The Journal of steroid biochemistry and molecular biology
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J. Steroid Biochem. Mol. Biol. · Nov 2017
Vitamin D deficiency is associated with poor breast cancer prognostic features in postmenopausal women.
This study aimed to evaluate the association between pretreatment vitamin D (VD) deficiency with breast cancer prognostic features in Brazilian postmenopausal women. An analytical cross sectional study was conducted with 192 women, aged 45-75 years, attended at University Hospital. Women with recent diagnosis of breast cancer, in amenorrhea >12months and age ≥45 years, without medication use or clinical conditions that interfere with VD values were included. ⋯ Multivariate analysis, after adjusting for age, time since menopause and BMI, showed that insufficient and deficient level of vitamin D were significantly associated with negative estrogen receptor (OR 3.77 CI 95% 1.76-8.09 and OR 3.99 CI 95% 1.83-8.68), high Ki-67 (OR 2.50, CI 95% 1.35-4.63, and OR 2.62, CI 95% 1.40-4.98), and positive axillary lymph node status (OR 1.59, CI 95% 1.03-2.33, and OR 1.58, CI 95% 1.02-2.92) respectively. In Brazilian postmenopausal women with breast cancer, there was an association between vitamin D insufficiency or deficiency and tumors with worse prognostic features. Low vitamin D levels were shown to be a risk factor for ER negative tumors, with positive axilla and a higher rate of cell proliferation.
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J. Steroid Biochem. Mol. Biol. · Mar 2017
Vitamin D metabolite concentrations in umbilical cord blood serum and associations with clinical characteristics in a large prospective mother-infant cohort in Ireland.
Vitamin D deficiency is widespread among mothers and neonates and quality clinical and analytical data are lacking. We used a CDC-accredited LC-MS/MS method to analyze vitamin D metabolites in cord sera from 1050 maternal-infant dyads in the prospective SCOPE Ireland Pregnancy and BASELINE Birth cohort studies, based in Cork, Ireland. The mean±SD total 25(OH)D was 34.9±18.1nmol/L; 35% of cords (50% during winter) had 25(OH)D <25nmol/L, 46% were <30nmol/L and 80% were <50nmol/L. ⋯ Cord 3-epi-25(OH)D3 concentrations were positively predicted by cord 25(OH)D3 [0.101 (0.099, 0.103) nmol/L, P<0.0001] and negatively by gestational age [-0.104 (-0.131, -0.076) nmol/L, P<0.0001] and maternal age [-0.010 (-0.019, -0.001) nmol/L, P<0.05]. 25(OH)D2 was detected in 98% of cord sera (mean±SD; 2.2±1.9nmol/L) despite low antenatal consumption of vitamin D2 supplements. In conclusion, these first CDC-accredited data of vitamin D metabolites in umbilical cord blood emphasise the high risk of very low vitamin D status in infants born to un-supplemented mothers. Experimental data to define maternal vitamin D requirements for prevention of neonatal deficiency at high latitude are required.
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J. Steroid Biochem. Mol. Biol. · Mar 2017
Comparative StudyComparison of the effects of novel vitamin D receptor analog VS-105 and paricalcitol on chronic kidney disease-mineral bone disorder in an experimental model of chronic kidney disease.
When using vitamin D, the most important clinical problems are hypercalcemia, hyperphosphatemia, and vascular calcification. VS-105 is a novel vitamin D receptor (VDR) analog. In the present study, we compared the effects of VS-105 and paricalcitol on chronic kidney disease-mineral bone disorder (CKD-MBD) in a CKD rat model. ⋯ VDR and Klotho expression in the kidney was significantly higher in the VS-105-treated groups than in the paricalcitol-treated groups although both agents increased these expressions. Our data suggest that VS-105 had a lesser effect on CKD-MBD than paricalcitol except in the case of serum PTH levels. The mechanism appears to be associated with the difference in VDR and Klotho expression.
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J. Steroid Biochem. Mol. Biol. · Mar 2017
Vitamin D receptor agonist VS-105 directly modulates parathyroid hormone expression in human parathyroid cells and in 5/6 nephrectomized rats.
Vitamin D receptor (VDR) agonists (VDRAs) are commonly used to treat secondary hyperparathyroidism (SHPT) associated with chronic kidney disease (CKD). Current VDRA therapy often causes hypercalcemia, which is a critical risk for vascular calcification. Previously we have shown that a novel VDRA, VS-105, effectively suppresses serum parathyroid hormone (PTH) without affecting serum calcium levels in 5/6 nephrectomized (NX) uremic rats. ⋯ In 5/6 NX rats, one single dose of 0.05-0.2μg/kg of VS-105 or 0.02-0.04μg/kg of paricalcitol effectively reduced serum PTH by >40% on Day 2. Serum PTH remained suppressed during the dosing period, but tended to rebound in the paricalcitol groups. These data indicate that VS-105 exerts a rapid effect on suppressing serum PTH, directly down-regulates the PTH gene, and modulates PTH, VDR and CaSR gene expression more effectively than paricalcitol.
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J. Steroid Biochem. Mol. Biol. · Jan 2017
Multiplexed steroid profiling of gluco- and mineralocorticoids pathways using a liquid chromatography tandem mass spectrometry method.
Serum steroid assays are major tools in the clinical evaluation of adrenal disorders. The main adrenal steroids are routinely measured with immunoassays. However, chromatographic methods are known to offer better specificity. ⋯ However, Bland-Altman plots revealed large negative bias for aldosterone (-33.4%, AldoCT, CisBio international), for 17-hydroxyprogesterone at concentrations below 2ng/mL (-74.1%, OHP-CT MP Biomedical), for androstenedione (-80.3%, RIA D4, Beckman Coulter) and for 11-deoxycortisol (-125.3%, Diasource Immunoassays). Finally, the analysis of samples from 21-hydroxylase defective patients demonstrated the potential usefulness of multiplexed steroid profiling for the diagnosis and/or monitoring of different forms of congenital adrenal hyperplasia. This LC-MS/MS method provides highly sensitive and specific assessments of mineralo- and glucocorticoids pathways from a small volume sample and is therefore a promising potent tool for clinical and experimental endocrine studies.