Androgen receptor (AR) is reactivated in castration-resistant prostate cancer (CRPC) through mechanisms including marked increases in AR gene expression. We identify an enhancer in the AR second intron contributing to increased AR expression at low androgen levels in CRPC. Moreover, at increased androgen levels, the AR binds this site and represses AR gene expression through recruitment of lysi...

OBJECTIVE To relate the repeat length of the androgen-receptor CAG trinucleotide to the age of onset of prostate cancer, stage and grade of disease. PATIENTS AND METHODS After obtaining ethical approval, 265 patients with locally confined or locally advanced/metastatic prostate cancer were identified and evaluated for age at diagnosis (< 65 years and > 75 years). DNA was extracted from periph...

Prostate cancers (PCas) become resistant to hormone withdrawal through increased androgen receptor (AR) signaling. Here we show increased AR-mediated transcription efficiency in PCa cells that have acquired the ability to grow in low concentrations of androgen. Compared to androgen-dependent PCa cells, these cells showed increased activity of transiently transfected reporters and increased mRNA...

Kennedy's disease is a degenerative disease of motor neurons in which the causative mutation is expansion of a CAG/polyglutamine tract near the 5' end of the androgen receptor gene. The mutant protein misfolds, aggregates, and interacts abnormally with other proteins, leading to a novel, toxic gain of function and an alteration of normal function. We used a cell culture model to explore the mec...

The spinal nucleus of the bulbocavernosus (SNB) and its target muscles, bulbocavernosus and levator ani (BC/LA), form a sexually dimorphic neuromuscular circuit whose development and maintenance are androgen-dependent. The mechanisms whereby androgen regulates gene expression in the SNB of adult rats are largely unknown, although a retrograde influence from the BC/LA muscles has been suggested ...

Autoregulation is a control mechanism common to several proteins of the steroid/thyroid hormone receptor superfamily. In this work, the effect of androgens and antiandrogens on the expression of the human androgen receptor (hAR) in prostate and breast cancer cell lines was studied. Northern blot analysis revealed a decrease in hAR steady state RNA levels in LNCaP cells by 3.3 nM of the syntheti...

background: to evaluate vdr gene variation and its interaction with immune regulatory molecules in osteoporosis. methods: totally 205 pre and postmenopausal women were recruited in the study. after an overnight fast, peripheral blood was taken and centrifuged to sprat serum for measurement of serum parathyroid hormone, 25 hydroxyvitamin d, osteocal­cin and cross laps. the fok i polymorphism in ...

BACKGROUND The androgen insensitivity syndrome (AIS) is a disease connected with the inactivation of AR due to a mutation that inactivate male sexual differentiation, and causes a spectrum of phenotypic anomalies having as a common aspect the loss of reproductive characteristics. PATIENTS In this paper the clinical, endocrinological and molecular features of three patients are reported. The f...

amyotrophic lateral sclerosis (als) is a progressive neurodegenerative disorder of the motor neurons in the spinal cord, brainstem, and motor cortex. ten percent of als cases are familial with both autosomal dominant and recessive modes of inheritance. mutations in the copper/zinc superoxidedismutase-1 (sod-1) gene, the first gene linked with als, result in sod-1 gene accounting for ~ 20% of fa...

In the present study, the role of BRCA1 in ligand-dependent androgen receptor (AR) signaling was assessed. In transfected prostate and breast cancer cell lines, BRCA1 enhanced AR-dependent transactivation of a probasin-derived reporter gene. The effects of BRCA1 were mediated through the NH2-terminal activation function (AF-1) of the receptor. Cotransfection of p160 coactivators markedly potent...