Variation of the epidermal expression of glucocorticoid receptor-beta as potential predictive marker of bullous pemphigoid outcome

2017 ◽  
Vol 26 (12) ◽  
pp. 1261-1266 ◽  
Author(s):  
Adrien Brulefert ◽  
Sébastien Le Jan ◽  
Julie Plée ◽  
Anne Durlach ◽  
Philippe Bernard ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Bullous Pemphigoid ◽  
Predictive Marker ◽  
Epidermal Expression ◽  
Glucocorticoid Receptor Beta ◽  
Receptor Beta

scholarly journals Glucocorticoid Receptor Beta and Its Prognostic Value on Treatment Response in Chronic Vulvar Dermatitis

2021 ◽  
pp. 1-8
Author(s):  
Valerie Bernays ◽  
Mariusz Pawel Kowalewski ◽  
Ioannis Dedes ◽  
Katrin Kerl French ◽  
Daniel Fink ◽  
...  
Keyword(s):  
Cohort Study ◽  
Glucocorticoid Receptor ◽  
Treatment Response ◽  
Retrospective Cohort ◽  
Prognostic Value ◽  
Biological Data ◽  
Topical Glucocorticoids ◽  
Prevalent Disease ◽  
Glucocorticoid Receptor Beta ◽  
Receptor Beta

<b><i>Background:</i></b> Chronic vulvar dermatitis (CVD) is the most prevalent disease in gynecologic dermatology. The treatment mainly depends on topical glucocorticoids (TGC) but is challenged by insufficient treatment response. On a histological level, the upregulation of the glucocorticoid receptor β (GRβ), an inhibitor of the active glucocorticoid receptor α (GRα), is discussed as mechanism of glucocorticoid insensitivity. <b><i>Objectives:</i></b> To analyze whether the expression of GRβ protein at baseline in keratinocytes may predict responsiveness to TGC in patients with CVD. <b><i>Methods:</i></b> In this retrospective cohort study, clinical and biological data of 25 women with a histological diagnosis of chronic vulvar eczema were analyzed. Randomization was done according to the responsiveness to TGC treatment (responsive vs. nonresponsive). Clinical data and the expression of GRβ in the immunohistochemical stained biopsies were examined. <b><i>Results:</i></b> Fifty-two percent of women with CVD were nonresponsive to TGC. GRβ was abundantly expressed in the cytoplasma of keratinocytes of the vulvar epithelium, but no difference in the level of expression was found among GC responsive and nonresponsive patients in the semiquantitative (<i>p</i> = 0.376) and quantitative analysis (<i>p</i> = 0.894). <b><i>Conclusion:</i></b> GRβ is highly expressed in keratinocytes of the vulvar epidermis affected by CVD, but GRβ expression was not increased in patients nonresponsive to TGC compared to responsive patients. Thus, the failure mechanism in nonresponders still remains to be elucidated.

scholarly journals Molecular Origins for the Dominant Negative Function of Human Glucocorticoid Receptor Beta

2003 ◽  
Vol 23 (12) ◽  
pp. 4319-4330 ◽  
Author(s):  
Matthew R. Yudt ◽  
Christine M. Jewell ◽  
Rachelle J. Bienstock ◽  
John A. Cidlowski
Keyword(s):  
Glucocorticoid Receptor ◽  
Dominant Negative ◽  
Critical Feature ◽  
Negative Function ◽  
Helix 12 ◽  
Sequential Mutagenesis ◽  
Dominant Negative Activity ◽  
Glucocorticoid Receptor Beta ◽  
Receptor Beta ◽  
Negative Phenotype

ABSTRACT This study molecularly elucidates the basis for the dominant negative mechanism of the glucocorticoid receptor (GR) isoform hGRβ, whose overexpression is associated with human glucocorticoid resistance. Using a series of truncated hGRα mutants and sequential mutagenesis to generate a series of hGRα/β hybrids, we find that the absence of helix 12 is neither necessary nor sufficient for the GR dominant negative phenotype. Moreover, we have localized the dominant negative activity of hGRβ to two residues and found that nuclear localization, in addition to heterodimerization, is a critical feature of the dominant negative activity. Molecular modeling of wild-type and mutant hGRα and hGRβ provides structural insight and a potential physical explanation for the lack of hormone binding and the dominant negative actions of hGRβ.

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