYP27B1
- Larger doses of Vitamin D
- More Bio-available: Gut-friendly form, Topical form, taken with fatty meal, taken with evening meal
- Additional sources: UV
- Increase Vitamin D metabolism: additional Magnesium, Omega-3
- All cytochrome P450 enzymes require Mg++ as a cofactor
- Increase the amount of Vitamin D in the blood that gets to cells: increase activation of VDR
Vitamin D blood test misses CYP27B1 and other genes
Note from above chart: CYP27B1 is required, but not necessarily in the Kidney
Kidney may not be required to activate Vitamin D - April 2025Printer Friendly Follow this page for updates41 visitors, last modified 11 Apr, 2025, This page is in the following categories (# of items in each category)