Human plasma transport of vitamin D after its endogenous synthesis.

Abstract

IntroductionTransport of vitamin D3 from its sites of cutaneous synthesis into the circulation has been assumed to be via the plasma vitamin D binding protein (DBP). We studied vitamin D transport from the skin in seven healthy volunteers who received whole body irradiation with 27 mJ /cm2 dosage of ultraviolet B light (290-320 nm). Samples of venous blood were collected serially in EDTA and immediately chilled. In KBr, plasma samples were ultracentrifuged to provide a rapid separation of proteins of density < and > 1.3 g/ml. Upper and lower phases and serial fractions were analyzed for vitamin D3 (extraction, HPLC), cholesterol (enzyme assay), and human DBP (hDBP) (radial immunodiffusion). Total plasma vitamin D (basal level < 1 ng/ml) increased by 10 h and peaked at 24 h (9 ± 1 ng/ml). 98% of the D3 remained at the density > 1.3 layers for up to 7 d, whereas cholesterol (> 85%) was detected at density < 1.3 and all of the hDBP was at density > 1. Vitamin D is a precursor ofa renal steroid hormone, 1 ,25-dihydroxyvitamin D (1). This precursor, however, cannot be provided by enzymatic synthesis. Its supply depends on ultraviolet (UV) irradiation ofthe skin or absorption from the diet. Since few natural foodstuffs contain much vitamin D (2), observers consider the endogenous, cutaneous production of cholecalciferol to be the physiological mechanism of precursor supply (2-5).Distinct differences are recognized for the cutaneous synthesis vs. diet-derived supply of vitamin D (2, 6). A more efficient and sustained supply of vitamin D is associated with UV irradiation of the skin or parenteral administration of vitamin D (2, 6). In contrast, oral vitamin D consumption leads to rapid but less sustained availability of sterol and a similar pattern of increase in the hepatic metabolite, 25-hydroxycholecalciferol (2, 6-9).Many studies have addressed the mode of vitamin D transport after oral consumption (6), but no direct studies of the plasma transport of cutaneously-derived vitamin D are reported. It has been assumed that vitamin D synthesized in skin enters the blood stream on the plasma binding protein for vitamin D and its metabolites (DBP)' and this assumption is based on in vitro studies ofthe relative potency of vitamin D in binding to DBP as compared with 7-dehydroxycholesterol, lumisterol, tachysterols3 and pre-D3 (10-12). However, other plasma carriers are recognized and some facilitate hepatic ( 13-15) and hepatocyte (16) Cutaneous irradiation. Seven subjects were exposed to 27 mJ/cm2 of . Venous blood samples were taken at baseline, 10,24, 72, and 168 h after the UV-B exposure, immediately 1. Abbreviation used in this paper: DBP, vitamin D binding protein.

Molecular actions of vitamin D in reproductive cell biology

“…However, these metabolites bind to other carrier proteins including serum albumin and lipoproteins such as chylomicrons that allow transportation in the blood and also facilitate absorption from the gut and subsequent hydroxylation in the liver (Haddad et al 1993). Hydroxylated VitD (25(OH)D) is mainly transported by DBP, and the bioavailability of all metabolites is dependent primarily on the route of VitD entry (cutaneous or dietary) and the mode of plasma transport via association with serum carriers (Haddad et al 1993). The level of these carriers can also vastly alter the free-serum concentration of metabolites, and consequently should be factored into clinical determinations of VitD status.…”

Vitamin D supplementation during pregnancy: safety considerations in the design and interpretation of clinical trials

“…76 Although 25-hydroxylation is not known to be regulated by endocrine feedback inhibition, a constraint on hepatic 25-hydroxylation has been observed, whereby excess circulating D3 is shunted into tissue stores or metabolized when the capacity of the hepatic 25-hydroxylases is exceeded. 77,78 Vitamin D entering the blood via the gastrointestinal route reaches the liver faster than vitamin D endogenously produced in the skin, 79 suggesting a higher risk that 25-hydroxylase function will be overwhelmed and alternative metabolites will be formed following oral vitamin D ingestion in comparison with D3 generated by sun exposure. 80 Recent data suggest that saturation of hepatic 25-hydroxylation activity occurs when the steady-state serum D3 concentration reaches B15 nmol l -1 , above which D3 accumulates in tissues faster than it is 25-hydroxylated.…”

Vitamin D and diabetes

“…In the circulation, all metabolites of vitamin D are bound to a carrier protein known as vitamin D-binding protein [19].…”