Posts tagged glucocorticoids
Articles and news from the latest research reports.
Biomarker Could Reveal Why Some Develop Post-Traumatic Stress Disorder
Blood expression levels of genes targeted by the stress hormones called glucocorticoids could be a physical measure, or biomarker, of risk for developing Post-Traumatic Stress Disorder (PTSD), according to a study conducted in rats by researchers at the Icahn School of Medicine at Mount Sinai and published August 11 in Proceedings of the National Academy of Sciences (PNAS). That also makes the steroid hormones’ receptor, the glucocorticoid receptor, a potential target for new drugs.
Post-Traumatic Stress Disorder (PTSD) is triggered by a terrifying event, either witnessed or experienced. Symptoms may include flashbacks, nightmares and severe anxiety, as well as uncontrollable thoughts about the event. Not everyone who experiences trauma develops PTSD, which is why the study aimed to identify biomarkers that could better measure each person’s vulnerability to the disorder.
“Our aim was to determine which genes are differentially expressed in relation to PTSD,” said lead investigator Rachel Yehuda, PhD, Professor of Psychiatry and Neuroscience and Director of the Traumatic Stress Studies Division at the Icahn School of Medicine at Mount Sinai. “We found that most of the genes and pathways that are different in PTSD-like animals compared to resilient animals are related to the glucocorticoid receptor, which suggests we might have identified a therapeutic target for treatment of PTSD,” said Dr. Yehuda, who also heads the Mental Health Patient Care Center and PTSD Research Program at the James J. Peters Veterans Affairs Medical Center in the Bronx.
The research team exposed a group of male and female rats to litter soiled by cat urine, a predatory scent that mimics a life-threatening situation. Most PTSD studies until now have used only male rats. Mount Sinai researchers included female rats in this study since women are more vulnerable than men to developing PTSD. The rats were then categorized based on their behavior one week after exposure to the scent. The authors also examined patterns of gene expression in the blood and in stress-responsive brain regions.
After one week of being exposed to soiled cat litter for 10 minutes, vulnerable rats exhibited higher anxiety and hyperarousal, and showed altered glucocorticoid receptor signaling in all tissues compared with resilient rats. Moreover, some rats were treated with a hormone that activates the glucocorticoid receptor called corticosterone one hour after exposure to the cat urine scent. These rats showed lower levels of anxiety and arousal one week later compared with untreated, trauma-exposed rats.
“PTSD is not just a disorder that affects the brain,” said co-investigator Nikolaos Daskalakis, MD, PhD, Associate Research Scientist in the Department of Psychiatry at the Icahn School of Medicine at Mount Sinai. “It involves the entire body, which is why identifying common regulators is key. The glucocorticoid receptor is the one common regulator that consistently stood out.”
(Image: photos.com)
Stress hormone receptors localized in sweet taste cells
According to new research from the Monell Center, receptors for stress-activated hormones have been localized in oral taste cells responsible for detection of sweet, umami, and bitter. The findings suggest that these hormones, known as glucocorticoids, may act directly on taste receptor cells under conditions of stress to affect how these cells respond to sugars and certain other taste stimuli.
"Sweet taste may be particularly affected by stress," said lead author M. Rockwell Parker, PhD, a chemical ecologist at Monell. "Our results may provide a molecular mechanism to help explain why some people eat more sugary foods when they are experiencing intense stress."
Glucocorticoid (GC) hormones affect the body by activating specialized GC receptors located inside of cells. Knowing that stress can have major effects on metabolism and food choice, the researchers used a mouse model to ask whether taste receptor cells contain these GC receptors.
The findings, published online ahead of print in the journal Neuroscience Letters, revealed that GC receptors are present on the tongue, where they are specifically localized to the cells that contain receptors for sweet, umami and bitter taste. The highest concentrations of GC receptors were found in Tas1r3 taste cells, which are sensitive to sweet and umami taste.
GC hormones act on cells via a multi-step process. After GCs bind to their receptors within target cells, the activated receptor complex moves, or translocates, to the cell nucleus, where it then influences gene expression and protein assembly.
To explore whether GC receptors in taste tissue are activated by stress, the researchers compared the proportion of taste cells with translocated receptors in stressed and non-stressed mice. Compared to controls, the stressed mice had a 77 percent increase of GC receptors within taste cell nuclei.
Together, the results suggest that sweet taste perception and intake, which are known to be altered by stress, may be specifically affected via secretion of GCs and subsequent activation of GC receptors in taste cells.
"Taste provides one of our initial evaluations of potential foods. If this sense can be directly affected by stress-related hormonal changes, our food interaction will likewise be altered," said Parker.
Parker noted that although stress is known to affect intake of salty foods, GC receptors were not found in cells thought to be responsible for detecting sally and sour taste. One explanation, he said, is that stress may influence salt taste processing in the brain.
Implications of the findings extend beyond the oral taste system. Noting that taste receptors are found throughout the body, senior author and Monell molecular neurobiologist Robert Margolskee, MD, PhD, said, “Taste receptors in the gut and pancreas might also be influenced by stress, potentially impacting metabolism of sugars and other nutrients and affecting appetite.”
Future studies will continue to explore how stress hormones act to affect the taste system.
(Source: eurekalert.org)
Exposure to Cortisol-Like Medications Before Birth May Contribute to Emotional Problems and Brain Changes
Neonatologists seem to perform miracles in the fight to support the survival of babies born prematurely.
To promote their survival, cortisol-like drugs called glucocorticoids are administered frequently to women in preterm labor to accelerate their babies’ lung maturation prior to birth. Cortisol is a substance naturally released by the body when stressed. But the levels of glucocorticoids administered to promote lung development are higher than that achieved with typical stress, perhaps only mirrored in the body’s reaction to extreme stresses.
The benefit of glucocorticoids is undisputed and has certainly saved the lives of countless babies, but this exposure also may have some negative consequences. Indeed, excessive glucocorticoid levels may have effects on brain development, perhaps contributing to emotional problems later in life.
In this issue of Biological Psychiatry, Dr. Elysia Davis at the University of Denver and her colleagues report new findings on the effects of synthetic glucocorticoid on human brain development. Their study focused on healthy children who were born full-term, avoiding the confounding effects of premature birth.
The investigators conducted brain imaging sessions in and carefully assessed 54 children, 6-10 years of age. The mothers of the participating children also completed reports on their child’s behavior. The researchers then divided the children into two groups: those who were exposed to glucocorticoids prenatally and those who were not.
In this study, children with fetal glucocorticoid exposure showed significant cortical thinning, and a thinner cortex also predicted more emotional problems. In one particularly affected part of the brain, the rostral anterior cingulate cortex, it was 8-9% thinner among children exposed to glucocorticoids. Interestingly, other studies have shown that this region of the brain is affected in individuals diagnosed with mood and anxiety disorders.
"Fetal exposure to a frequently administered stress hormone is associated with consequences for child brain development that persist for at least 6 to 10 years. These neurological changes are associated with increased risk for stress and emotional problems," Davis explained of their findings. "Importantly, these findings were observed among healthy children born full term."
Although such a finding does not indicate that glucocorticoids ‘caused’ these changes, the researchers did determine that the findings can’t be explained by any obvious confounding differences between the groups. The two groups did not differ on weight or gestational age at birth, apgar scores, maternal factors, or any other basic demographics. Thus, the findings do suggest that glucocorticoid administration may somehow alter the trajectory of brain development of exposed children.
"This study provides evidence that prenatal exposure to stress hormones shapes the construction of the fetal nervous system with consequences for the developing brain that persist into the preadolescent period," she added.
"This study highlights potential links between early cortisol exposure, cortical thinning and mood symptoms in children. It may provide important insights into the development of the brain and the long-term impact of maternal stress," commented Dr. John Krystal, Editor of Biological Psychiatry.
(Source: elsevier.com)