title: Androgens Attenuate Vitamin D Production Induced by UVB Irradiation of the Skin of Male Mice by an Enzymatic Mechanism.
abstract: Cutaneous exposure to UVB irradiation is an important source of vitamin D. Here, we examined sex-specific differences in cutaneous vitamin D production in mice. Both male and female mice on a vitamin D-deficient diet manifested vitamin D deficiency, with mineral abnormalities, secondary hyperparathyroidism, and osteomalacia. UVB irradiation significantly increased vitamin D levels in the skin of female mice and normalized serum 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 levels, as well as mineral and skeletal abnormalities. However, in male mice, the vitamin D response to UVB was attenuated and mineral and skeletal abnormalities were not normalized. The vitamin D precursor, 7-dehydrocholesterol (7DHC), was significantly lower in the skin of male than female mice. This reduction was due to local androgen action in the skin as demonstrated by castration studies and skin-specific androgen receptor deletion in male mice, both of which reversed the male phenotype. Local androgen regulation in the skin of the CYP11A1 gene, which encodes a crucial enzyme that metabolizes cholesterol, 7DHC, and vitamin D, appeared to contribute to the gender differences in UVB-induced vitamin D production and to its reversal of vitamin D deficiency. Sex-specific, enzymatically regulated differences in cutaneous production of vitamin D may therefore be of importance to ensure vitamin D sufficiency.
authors.affiliation: Department of Medicine, Calcium Research Laboratory and the Centre for Translational Biology, McGill University Health Centre Montreal, Montreal, Quebec, Canada.
authors.forename: Yingben
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Children's Hospital Oakland Research Institute, Oakland, California, USA.
authors.forename: Lee
authors.initials: L
authors.lastname: Ying
authors.affiliation: Heartland Assays LLC. 2711 South Loop Drive, Suite 4400, Ames, Iowa, USA.
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Horst
authors.affiliation: Children's Hospital Oakland Research Institute, Oakland, California, USA.
authors.forename: Gordon
authors.initials: G
authors.lastname: Watson
authors.affiliation: Department of Medicine, Calcium Research Laboratory and the Centre for Translational Biology, McGill University Health Centre Montreal, Montreal, Quebec, Canada. Electronic address: david.goltzman@mcgill.ca.
authors.forename: David
authors.initials: D
authors.lastname: Goltzman
mesh_terms: D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D015519:Bone Density; D002112:Calcifediol / Q000097:blood; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics; D003684:Dehydrocholesterols / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011944:Receptors, Androgen / Q000502:physiology; D012727:Sex Characteristics; D012867:Skin / Q000378:metabolism / Q000528:radiation effects*; D014466:Ultraviolet Rays; D014807:Vitamin D / Q000096:biosynthesis*
chemical_list: D000728:Androgens; D003684:Dehydrocholesterols; D011944:Receptors, Androgen; D014807:Vitamin D; C016705:7-dehydrocholesterol; D002786:Cholesterol Side-Chain Cleavage Enzyme; D002112:Calcifediol