The blockade of glucocorticoid (GC) action through antagonism of the glucocorticoid receptor II (GRII) has been used to minimize the undesirable effects of chronically elevated GC levels. Mifepristone (RU486) is known to competitively block GRII action, but not exclusively, as it antagonizes the progesterone receptor. A number of new selective GRII antagonists have been developed, but limited t...

Stress is known to modulate sensitisation to repeated psychostimulant exposure. However, there is no direct evidence linking glucocorticoids and sensitisation achieved by repeated administration of the NMDA receptor antagonist MK-801. We tested the hypothesis that co-administration of RU486, a glucocorticoid receptor (GR) antagonist, prior to repeated daily MK-801 injections would block the exp...

Stress-like elevations in plasma cortisol suppress LH pulse amplitude in ovariectomized ewes by inhibiting pituitary responsiveness to GnRH. Here we sought to identify the receptor mediating this effect. In a preliminary experiment GnRH and LH pulses were monitored in ovariectomized ewes treated with cortisol plus spironolactone, which antagonizes the type I mineralocorticoid receptor (MR), or ...

The steroid compound cyproterone acetate was identified in a high-throughput screen for glucocorticoid receptor (GR) binding compounds. Cyproterone (Schering AG) is clinically used as an antiandrogen for inoperable prostate cancer, virilizing syndromes in women, and the inhibition of sex drive in men. Despite its progestin properties, cyproterone shares a similar pharmacological profile with th...

Glucocorticoids are widely administered for the treatment of various disorders, although their long-term use results in adverse effects associated with glucocorticoid excess. We investigated the pathophysiological roles of glucocorticoid receptors (GRs) and mineralocorticoid receptors (MRs) in the cardiac changes induced by exogenous corticosterone in rats. Corticosterone or vehicle was injecte...

Plasma corticosterone increases during spring migration in a variety of bird species, including the Gambel's white-crowned sparrow Zonotrichia leucophrys gambelii. Corticosterone is elevated specifically in association with migratory flight, suggesting that corticosterone may promote processes such as energy mobilization and/or migratory activity. General effects of glucocorticoids support such...

Administration of RU486 in vivo during the receptive phase rapidly renders the endometrium non-receptive to the implanting embryo. In order to identify key pathways responsible for endometrial receptivity we have used cDNA arrays to monitor gene expression changes in short-term endometrial explants in response to RU486. Endometrial biopsies from five normal fertile women at mid-secretory phase ...

Cortisol, the principal corticosteroid in teleosts, is thought to play a key role in the metabolic adjustments critical for regaining homeostasis. However, the target tissue molecular mechanisms involved in this adaptive response to corticosteroid stimulation are still unclear. Cortisol signaling is mediated predominantly by the glucocorticoid receptor (GR), and previous studies have shown that...

AIMS Stress mechanisms paradoxically contribute to allergic episodes in humans and mice. Glucocorticoids (GC) and interleukin (IL)-5 synergically upregulate murine bone-marrow eosinophil production. Here we explored the role of endogenous GC in allergen-stimulated bone-marrow eosinophil production in ovalbumin-sensitized/challenged mice. MAIN METHODS In BALB/c or C57BL/6 mice, sensitized and ...

Introduction: In explant cultures of human fetal membranes (FM) granulocyte-macrophage-colony-stimulating-factor (GM-CSF) mediates the inflammation-induced FM weakening seen in preterm premature rupture (pPROM) and exogenous progesterone (P4) inhibits GM-CSF weakening. Here we report that induces P4 production within which then acts a paracrine manner to counteract GM-CSF-induced Methods: expla...