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  • 1.
    Akner, Gunnar
    et al.
    Örebro University, School of Health and Medical Sciences.
    Mossberg, K.
    Wikström, A. C.
    Sundqvist, K. G.
    Gustafsson, J. A.
    Evidence for colocalization of glucocorticoid receptor with cytoplasmic microtubules in human gingival fibroblasts, using two different monoclonal anti-GR antibodies, confocal laser scanning microscopy and image analysis1991In: Journal of Steroid Biochemistry and Molecular Biology, ISSN 0960-0760, E-ISSN 1879-1220, Vol. 39, no 4A, p. 419-432Article in journal (Refereed)
    Abstract [en]

    The cellular distribution of the glucocorticoid receptor (GR) in relation to the microtubule protein tubulin was studied in human gingival fibroblasts, using two different anti-GR antibodies of different Ig-classes, by indirect immunofluorescence immunocytology. Further studies were performed by confocal laser scanning microscopy and digital image analysis. The study focused on fluorochrome separation, optical sectioning, digital subtraction techniques and reconstruction of projections obtained using stacks of recorded transversal sections. The data presented further strengthens the notion of a structural colocalization between GR and cytoplasmic microtubules in human fibroblasts.

  • 2.
    Akner, Gunnar
    et al.
    Örebro University, School of Health and Medical Sciences.
    Wikström, A. C.
    Gustafsson, J. A.
    Subcellular distribution of the glucocorticoid receptor and evidence for its association with microtubules1995In: Journal of Steroid Biochemistry and Molecular Biology, ISSN 0960-0760, E-ISSN 1879-1220, Vol. 52, no 1, p. 1-16Article in journal (Refereed)
    Abstract [en]

    The cellular distribution of the glucocorticoid receptor (GR) has not yet been firmly established. The extensive literature indicates that GR is present both in the cytoplasm and the cell nucleus, however, some studies have failed to detect cytoplasmic GR. It is still controversial as to whether GR is randomly diffusing in the cytoplasm and nucleus, or if the GR-distribution is organized or controlled in some way, which may be of importance for the transduction of glucocorticoid effects to cells. There is evidence that both non-activated and activated GR is associated with the plasma membrane, a number of cytoplasmic organelles and the nucleus. Both morphological and biochemical evidence show that GR is associated with microtubules during different stages of the cell cycle, i.e. GR co-localizes, co-purifies and co-polymerizes with tubulin. This indicates that GR is structurally linked to the intracellular MT-network which may be of importance in the mechanism of action of glucocorticoid hormones. The literature in this field is reviewed including the reported data on subcellular GR-localization.

  • 3.
    Asnake, Solomon
    et al.
    Örebro University, School of Science and Technology.
    Modig, Carina
    Örebro University, School of Science and Technology.
    Olsson, Per-Erik
    Örebro University, School of Science and Technology.
    Species differences in ligand interaction and activation of estrogen receptors in fish and human2019In: Journal of Steroid Biochemistry and Molecular Biology, ISSN 0960-0760, E-ISSN 1879-1220, article id 105450Article in journal (Refereed)
    Abstract [en]

    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.

  • 4.
    Humble, Mats B.
    et al.
    Department of Clinical Neuroscience, Division of Psychiatry, St. Göran, Karolinska Institutet, Stockholm, Sweden.
    Gustafsson, Sven
    Department of Laboratory Medicine, Section for Clinical Chemistry, Karolinska Institutet, Stockholm, Sweden.
    Bejerot, Susanne
    Department of Clinical Neuroscience, Division of Psychiatry, St. Göran, Karolinska Institutet, Stockholm, Sweden.
    Low serum levels of 25-hydroxyvitamin D (25-OHD) among psychiatric out-patients in Sweden: relations with season, age, ethnic origin and psychiatric diagnosis2010In: Journal of Steroid Biochemistry and Molecular Biology, ISSN 0960-0760, E-ISSN 1879-1220, Vol. 121, no 1-2, p. 467-470Article in journal (Refereed)
    Abstract [en]

    In a chart review at a psychiatric out-patient department, latitude 59.3 degrees N, a sample of patients with tests of serum 25-hydroxy-vitamin D (25-OHD) and plasma intact parathyroid hormone (iPTH) was collected, together with demographic data and psychiatric diagnoses. During 19 months, 117 patients were included. Their median 25-OHD was 45 nmol/l; considerably lower than published reports on Swedish healthy populations. Only 14.5% had recommended levels (over 75). In 56.4%, 25-OHD was under 50 nmol/l, which is related to several unfavourable health outcomes. Seasonal variation of 25-OHD was blunted. Patients with ADHD had unexpectedly low iPTH levels. Middle East, South-East Asian or African ethnic origin, being a young male and having a diagnosis of autism spectrum disorder or schizophrenia predicted low 25-OHD levels. Hence, the diagnoses that have been hypothetically linked to developmental (prenatal) vitamin D deficiency, schizophrenia and autism, had the lowest 25-OHD levels in this adult sample, supporting the notion that vitamin D deficiency may not only be a predisposing developmental factor but also relate to the adult patients' psychiatric state. This is further supported by the considerable psychiatric improvement that coincided with vitamin D treatment in some of the patients whose deficiency was treated.

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