Reduced glucocorticoid receptor protein expression in children with critical illness.

Background/aims: The diagnostic criteria for critical illness-related corticoid insufficiency (CIRCI) are not well established, particularly for children. In addition to alterations in adrenal function, cellular resistance to glucocorticoid action could contribute to CIRCI due to alterations in the functioning of the intracellular receptor protein for corticosteroids, the glucocorticoid receptor (GR).

Methods: We have therefore undertaken a pilot, prospective study to assess whether cellular GR activity can be measured in peripheral blood mononuclear cells (PBMCs) from critically ill children.

Effects of a salsa dance training on balance and strength performance in older adults.

Background: Deficits in static and particularly dynamic postural control and force production have frequently been associated with an increased risk of falling in older adults.

Objective: The objectives of this study were to investigate the effects of salsa dancing on measures of static/dynamic postural control and leg extensor power in seniors.

Methods: Twenty-eight healthy older adults were randomly assigned to an intervention group (INT, n = 14, age 71.

Basis for a Swiss perspective on fall prevention in vulnerable older people.

During the 20th century Switzerland, like many other Western countries, experienced significant ageing of the population over the age of 65. As the lifespan of the Swiss population increases, so does the prevalence of falls. A multiplicity of fall prevention programmes are available, but extracting their most effective components remains a challenge.

Effects of muscle fatigue on gait characteristics under single and dual-task conditions in young and older adults.

Background: Muscle fatigue and dual-task walking (e.g., concurrent performance of a cognitive interference (CI) while walking) represent major fall risk factors in young and older adults.

Targeted ablation reveals a novel role of FKBP52 in gene-specific regulation of glucocorticoid receptor transcriptional activity.

FKBP52 is a tetratricopeptide repeat (TPR) protein with peptidyl-prolyl isomerase activity and is found in steroid receptor complexes, including glucocorticoid receptor (GR). It is generally accepted that FKBP52 has a stimulatory effect on GR transcriptional activity. However, the mechanism by which FKBP52 controls GR is not yet clear, with reports showing effects on GR hormone-binding affinity and/or hormone-induced nuclear translocation.

Control of glucocorticoid and progesterone receptor subcellular localization by the ligand-binding domain is mediated by distinct interactions with tetratricopeptide repeat proteins.

The TPR proteins FKBP52, FKBP51, Cyp40, and PP5 are found in steroid receptor (SR) complexes, but their receptor-specific preferences and roles remain unresolved. We have undertaken a systematic approach to this problem by examining the contribution of all four TPRs to the localization properties of glucocorticoid (GR) and progesterone (PR) receptors. The GR of L929 cells was found in the cytoplasm in a complex containing PP5 and FKBP51, while the GR of WCL2 cells was nuclear and contained PP5 and FKBP52.

Coactivators and nuclear receptor transactivation.

A variety of coregulator proteins serve as partners for nuclear receptors orchestrating the molecular events required for receptor-dependent transcriptional regulation. Some coregulators directly interact with nuclear receptors and provide a platform for recruitment of other factors that provide distinct biochemical activities that influence transcriptional efficiency. Coregulators can influence chromatin structure and activity via direct modification of histone proteins or by facilitating ATP-dependent chromatin remodeling.

Glucocorticoid receptor physiology.

Glucocorticoid action in cells is mediated by a specific receptor protein, the glucocorticoid receptor (GR). GR is a member of a superfamily of ligand-inducible transcription factors that control a variety of physiological functions; such as, metabolism, development, and reproduction. Unliganded GR is predominantly localized within the cytoplasm but rapidly and efficiently translocates to the nucleus following hormone binding.

Essential role for Co-chaperone Fkbp52 but not Fkbp51 in androgen receptor-mediated signaling and physiology.

Fkbp52 and Fkbp51 are tetratricopeptide repeat proteins found in steroid receptor complexes, and Fkbp51 is an androgen receptor (AR) target gene. Although in vitro studies suggest that Fkbp52 and Fkbp51 regulate hormone binding and/or subcellular trafficking of receptors, the roles of Fkbp52 and Fkbp51 in vivo have not been extensively investigated. Here, we evaluate their physiological roles in Fkbp52-deficient and Fkbp51-deficient mice.

FK506-binding protein 52 is essential to uterine reproductive physiology controlled by the progesterone receptor A isoform.

FK506-binding protein 52 (FKBP52) is a tetratricopeptide repeat protein that associates with steroid receptors in complexes containing heat shock protein 90. To investigate the role of FKBP52 in steroid-regulated physiology, we generated FKBP52-deficient mice. FKBP52 (-/-) females are sterile due to a complete failure of implantation, a process that requires estrogen (ER) and progesterone receptors (PR).

Enhancement of glucocorticoid receptor-mediated gene expression by constitutively active heat shock factor 1.

To further define the role of heat shock factor 1 (HSF1) in the stress potentiation of glucocorticoid receptor (GR) activity, we placed a constitutively active mutant of human HSF1 (hHSF1-E189) under the control of a doxycycline (DOX)-inducible vector. In mouse L929 cells, DOX-induced expression of hHSF1-E189 correlated with in vivo occupancy of the human heat shock protein 70 (hHsp70) promoter (chromatin-immunoprecipitation assay) and with increased activity under nonstress conditions at the hHsp70 promoter controlling expression of chloramphenicol acetyl transferase (CAT) (p2500-CAT). Comparison of hHSF1-E189 against stress-activated, endogenous HSF1 for DNA-binding, p2500-CAT, and Hsp70 protein expression activities showed the mutant factor to have lower, but clearly detectable, activities as compared with wild-type factor.