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An adequate vitamin D status is essential to optimize muscle strength. However, whether vitamin D directly reduces muscle fiber atrophy or stimulates muscle fiber hypertrophy remains subject of debate. A mechanism that may affect the role of vitamin D in the regulation of muscle fiber size is the local conversion of 25(OH)D to 1,25(OH)2D by 1α-hydroxylase. Therefore, we investigated in a murine C2C12 myoblast culture whether both 1,25(OH)2D3 and 25(OH)D3 affect myoblast proliferation, differentiation, and myotube size and whether these cells are able to metabolize 25(OH)D3 and 1,25(OH)2D3. We show that myoblasts not only responded to 1,25(OH)2D3, but also to the precursor 25(OH)D3 by increasing their VDR mRNA expression and reducing their proliferation. In differentiating myoblasts and myotubes 1,25(OH)2D3 as well as 25(OH)D3 stimulated VDR mRNA expression and in myotubes 1,25(OH)2D3 also stimulated MHC mRNA expression. However, this occurred without notable effects on myotube size. Moreover, no effects on the Akt/mTOR signaling pathway as well as MyoD and myogenin mRNA levels were observed. Interestingly, both myoblasts and myotubes expressed CYP27B1 and CYP24 mRNA which are required for vitamin D3 metabolism. Although 1α-hydroxylase activity could not be shown in myotubes, after treatment with 1,25(OH)2D3 or 25(OH)D3 myotubes showed strongly elevated CYP24 mRNA levels compared to untreated cells. Moreover, myotubes were able to convert 25(OH)D3 to 24R,25(OH)2D3 which may play a role in myoblast proliferation and differentiation. These data suggest that skeletal muscle is not only a direct target for vitamin D3 metabolites, but is also able to metabolize 25(OH)D3 and 1,25(OH)2D3. J. Cell. Physiol. 231: 2517-2528, 2016. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background/Aims: The postnatal activation of the hypothalamic-pituitary-gonadal axis is more exaggerated in preterm than in full-term-born infants, and may be important for reproductive function. Our objective was to investigate this activation of the hypothalamic-pituitary-gonadal axis in male very-low-birthweight (VLBW) infants. Methods: Twenty-one VLBW boys (gestational age 26.0-30.0 weeks), participating in the NIRTURE trial, were included. Gonadotropin and testosterone levels were measured in serial urine samples collected at 1 and 4 weeks' postnatal age, at 32 weeks' postmenstrual age, at expected date of delivery and at the corrected age of 3 and 6 months. Results: Longitudinal analysis shows that after birth LH and FSH levels peak at a mean postnatal age of 1-4 weeks (mean postmenstrual age of 30-32 weeks) and decrease until 38 weeks' postnatal age (corrected age of 6 months). Testosterone levels decrease with increasing age, and this decrease is faster in infants receiving early insulin therapy. Conclusions: Serial urine sampling for measurement of gonadotropin and testosterone levels provides accurate information about the postnatal activation of the hypothalamic-pituitary-gonadal axis in VLBW boys. FSH and LH levels peak at 1-4 weeks of age. Insulin treatment causes faster decrease in testosterone levels. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: The hypothalamic circuitry, apart from its impact on food intake, modulates insulin sensitivity to adapt metabolic conditions in the face of environmental fluctuations in nutrient availability. The purpose of the present study was to investigate the effects of 2 weeks high fat feeding in wildtype mice on (1) insulin sensitivity and triglyceride accumulation in liver and muscle in relation to (2) mRNA expression levels of Neuropeptide Y (NPY), Agouti-related protein (AgRP), pro-opiomelanocortin (POMC), and cocaine- and amphetamine-regulated transcript (CART) in the hypothalamus. Two weeks of high fat feeding induced hepatic insulin resistance in the presence of increased hepatic triglyceride accumulation. In muscle, however, 2 weeks of high fat feeding did not result in changes in insulin sensitivity or in triglyceride content. mRNA expression levels of NPY, AgRP, POMC, and CART in the hypothalamus were not different between the groups. This study shows that 2 weeks of high fat feeding in mice does not affect mRNA expression levels of NPY, AgRP, POMC or CART, in the whole hypothalamus, despite induction of hepatic, but not peripheral, insulin resistance. Therefore, a major physiological role of these neuroendocrine factors in the induction of hepatic insulin resistance during a high fat diet seems less likely. [Copyright &y& Elsevier]

• High dose hook effect still occurs in diagnostic laboratories. • Sudden low thyroglobulin level in differentiated thyroid cancer; an analytical flaw. • Interpretation of discordant lab results requires short lines of communication. We describe a case of a patient with metastasized differentiated thyroid carcinoma who was treated with total thyroidectomy followed-up by radioactive iodine treatment. During treatment and follow-up the thyroglobulin levels were assayed which surprisingly did not match the clinical condition. An analytical flaw was suspected. Re-analysis in the laboratory showed the presence of a high dose hook effect (HDH), resulting in falsely low Tg levels. This case shows that HDH effects in immunoassays, like the thyroglobulin assay, still exist in daily practice. Discordance between laboratory results and clinical condition underlines the importance of short lines of communication between clinical chemists and medical doctors. [ABSTRACT FROM AUTHOR]

The metabolite 1,25-dihydroxyvitamin D (1,25(OH) 2 D) is synthesized from its precursor 25-hydroxyvitamin D (25(OH)D) by human osteoblasts leading to stimulation of osteoblast differentiation in an autocrine or paracrine way. Osteoblast differentiation is also stimulated by mechanical loading through activation of various responses in bone cells such as nitric oxide signaling. Whether mechanical loading affects osteoblast differentiation through an enhanced synthesis of 1,25(OH) 2 D by human osteoblasts is still unknown. We hypothesized that mechanical loading stimulates the synthesis of 1,25(OH) 2 D from 25(OH)D in primary human osteoblasts. Since the responsiveness of bone to mechanical stimuli can be altered by various endocrine factors, we also investigated whether 1,25(OH) 2 D or 25(OH)D affect the response of primary human osteoblasts to mechanical loading. Primary human osteoblasts were pre-incubated in medium with/without 25(OH)D 3 (400 nM) or 1,25(OH) 2 D 3 (100 nM) for 24 h and subjected to mechanical loading by pulsatile fluid flow (PFF). The response of osteoblasts to PFF was quantified by measuring nitric oxide, and by PCR analysis. The effect of PFF on the synthesis of 1,25(OH) 2 D 3 was determined by subjecting osteoblasts to PFF followed by 24 h post-incubation in medium with/without 25(OH)D 3 (400 nM). We showed that 1,25(OH) 2 D 3 reduced the PFF-induced NO response in primary human osteoblasts. 25(OH)D 3 did not significantly alter the NO response of primary human osteoblasts to PFF, but 25(OH)D 3 increased osteocalcin and RANKL mRNA levels, similar to 1,25(OH) 2 D 3 . PFF did not increase 1,25(OH) 2 D 3 amounts in our model, even though PFF did increase CYP27B1 mRNA levels and reduced VDR mRNA levels. CYP24 mRNA levels were not affected by PFF, but were strongly increased by both 25(OH)D 3 and 1,25(OH) 2 D 3 . In conclusion, 1,25(OH) 2 D 3 may affect the response of primary human osteoblasts to mechanical stimuli, at least with respect to NO production. Mechanical stimuli may affect local vitamin D metabolism in primary human osteoblasts. Our results suggest that 1,25(OH) 2 D 3 and mechanical loading, both stimuli of the differentiation of osteoblasts, interact at the cellular level. [ABSTRACT FROM AUTHOR]

Objective The objective of our study was to determine reference intervals and biologic variation for testosterone (T), free testosterone (fT), and free androgen index (FAI) in women with accurate methods and to test the discriminative value of these parameters in a polycystic ovary syndrome (PCOS)-population. Methods Serum was obtained daily during a normal menstrual cycle from 25 healthy women (677 data-points). A single serum sample was obtained from 44 PCOS-patients. T was measured by LC–MS/MS and by Architect® 2nd generation T Immunoassay. Sex hormone-binding globulin was measured to calculate fT and FAI. Results Reference intervals which were established in healthy women with an ovulatory menstrual cycle were T = 0.3–1.6 nmol/L and 0.5–2.0 nmol/L, fT = 5.2–26 pmol/L and 7.2–33 pmol/L, and FAI = 0.4–2.9 and 0.6–4.4, by LC–MS/MS and immunoassay, respectively. T, fT and FAI were higher in PCOS patients than in controls (p < 0.0001). The areas under the curve of receiver operator characteristic (ROC) plots were not different for T, fT, or FAI when T was measured by LC–MS/MS versus immunoassay based on prediction of PCOS. FAI and fT were the strongest predictors of PCOS. Conclusions When based upon the appropriate reference intervals and ROC analysis, LC–MS/MS and second generation immunoassay have equivalent clinical utility for the diagnosis of PCOS. [ABSTRACT FROM AUTHOR]

Abstract: Reference values of PTH depend on vitamin D status of the reference population. This is often not described in package inserts. The aim of the present study was therefore to calculate assay specific PTH reference levels in EDTA plasma for the Architect (Abbott) in relation to 25-hydroxyvitamin D (25OHD) levels. The relation between PTH levels, 25OHD, BMI, age, gender and kidney function was determined in a cohort of older individuals from the Longitudinal Aging Study Amsterdam (LASA, n=738, age 55–65years) and in a cohort of healthy individuals from the Netherlands Study of Depression and Anxiety (NESDA, n=633, 18–65years). The LASA cohort is a representative sample of the Dutch older population. As expected, PTH reference values were significantly lower in 25OHD sufficient subjects (25OHD>50nmol/L) than in 25OHD deficient and insufficient subjects. The 97.5th percentile of PTH in 25OHD sufficient subjects was 10pmol/L (94.3pg/mL), which was higher than the upper limit stated by the manufacturer (7.2pmol/L or 68.3pg/mL). The relation between vitamin D and PTH was independent of age, gender, BMI and kidney function. In conclusion, we have shown that it is important to establish PTH reference values in a local reference population taking 25OHD status into account. [Copyright &y& Elsevier]

Abstract: Vitamin D deficiency can lead to several health problems collectively called metabolic bone disease (MBD). One commonly kept reptile species prone to develop MBD if managed incorrectly is the bearded dragon (Pogona vitticeps). This study aimed to determine the extent to which adult female bearded dragons fed a diet low in vitamin D can use stored vitamin D and its metabolites to maintain plasma 25(OH)D3 and 1,25(OH)2D3 concentrations after discontinuing UVb exposure. Blood samples of healthy adult female bearded dragons, exposed to UVb radiation for over 6months were collected (day 0) after which UVb exposure was discontinued for 83days and blood was collected. Blood plasma was analysed for concentrations of total Ca, total P, ionized Ca, uric acid, 25(OH)D3 and 1,25(OH)2D3. There was no significant change in plasma 25(OH)D3 and 1,25(OH)2D3 concentrations during the study. While total Ca and P in whole blood was found to significantly decrease over time (P<0.0088 and 0.0016, respectively), values were within the reference range. Plasma ionized Ca tended (P=0.0525) to decrease during the study. Adult female bearded dragons, previously exposed to UVb, are able to maintain blood vitamin D metabolite concentrations when UVb exposure is discontinued for a period of up to 83days. [Copyright &y& Elsevier]

Vitamin D is an important regulator of calcium and phosphorus homeostasis in animals. It can be acquired from the diet or synthesised de novo when skin is exposed to UVb. Vitamin D deficiency can lead to a complex of diseases collectively called metabolic bone disease (MBD). Diurnal lizards without access to UVb are prone to develop vitamin D deficiency, even when dietary vitamin D 3 is provided. A trial was conducted to determine whether juvenile nocturnal lizards require access to UVb to prevent vitamin D deficiency. All leopard geckos (Eublepharis macularius) were supplemented with dietary vitamin D 3. One group was exposed to low level UVb radiation (33–51 μW/cm2) from hatching until 6 months of age and a second group remained unexposed. Animals were fed ad libitum and their growth and weight gain compared with non-exposed controls. At the end of the trial, blood samples were analysed for vitamin D 3 metabolites. The concentration of the vitamin D 3 metabolite, 25(OH)D 3 , was higher in UVb exposed animals (61 ± 20 vs. 38 ± 8 nmol/L), confirming cutaneous synthesis with UVb exposure. Growth and weight gain were similar in both groups, and this, together with the absence of clinical symptoms, suggests that dietary vitamin D 3 alone can meet the vitamin D requirements for growth of this nocturnal gecko, during the first six months of life. It remains to be investigated whether the higher vitamin D metabolite levels holds other health benefits for this species, such as improved bone density or immune response. Unlabelled Image • The nocturnal leopard gecko synthesizes vitamin D 3 when exposed to UVb. • Low UVb (UVI ≤ 1.6) for 2 h daily increases 25(OH)D 3 levels by 50%. • Dietary vitamin D 3 maintains normal growth and weight gain in juvenile leopard geckos. [ABSTRACT FROM AUTHOR]