Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P02774 (Gc-globulin)
 196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We evaluated the effect of estrogens on "free" and total calcitriol levels and on the calcitriol response to a hypocalcemic challenge in 12 postmenopausal women, age 55-74 yr. Endogenous calcitriol production was induced by intravenous Na-EDTA before and after conjugated estrogens, 1.25 mg/d for 30 d. Free calcitriol was determined by centrifugal ultrafiltration and by the molar ratio of calcitriol to vitamin D-binding protein (DBP). Estrogen increased fasting total calcitriol from 38.5 +/- 3.8 to 62.3 +/- 7.0 pg/ml (P less than 0.05). This was accompanied by a rise in free calcitriol from 104.5 +/- 11.4 to 158.7 +/- 16.4 fg/ml (P less than 0.05). Vitamin D-binding protein increased from 348 +/- 16 to 428 +/- 12 micrograms/ml (P less than 0.001), and the ratio of calcitriol/DBP increased from 1.50 +/- 0.14 to 1.94 +/- 0.18 (P less than 0.005), confirming the rise in free calcitriol. Increases in free calcitriol and in calcitriol/DBP ratios were significantly correlated, r = 0.72. Hypocalcemia led to a rapid increase in circulating immunoreactive parathyroid hormone, and to a rise in calcitriol at 24 h. The hypocalcemia-induced rise in total and free calcitriol was similar before and after estrogen, whether expressed as increments or as percent changes. We conclude that estrogen increases circulating levels of biologically active free calcitriol in postmenopausal women, but that a 30-d period of estrogen administration does not apparently improve the renal 1 alpha-hydroxylase response to a PTH challenge.
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PMID:Effects of estrogen on circulating "free" and total 1,25-dihydroxyvitamin D and on the parathyroid-vitamin D axis in postmenopausal women. 249 9

Vitamin D-binding protein (DBP) is a multi-functional serum protein that is converted to vitamin D-binding protein-macrophage activating factor (DBP-maf) by post-translational modification. DBP-maf is a new cytokine that mediates bone resorption by activating osteoclasts, which are responsible for resorption of bone. Defective osteoclast activation leads to disorders like osteopetrosis, characterized by excessive accumulation of bone mass. Previous studies demonstrated that two nonallelic mutations in the rat with osteopetrosis have independent defects in the cascade involved in the conversion of DBP to DBP-maf. The skeletal defects associated with osteopetrosis are corrected in these mutants with in vivo DBP-maf treatment. This study evaluates the effects of various forms of DBP-maf (native, recombinant, and 25-hydroxyvitamin D(3) bound) on osteoclast function in vitro in order to determine some of the structural requirements of this protein that relate to bone resorbing activities. Osteoclast activity was determined by evaluating pit formation using osteoclasts, isolated from the long bones of newborn rats, incubated on calcium phosphate coated, thin film, Ostologic MultiTest Slides. Incubation of osteoclasts with ex vivo generated native DBP-maf resulted in a dose dependent, statistically significant, activation of the osteoclasts. The activation was similar whether or not the vitamin D binding site of the DBP-maf was occupied. The level of activity in response to DBP-maf was greater than that elicited by optimal doses of other known stimulators (PTH and 1,25(OH(2)D(3)) of osteoclast function. Furthermore, another potent macrophage activating factor, interferon--gamma, had no effect on osteoclast activity. The activated form of a full length recombinant DBP, expressed in E. coli showed no activity in the in vitro assay. Contrary to this finding, baculovirus-expressed recombinant DBP-maf demonstrated significant osteoclast activating activity. The normal conversion of DBP to DBP-maf requires the selective removal of galactose and sialic acid from the third domain of the protein. Hence, the differential effects of the two recombinant forms of DBP-maf is most likely related to glycosylation; E. coli expressed recombinant DBP is non-glycosylated, whereas the baculovirus expressed form is glycosylated. These data support the essential role of glycosylation for the osteoclast activating property of DBP-maf.
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PMID:Baculovirus-expressed vitamin D-binding protein-macrophage activating factor (DBP-maf) activates osteoclasts and binding of 25-hydroxyvitamin D(3) does not influence this activity. 1125 36