| 1. |
- Almokhtar, Mokhtar, et al.
(författare)
-
Motor neuron-like NSC-34 cells as a new model for the study of vitamin D metabolism in the brain.
- 2016
-
Ingår i: Journal of Steroid Biochemistry and Molecular Biology. - : Elsevier BV. - 0960-0760 .- 1879-1220. ; 158, s. 178-188
-
Tidskriftsartikel (refereegranskat)abstract
- Vitamin D-3 is a pro-hormone, which is sequentially activated by 25- and 1 alpha-hydroxylation to form 25-hydroxyvitamin D-3 [25(OH)D-3] and 1 alpha,25-dihydroxyvitamin D-3 [1 alpha,25(OH)2D(3)], respectively. Subsequent inactivation is performed by 24-hydroxylation. These reactions are carried out by a series of CYP450 enzymes. The 25-hydroxylation involves mainly CYP2R1 and CYP27A1, whereas 1 alpha-hydroxylation and 24-hydroxylation are catalyzed by CYP27B1 and CYP24A1, respectively, and are tightly regulated to maintain adequate levels of the active vitamin D hormone, 1 alpha,25(OH)(2)D-3. Altered circulating vitamin D levels, in particular 25(OH)D-3, have been linked to several disorders of the nervous system, e.g., schizophrenia and Parkinson disease. However, little is known about the mechanisms of vitamin D actions in the neurons. In this study, we examined vitamin D metabolism and its regulation in a murine motor neuron-like hybrid cell line, NSC-34. We found that these cells express mRNAs for the four major CYP450 enzymes involved in vitamin D activation and inactivation, and vitamin D receptor (VDR) that mediates vitamin D actions. We also found high levels of CYP24A1-dependent 24,25-dihydroxyvitamin D-3 [24,25(OH)(2)D-3] production, that was inhibited by the well-known CYP enzyme inhibitor ketoconazole and by several inhibitors that are more specific for CYP24A1. Furthermore, CYP24A1 mRNA levels in NSC-34 cells were up-regulated by 1 alpha,25(OH)(2)D-3 and its synthetic analogs, EB1089 and tacalcitol. Our results suggest that NSC-34 cells could be a novel model for the studies of neuronal vitamin D metabolism and its mechanism of actions.
|
|
| 2. |
- Amzaleg, Y., et al.
(författare)
-
Estrogens and selective estrogen receptor modulators differentially antagonize Runx2 in ST2 mesenchymal progenitor cells
- 2018
-
Ingår i: Journal of Steroid Biochemistry and Molecular Biology. - : Elsevier BV. - 0960-0760 .- 1879-1220. ; 183, s. 10-17
-
Tidskriftsartikel (refereegranskat)abstract
- Estrogens attenuate bone turnover by inhibiting both osteoclasts and osteoblasts, in part through antagonizing Runx2. Apparently conflicting, stimulatory effects in osteoblast lineage cells, however, sway the balance between bone resorption and bone formation in favor of the latter. Consistent with this dualism, 17 beta-estradiol (E2) both stimulates and inhibits Runx2 in a locus-specific manner, and here we provide evidence for such locus specific regulation of Runx2 by E2 in vivo. We also demonstrate dual, negative and positive, regulation of Runx2-driven alkaline phosphatase (ALP) activity by increasing E2 concentrations in ST2 osteoblast progenitor cells. We further compared the effects of E2 to those of the Selective Estrogen Receptor Modulators (SERMs) raloxifene (ral) and lasofoxifene (las) and the phytoestrogen puerarin. We found that E2 at the physiological concentrations of 0.1-1 nM, as well as ral and las, but not puerarin, antagonize Runx2-driven ALP activity. At >= 10 nM, E2 and puerarin, but not ral or las, stimulate ALP relative to the activity measured at 0.1-1 nM. Contrasting the difference between E2 and SERMs in ST2 cells, they all shared a similar dose-response profile when inhibiting preosteoclast proliferation. That ral and las poorly mimic the locus-and concentration-dependent effects of E2 in mesenchymal progenitor cells may help explain their limited clinical efficacy.
|
|
| 3. |
- Ankarberg-Lindgren, Carina, 1963, et al.
(författare)
-
High-sensitivity quantification of serum androstenedione, testosterone, dihydrotestosterone, estrone and estradiol by gas chromatography-tandem mass spectrometry with sex- and puberty-specific reference intervals.
- 2018
-
Ingår i: The Journal of steroid biochemistry and molecular biology. - : Elsevier BV. - 1879-1220 .- 0960-0760. ; 183, s. 116-124
-
Tidskriftsartikel (refereegranskat)abstract
- Androgen and estrogen determinations serve as important diagnostic markers in a variety of clinical conditions. However, one challenge is to enhance assay sensitivity for determination in the lowest range, such as in prepubertal children. We here present a recently developed gas chromatography-tandem mass spectrometry (GC-MS/MS) method for determination of androstenedione (A4), dihydrotestosterone (DHT), testosterone (T), estrone (E1), and estradiol (E2) in children, which we have compared with the sensitive radioimmunoassays; E2 extraction-RIA and T-RIA.Steroids were extracted in ethyl acetate n-hexane solution from serum spiked with isotopically labeled internal standard and derivatized sequentially with pentafluorobenzyl bromide, pentafluorobenzyl hydroxylamine and pentafluoropropionic acid anhydride and analyzed by GC-MS/MS using a triple quadrupole mass spectrometer operated in negative chemical ionization mode. Leftover routine samples (n=414) were used to evaluate the concordance between GC-MS/MS and RIAs and the validity of GC-MS/MS for pediatrics; of these samples, 101 were from seemingly healthy children. Pubertal stage was recorded for reference interval evaluation.Lower limit of detection for A4, T, DHT, E1, and E2 were 0.1nmol/L, 0.1nmol/L, 27pmol/L, 9pmol/L, and 2pmol/L, respectively. Good agreement was found between GC-MS/MS and T-RIA (r=0.98) as well as between GC-MS/MS and E2 extraction-RIA (r=0.98, for E2 concentrations above 14pmol/L). In boys, T and DHT increased significantly from prepuberty throughout pubertal development, and in girls the same increase was observed for E1 and E2. The greatest increase in A4 for both genders, as well as E1 and E2 in boys and T and DHT in girls, occurred in mid to late puberty.We report the development of a GC-MS/MS method sensitive enough to accurately determine serum levels of androgens and estrogens in children.
|
|
| 4. |
- Asnake, Solomon, 1985-, et al.
(författare)
-
Species differences in ligand interaction and activation of estrogen receptors in fish and human
- 2019
-
Ingår i: Journal of Steroid Biochemistry and Molecular Biology. - : Pergamon Press. - 0960-0760 .- 1879-1220. ; 195
-
Tidskriftsartikel (refereegranskat)abstract
- Estrogen receptor (ER) sequences vary between species and this suggests that there are differences in the ligand-specificity, leading to species-specific effects. This would indicate that it is not possible to generalize effects across species. In this study, we investigated the differences in activation potencies and binding affinities of ER´s alpha (α) and beta (β) in human, zebrafish and sea bream to elucidate species differences in response to estradiol, estrone, estriol and methyltestosterone. In vitro analysis showed that estradiol had the highest activity for all the ER´s except for human ERβ and seabream ERβ2. Alignment of the ligand binding domain and ligand binding pocket (LBP) residues of the three species showed that different residues were involved in the LBPs which led to differences in pocket volume, affected binding affinity and orientation of the ligands. By combining in silico and in vitro results, it was possible to identify the ligand specificities of ER´s. The results demonstrated that the human ER´s show lower resolution in ligand-dependent activation, suggesting higher promiscuity, than the zebrafish and seabream ER´s. These results show species-specificity of ER´s and suggest that species-specific differences must be taken into consideration when studying different exposure scenarios.
|
|
| 5. |
|
|
| 6. |
- Björk, Anne, et al.
(författare)
-
Variations in the vitamin D receptor gene are not associated with measures of muscle strength, physical performance, or falls in elderly men : Data from MrOS Sweden
- 2019
-
Ingår i: Journal of Steroid Biochemistry and Molecular Biology. - : Elsevier BV. - 0960-0760 .- 1879-1220. ; 187, s. 160-165
-
Tidskriftsartikel (refereegranskat)abstract
- The vitamin D receptor (VDR) has been proposed as a candidate gene for several musculoskeletal phenotypes. However, previous results on the associations between genetic variants of the VDR with muscle strength and falls have been contradictory. The MrOS Sweden survey, a prospective population-based cohort study of 3014 elderly men (mean age 75 years, range 69-81) offered the opportunity to further investigate these associations. At baseline, data were collected on muscle strength and also the prevalence of falls during the previous 12 months. Genetic association analysis was performed for 7 Single Nucleotide Polymorphisms (SNPs), covering the genetic region surrounding the VDR gene in 2924 men with available samples of DNA. Genetic variations in the VDR were not associated with five different measurements of muscle strength or physical performance (hand grip strength right and left, 6 m walking test (easy and narrow) and timed-stands test). However, one of the 7 SNPs of the gene for the VDR receptor, rs7136534, was associated with prevalence of falls (33.6% of the AA, 14.6% of the AG and 16.5% of the GG allele). In conclusion, VDR genetic variants are not related to muscle strength or physical performance in elderly Swedish men. The role of the rs7136534 SNP for the occurrence of falls is not clear.
|
|
| 7. |
- Bärebring, Linnea, et al.
(författare)
-
Serum cortisol and vitamin D status are independently associated with blood pressure in pregnancy
- 2019
-
Ingår i: Journal of Steroid Biochemistry and Molecular Biology. - : Elsevier BV. - 0960-0760. ; 189:May, s. 259-264
-
Tidskriftsartikel (refereegranskat)abstract
- The aim was to study if serum cortisol during pregnancy was associated with blood pressure and development of gestational hypertensive disorders. Additionally, associations between 25-hydroxyvitamin D (25OHD) and cortisol, including confounding effects and interactions in their relation to blood pressure were investigated. In total, 1413 pregnant women from the prospective Swedish GraviD cohort were included. Serum was collected in the first (T1) and third trimester (T3) and analyzed for 25OHD by liquid chromatography mass spectrometry and cortisol using an electro-chemiluminescence immunoassay. The main outcome measures were T1 blood pressure and development of gestational hypertensive disorders (gestational hypertension or preeclampsia). Gestational hypertensive disorders were defined as new onset hypertension, with or without proteinuria, after gestational week 20. Mean ± SD cortisol increased significantly from T1 to T3 (312 ± 123 vs. 659 ± 201 nmol/L, p < 0.001) and this increase was influenced by ethnicity. Serum concentrations of cortisol and 25OHD correlated in both T1 (B = 0.35, p < 0.001) and T3 (B = 0.30, p < 0.001). Cortisol and 25OHD were positively associated with T1 blood pressure, and there were non-significant trends for associations with gestational hypertensive disorders. Cortisol and 25OHD did not display any confounding effect or effect modification in their relationships with blood pressure. In conclusion, there was a positive correlation between serum cortisol and 25OHD in both early and late pregnancy. Both cortisol and 25OHD were positively associated with early pregnancy blood pressure. These results imply that the two hormones might be on different paths in their relationship with blood pressure. © 2019
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Gustafsson, JA, et al.
(författare)
-
Editorial
- 2016
-
Ingår i: The Journal of steroid biochemistry and molecular biology. - : Elsevier BV. - 1879-1220 .- 0960-0760. ; 157, s. 1-2
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
