Endocrine Abstracts

The ‘Nuclear Receptor (NR) Super-family’ is a group of ligand modulated transcription factors with 48 members presently identified in human genome. NRs regulate most of the physiological processes of the body ranging from metabolism to reproduction. Retinoid X Receptor (RXR) is one of the important members of this NR superfamily. It serves as a heterodimeric partner of several other members of this superfamily including two major xenobiotic nuclear receptors i.e. Pre...

The corepressor NCOR2/SMRT regulates multiple nuclear receptors (NRs) and other transcription factors. Disruption to these functions are implicated in prostate cancer (PCa) progression but the details remain enigmatic. Therefore we sought to define the global functions of NCOR2/SMRT using isogenic PCa cell models, PCa mouse models and human PCa cohorts.We mapped the NCOR2 dependent transcriptome (RNA-seq), miRnome (miRNA-seq), methylome (EPIC methylation...

The importance of the Liver X receptors (LXRs) as a critical modulators of metabolic homeostasis and immunity in health and disease has been mainly gleaned from studies evaluating the consequences of their pharmacological or genetic manipulation. We previously showed LXRα is phosphorylated upon cholesterol loading. It is however unknown whether post-translational modifications of the receptor modulate diet-induced responses and affect metabolic diseases with an important ...

Resistance to newly developed androgen receptor pathway inhibitors (ARPIs), such as abiraterone and enzalutamide, rapidly emerges and patients generally die within 2 years. In particular, a subset of patients who relapse following ARPI therapy exhibit lineage switching whereby tumours shed their dependence on AR signaling and emerge with neuroendocrine features. These tumours, termed treatment induced neuroendocrine prostate cancer (t-NEPC), carry an extremely poor prognosis a...

The defining feature of endometriosis is that endometrial tissues are deposited and grown onto sites outside of the uterine cavity. The pathogenesis of endometriosis, however, remains controversial despite extensive research. Since the endometriosis has been known as an estrogen-dependent inflammatory disease, the alterations in estrogen-mediated cellular signaling play an essential role in the pathogenesis of endometriosis. In addition to higher estrogen receptor (ER)β l...

Glucocorticoids (GC) are catabolic in skeletal muscle to provide nutrients during fasting or other stressors, including inhibiting insulin-mediated glucose uptake, protein synthesis, and mitochondrial function, while stimulating proteosomal breakdown of proteins. Published work in cultured myotubes required μM GC dosing to see these effects. We found GCs to show low nM activity in myotubes by using a more physiologically relevant setting, including nutrient deprivation an...

It has long been known that the AR is regulated not only by its cognate steroid hormone, but also by interactions with a constellation of co-regulatory and signaling molecules. Checkpoint kinase 2 (CHK2) is a serine/threonine protein kinase whose main function is regulating the DNA damage response (DDR) triggered by double-strand DNA breaks. The androgen receptor (AR) is a major driver of prostate cancer, even at the castration–resistant stage of the disease. Our research...

Like other steroid hormone receptors (SHRs), the ERR binds to IR3 response elements (REs). However, the naturally occurring ERR binding sites are composed of single, extended half-sites (ERREs) that are recognized by the homodimeric ERR. In order to unravel the specific structural reasons and the related functional consequences related to the binding of a homodimer to single extended half-site REs, we conducted a series of complementary structural and biophysical experiments a...