The glucocorticoid receptor (GR) is a constitutively expressed transcriptional regulatory factor (TRF) that controls many distinct gene networks, each uniquely determined by particular cellular and physiological contexts. The precision of GR-mediated responses seems to depend on combinatorial, context-specific assembly of GR-nucleated transcription regulatory complexes at genomic response elements. In turn, evidence suggests that context-driven plasticity is conferred by the integration of multiple signals, each serving as an allosteric effector of GR conformation, a key determinant of regulatory complex composition and activity. This structural and mechanistic perspective on GR regulatory specificity is likely to extend to other eukaryotic TRFs.
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http://dx.doi.org/10.1038/nrm.2016.152 | DOI Listing |
Zhong Nan Da Xue Xue Bao Yi Xue Ban
July 2024
Department of Endocrinology, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China.
Immune checkpoint inhibitors (ICPis) significantly improves survival in a number of cancer patients by blocking immunosuppressive molecules and reactivating the function of effector T cells to specifically kil tumor cells. This article reports a case of secondary hypoadrenocorticism caused by programmed death 1 (PD-1) inhibitor related hypophysitis. A 65-year-old male patient received immunotherapy for right lung squamous cell carcinoma invading the chest wall (cT4N2M0) for 4 times.
View Article and Find Full Text PDFZhong Nan Da Xue Xue Bao Yi Xue Ban
July 2024
Department of Endocrinology &Metabolism, West China Hospital, Sichuan University, Chengdu 610041.
Cushing's disease is a rare endocrine disorder characterized by hypercortisolism. Chronic elevated cortisol levels can lead to dysfunction or complications in multiple organs of systems, including cardiovascular, glucose, and bone metabolism, severely impacting patients' quality of life and posing life-threatening risks. Surgery is the first-line treatment for Cushing's disease.
View Article and Find Full Text PDFMol Metab
January 2025
Leibniz Institute for Resilience Research, 55122 Mainz Germany; Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, 55128 Mainz Germany. Electronic address:
Overconsumption of palatable food and energy accumulation are evolutionary mechanisms of survival when food is scarce. This innate mechanism becomes detrimental in obesogenic environment promoting obesity and related comorbidities, including mood disorders. The endocannabinoid system favors energy accumulation and regulates reward circuits.
View Article and Find Full Text PDFPNAS Nexus
January 2025
Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, 3501 Fifth Avenue, Pittsburgh, PA 15261, USA.
Bronchopulmonary dysplasia, the most prevalent chronic lung disease of prematurity, is often treated with glucocorticoids (GCs) such as dexamethasone (DEX), but their use is encumbered with several adverse somatic, metabolic, and neurologic effects. We previously reported that systemic delivery of the GC prodrug ciclesonide (CIC) in neonatal rats activated glucocorticoid receptor (GR) transcriptional responses in lung but did not trigger multiple adverse effects caused by DEX. To determine whether limited systemic metabolism of CIC was solely responsible for its enhanced safety profile, we treated neonatal rats with its active metabolite desisobutyryl-ciclesonide (Des-CIC).
View Article and Find Full Text PDFNeuroimage
January 2025
School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, China. Electronic address:
Background: Although epigenomic and environment interactions (Epigenome × Environment; Epi × E) might constitute a novel mechanism underlying reward processing direct evidence is still scarce. We conducted the first longitudinal study to investigate the extent to which DNA methylation of a stress-related gene-NR3C1-interacts with childhood maltreatment in association with young adult reward responsiveness (RR) and the downstream risk of depressive (anhedonia dimension in particular) and anxiety symptoms.
Method: A total of 192 Chinese university students aged 18∼25 (M = 21.
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