Comparative analysis of the influence of the high-mobility group box 1 protein on DNA binding and transcriptional activation by the androgen, glucocorticoid, progesterone and mineralocorticoid receptors

2001 ◽  
Vol 361 (1) ◽  
pp. 97-103 ◽  
Author(s):  
Guy VERRIJDT ◽  
Annemie HAELENS ◽  
Erik SCHOENMAKERS ◽  
Wilfried ROMBAUTS ◽  
Frank CLAESSENS
Keyword(s):  
Androgen Receptor ◽  
Comparative Analysis ◽  
Dna Binding ◽  
Mineralocorticoid Receptor ◽  
Hormone Receptors ◽  
Steroid Hormone ◽  
High Mobility ◽  
Steroid Hormone Receptors ◽  
High Mobility Group ◽  
Mineralocorticoid Receptors

We performed a comparative analysis of the effect of high-mobility group box protein 1 (HMGB1) on DNA binding by the DNA-binding domains (DBDs) of the androgen, glucocorticoid, progesterone and mineralocorticoid receptors. The affinity of the DBDs of the different receptors for the tyrosine aminotransferase glucocorticoid response element, a classical high-affinity binding element, was augmented up to 7-fold by HMGB1. We found no major differences in the effects of HMGB1 on DNA binding between the different steroid hormone receptors. In transient transfection assays, however, HMGB1 significantly enhances the activity of the glucocorticoid and progesterone receptors but not the androgen or mineralocorticoid receptor. We also investigated the effect of HMGB1 on the binding of the androgen receptor DBD to a subclass of directly repeated response elements that is recognized exclusively by the androgen receptor and not by the glucocorticoid, progesterone or mineralocorticoid receptor. Surprisingly, a deletion of 26 amino acid residues from the C-terminal extension of the androgen receptor DBD does not influence DNA binding but destroys its sensitivity to HMGB1. Deletion of the corresponding fragment in the DBDs of the glucocorticoid, progesterone and mineralocorticoid receptor destroyed their DNA binding. This 26-residue fragment is therefore essential for the influence of HMGB1 on DNA recognition by all steroid hormone receptors that were tested. However, it is dispensable for DNA binding by the androgen receptor.

The androgen receptor DNA-binding domain determines androgen selectivity of transcriptional response

2006 ◽  
Vol 34 (6) ◽  
pp. 1089-1094 ◽  
Author(s):  
G. Verrijdt ◽  
T. Tanner ◽  
U. Moehren ◽  
L. Callewaert ◽  
A. Haelens ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Dna Binding ◽  
Cellular Response ◽  
Hormone Receptors ◽  
Target Genes ◽  
Steroid Hormone ◽  
Prostate Gland ◽  
Steroid Hormone Receptors ◽  
Binding Motif

The AR (androgen receptor) is a hormone-dependent transcription factor that translates circulating androgen hormone levels into a physiological cellular response by directly regulating the expression of its target genes. It is the key molecule in e.g. the development and maintenance of the male sexual characteristics, spermatocyte production and prostate gland development and growth. It is also a major factor in the onset and maintenance of prostate cancer and a first target for pharmaceutical action against the further proliferation of prostate cancer cells. The AR is a member of the steroid hormone receptors, a group of steroid-inducible transcription factors sharing an identical consensus DNA-binding motif. The problem of how specificity in gene activation is achieved among the different members of this nuclear receptor subfamily is still unclear. In this report, we describe our investigations on how the AR can specifically activate its target genes, while the other steroid hormone receptors do not, despite having the same consensus monomeric DNA-binding motif. In this respect, we describe how the AR interacts with a newly identified class of steroid-response elements to which only the AR and not, for example, the glucocorticoid receptor can bind.

scholarly journals Differential Responses to Steroid Hormones in Fibroblasts From the Vocal Fold, Trachea, and Esophagus

Endocrinology ◽  
2015 ◽  
Vol 156 (3) ◽  
pp. 1000-1009 ◽  
Author(s):  
Shigeyuki Mukudai ◽  
Ken Ichi Matsuda ◽  
Takeshi Nishio ◽  
Yoichiro Sugiyama ◽  
Hideki Bando ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Steroid Hormones ◽  
Vocal Fold ◽  
Hormone Receptors ◽  
Steroid Hormone ◽  
Vocal Folds ◽  
Steroid Hormone Receptors ◽  
Male Rats ◽  
Target Cells ◽  
Cultured Fibroblasts

Abstract There is accumulating evidence that fibroblasts are target cells for steroids such as sex hormones and corticoids. The characteristics of fibroblasts vary among tissues and organs. Our aim in this study is to examine differences in responses to steroid hormones among fibroblasts from different cervicothoracic regions. We compared the actions of steroid hormones on cultured fibroblasts from the vocal folds, which are considered to be the primary target of steroid hormones, and the trachea and esophagus in adult male rats. Expression of steroid hormone receptors (androgen receptor, estrogen receptor α, and glucocorticoid receptor) was identified by immunofluorescence histochemistry. Androgen receptor was much more frequently expressed in fibroblasts from the vocal fold than in those from the trachea and esophagus. Cell proliferation analysis showed that administration of testosterone, estradiol, or corticosterone suppressed growth of all 3 types of fibroblasts. However, mRNA expression for extracellular matrix–associated genes, including procollagen I and III and elastin, and hyaluronic acid synthase I was elevated only by addition of testosterone to fibroblasts from the vocal fold. These results indicate that each steroid hormone exerts region-specific effects on cervicothoracic fibroblasts with different properties through binding to specific receptors.

Molecular Biology of the Androgen Receptor

2002 ◽  
Vol 20 (13) ◽  
pp. 3001-3015 ◽  
Author(s):  
Edward P. Gelmann
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Ligand Binding ◽  
Dna Sequences ◽  
Hormone Receptors ◽  
Steroid Hormone ◽  
Three Dimensional ◽  
Intramolecular Interactions ◽  
Steroid Hormone Receptors ◽  
Dimensional Structure

ABSTRACT: Androgen receptor (AR) is a member of the steroid hormone receptor family of molecules. AR primarily is responsible for mediating the physiologic effects of androgens by binding to specific DNA sequences that influence transcription of androgen-responsive genes. The three-dimensional structure of the AR ligand-binding domain has shown it is similar to other steroid hormone receptors and that ligand binding alters the protein conformation to allow binding of coactivator molecules that amplify the hormone signal and mediate transcriptional initiation. However, AR also undergoes intramolecular interactions that regulate its interactions with coactivators and influence its activity. A large number of naturally occurring mutations of the human AR gene have provided important information about AR molecular structure and intermolecular interactions. AR is also a critical mediator of prostate cancer promotion, conferring growth signals to prostate cancer cells throughout the natural history of the disease. Late-stage prostate cancer, unresponsive to hormonal deprivation, sustains AR signaling through a diverse array of molecular strategies. Variations in the AR gene may also confer genetic predisposition to prostate cancer development and severity. Further understanding of AR action and new strategies to interfere with AR signaling hold promise for improving prostate cancer therapy.

scholarly journals The Role of Steroid Hormone Receptors in Urothelial Tumorigenesis

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2155
Author(s):  
Hiroki Ide ◽  
Hiroshi Miyamoto
Keyword(s):  
Estrogen Receptor ◽  
Androgen Receptor ◽  
Glucocorticoid Receptor ◽  
Hormone Receptors ◽  
Steroid Hormone ◽  
Tumor Development ◽  
Estrogen Receptor Α ◽  
Estrogen Receptor Β ◽  
Steroid Hormone Receptors

Preclinical and/or clinical evidence has indicated a potential role of steroid hormone-mediated signaling pathways in the development of various neoplastic diseases, while precise mechanisms for the functions of specific receptors remain poorly understood. Specifically, in urothelial cancer where sex-related differences particularly in its incidence are noted, activation of sex hormone receptors, such as androgen receptor and estrogen receptor-β, has been associated with the induction of tumor development. More recently, glucocorticoid receptor has been implied to function as a suppressor of urothelial tumorigenesis. This article summarizes and discusses available data suggesting that steroid hormone receptors, including androgen receptor, estrogen receptor-α, estrogen receptor-β, glucocorticoid receptor, progesterone receptor and vitamin D receptor, as well as their related signals, contribute to modulating urothelial tumorigenesis.

Antiandrogens as environmental endocrine disruptors¤

1998 ◽  
Vol 10 (1) ◽  
pp. 105 ◽  
Author(s):  
W. R. Kelce ◽  
L. E. Gray ◽  
E. M. Wilson
Keyword(s):  
Androgen Receptor ◽  
Hormone Receptors ◽  
Steroid Hormone ◽  
Sex Differentiation ◽  
Environmental Chemicals ◽  
Steroid Hormone Receptors ◽  
Environmental Endocrine Disruptors ◽  
And Function

Steroid hormone receptors control fundamental events in embryonic development and sex differentiation through their function as ligand-inducible transcription factors. The consequences of disrupting these processes can be especially profound during development due to the crucial role hormones play in controlling transient and irreversible developmental processes. Several environmental chemicals, including metabolites of the fungicide vinclozolin and the pesticide DDT, disrupt male reproductive development and function by inhibiting androgen receptor mediated events. A variety of in vitro and in vivo approaches have been used to determine the molecular basis of environmental antiandrogen toxicity. These chemicals commonly bind androgen receptor with moderate affinity and act as antagonists by inhibiting transcription of androgen dependent genes.

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