Glucocorticoid sensitivity may increase risk for stress-related diseases
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Healthy adults with the highest sensitivity to glucocorticoids have a proteomic profile suggesting a greater capability for responding to stressful stimuli compared with those with lowest sensitivity, according to study data.
At the same time, adults with high glucocorticoid sensitivity may be at increased risk for stress-related diseases, including myocardial infarction, according to Nicolas C. Nicolaides, MD, PhD, academic scholar and pediatric endocrinology fellow at the National and Kapodistrian University of Athens Medical School and Aghia Sophia Children's Hospital.
“We speculate that if the most glucocorticoid-sensitive subjects are exposed to excessive or prolonged stress, the extreme platelet activation could predispose to clot formation in the heart and brain, leading to infarctions,” Nicolaides told Healio.
The findings were presented at the European Society for Pediatric Endocrinology virtual meeting.
Nicolaides and colleagues measured 8 a.m. serum cortisol concentrations of 101 healthy volunteers following a 0.25 mg dose of dexamethasone at midnight. Researchers identified 11 participants with the lowest cortisol concentrations as the glucocorticoid sensitive group and 11 with the highest concentrations as the glucocorticoid resistant group. None of the 22 participants had any genetic defect in the NR3C1 gene. Both the glucocorticoid sensitive and resistant groups had plasma samples collected at 1 month, and proteomic profiles were analyzed through liquid chromatography-mass spectrometry.
The glucocorticoid sensitive group had 110 upregulated proteins compared with the glucocorticoid resistant group, whereas 66 proteins were found to be more abundant in the resistant cohort; 11 proteins were present in only the glucocorticoid resistant group and nine found only in the glucocorticoid sensitive group. Most of the upregulated proteins in the glucocorticoid sensitive group involved platelet activation and erythrocyte gas exchange.
“It was really surprising to find proteins involved in erythrocyte gas exchange and platelet activation in the most glucocorticoid-sensitive subjects, because they were healthy participants without any known stress-related health problems,” Nicolaides said. “It seems that this group of participants is more capable to cope with any stressors. On the other hand, if these subjects face chronic stress, they have higher risk of infarctions due to increased platelet activity.”
A random forest classifier was created using proteomics data to separate glucocorticoid-sensitive participants from those who were glucocorticoid resistant. In the classifier, the proteins apolipoprotein A4 and gelsolin were identified as the most important variables.
Nicolaides noted the findings are the third part of a larger project examining differences in tissue sensitivity to glucocorticoids in healthy people.
“We have recently published our findings on transcriptomics and metabolomics analyses in healthy subjects with differences in tissue sensitivity to glucocorticoids, which have also been presented at previous ESPE annual meetings,” Nicolaides said. “Our next step is to undertake larger studies in order to elucidate further the role of omics’ analysis in determining tissue sensitivity to glucocorticoids in healthy subjects.”
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Nicolaides NC, et al. P1-106. Presented at: European Society for Pediatric Endocrinology Annual Meeting; Sept. 22-26, 2021 (virtual meeting).
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