25-Hydroxylation of vitamin D3: relation to circulating vitamin D3 under various input conditions.

Background: Neither the efficiency of the 25-hydroxylation of vitamin D nor the steady state relation between vitamin D(3) and 25-hydroxyvitamin D [25(OH)D] has been studied in humans.

Objective: We aimed to examine the relation between serum vitamin D(3) and 25(OH)D in normal subjects after either oral administration of vitamin D(3) or ultraviolet-B radiation across a broad range of inputs.

Design: Values for serum vitamin D(3) and (OH)D(3) were aggregated from 6 studies--1 acute and 5 near-steady state--at various vitamin D(3) inputs.

Mutational analysis of CYP27A1: assessment of 27-hydroxylation of cholesterol and 25-hydroxylation of vitamin D.

The CYP27A1 gene encodes a mitochondrial enzyme that modulates the acidic biosynthetic pathway for bile acids beginning with the 27-hydroxylation of cholesterol. CYP27A1 also 25-hydroxylates vitamin D(3). Gene mutations cause cerebrotendinous xanthomatosis (CTX), an autosomal recessive disorder, and may cause 25-hydroxyvitamin D deficiency and early-onset osteoporosis and fractures in affected patients.

Characterization of recombinant CYP2C11: a vitamin D 25-hydroxylase and 24-hydroxylase.

Studies were performed to further characterize the male-specific hepatic recombinant microsomal vitamin D 25-hydroxlase CYP2C11, expressed in baculovirus-infected insect cells, and determine whether it is also a vitamin D 24-hydroxylase. 25- and 24-hydroxylase activities were compared with those of 10 other recombinant hepatic microsomal cytochrome P-450 enzymes expressed in baculovirus-infected insect cells. Each of them 25-hydroxylated vitamin D2, vitamin D3, 1alpha-hydroxyvitamin D2 (1alphaOHD2), and 1alpha-hydroxyvitamin D3 (1alphaOHD3).

CYP3A4 is a vitamin D-24- and 25-hydroxylase: analysis of structure function by site-directed mutagenesis.

Studies were performed to identify the microsomal enzyme that 24-hydroxylates vitamin D, whether 25-hydroxylation occurs, and structure function of the enzyme. Sixteen hepatic recombinant microsomal cytochrome P450 enzymes expressed in baculovirus-infected insect cells were screened for 24-hydroxylase activity. CYP3A4, a vitamin D-25-hydroxylase, and CYP1A1 had the highest 24-hydroxylase activity with 1 alpha-hydroxyvitamin D(2) (1 alpha OHD(2)) as substrate.

Genetic evidence that the human CYP2R1 enzyme is a key vitamin D 25-hydroxylase.

The synthesis of bioactive vitamin D requires hydroxylation at the 1 alpha and 25 positions by cytochrome P450 enzymes in the kidney and liver, respectively. The mitochondrial enzyme CYP27B1 catalyzes 1 alpha-hydroxylation in the kidney but the identity of the hepatic 25-hydroxylase has remained unclear for >30 years. We previously identified the microsomal CYP2R1 protein as a potential candidate for the liver vitamin D 25-hydroxylase based on the enzyme's biochemical properties, conservation, and expression pattern.

CYP3A4 is a human microsomal vitamin D 25-hydroxylase.

Unlabelled: The human hepatic microsomal vitamin D 25-hydroxylase protein and gene have not been identified with certainty. Sixteen hepatic recombinant microsomal enzymes were screened for 25-hydroxylase activity; 11 had some 25-hydroxylase activity, but CYP3A4 had the highest activity. In characterized liver microsomes, 25-hydroxylase activity correlated significantly with CYP3A4 testosterone 6beta-hydroxylase activity.

Primary squamous cell carcinoma of the thyroid gland.

A case of primary squamous cell carcinoma of the thyroid is presented. Squamous epithelium is normally not present in the thyroid gland, and this tumor is exceedingly rare. Proper workup is described, including the differentiation from metastatic disease.

Significant differential effects of alendronate, estrogen, or combination therapy on the rate of bone loss after discontinuation of treatment of postmenopausal osteoporosis. A randomized, double-blind, placebo-controlled trial.

Background: Combination therapy with alendronate and estrogen for 2 years increases bone mineral density at the spine and hip more than does therapy with either agent alone. Changes in bone mineral density after discontinuation of therapy have not been compared directly.

Objective: To determine the rate of bone loss when therapy with alendronate, estrogen, or both agents is discontinued.

Alendronate increases bone mass and reduces bone markers in postmenopausal African-American women.

Previous studies indicated that aminobisphosphonate alendronate sodium, a potent inhibitor of bone resorption, increases bone mineral density (BMD) at the hip and spine, reduces markers of bone turnover, and reduces the risk of fractures in Caucasian postmenopausal women. The purpose of the present study was to investigate whether alendronate increases BMD and reduces markers of bone turnover in African-American postmenopausal women. In a multicenter, randomized, double-blind, placebo-controlled study, 65 African-American women, aged 45 to 88 yr, were randomly assigned to either placebo (n = 33) or alendronate 10 mg daily (n = 32) for 2 yr.