title: Production of 1,25 dihydroxyvitamin D3 by perfused pig skin.
abstract: Keratinocytes produce large amounts of 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) in vitro. 1,25(OH)2D3 is detectable in anephric humans and pigs and can be increased to near-normal levels by vitamin D or 250HD, indicating an extrarenal source. To determine whether the skin is one of these extrarenal sources, we perfused isolated flaps of porcine skin for 8 h with 250HD3 in serum-free medium at 1 ml/min, collecting the venous effluent as 15-min samples. The samples were extracted and the vitamin D metabolites purified by high-performance liquid chromatography and assayed by competitive protein-binding techniques. Production of 1,25(OH)2D3 continued for the duration of the perfusion, tending to increase in the last 2 hours. The amount of 1,25(OH)2D3 produced varied both with time in the same pig skin and between pig skins; maximum production of 1,25(OH)2D3 in these experiments was 8 pg/min. 24,25(OH)2D3 production was higher than 1,25(OH)2D3 production, reaching a maximum rate of 180 pg/min. Considering that the production rate of 1,25(OH)2D3 in humans is 1.25 ng/min and that a 48-cm2 skin flap represents 1/350 the surface area of a human, and assuming that human and pig skin make 1,25(OH)2D3 at comparable rates, one can determine that the skin has the potential to maintain near-normal levels of 1,25(OH)2D3 in the absence of kidneys when provided with adequate substrate.
authors.affiliation: Endocrine Research Unit, Veterans Administration Medical Center, San Francisco, California 94121.
authors.forename: D D
authors.initials: DD
authors.lastname: Bikle
authors.forename: B P
authors.initials: BP
authors.lastname: Halloran
authors.forename: J E
authors.initials: JE
authors.lastname: Riviere
mesh_terms: D015650:24,25-Dihydroxyvitamin D 3 / Q000096:biosynthesis; D000818:Animals; D002117:Calcitriol / Q000096:biosynthesis*; D002845:Chromatography; D016895:Culture Media, Serum-Free; D010477:Perfusion; D012867:Skin / Q000378:metabolism*; D013552:Swine; D013997:Time Factors
chemical_list: D016895:Culture Media, Serum-Free; D015650:24,25-Dihydroxyvitamin D 3; D002117:Calcitriol