The study aimed to
create a test that could differentiate between stress hormone sensitive and
resistant people, to help clinicians better determine therapeutic outcomes and
minimise adverse effects in those requiring glucocorticoid treatment.
Interestingly, the protein profile associated with glucocorticoid sensitivity
included increased risk markers of stress-related disorders such as stroke and
heart attack, and may point to new possibilities for diagnostics or therapy in
these areas.
Glucocorticoids (GCs) are a group of hormones produced
naturally in the body, one of which is the stress hormone cortisol, and they
are essential for metabolism and healthy immune function. They act as
anti-inflammatories and are routinely used to treat allergies, asthma and other
conditions involving an overactive immune system. However, people respond
differently to GCs. A test distinguishing between sensitive and resistant
people would be very useful in improving treatment outcomes. Proteins in our
body are responsible for recognising, transporting and effecting the actions of
hormones such as GCs, so it may be that the protein profiles of sensitive and
resistant people could indicate GC effectiveness. Chronic stress has long been
associated with an increased risk of developing heart disease and stroke but
the underlying physiological changes are not well understood.
In this study, Dr Nicolas Nicolaides and colleagues in Athens, Greece, investigated
whether a set of proteins could be identified that would distinguish between GC
sensitive and resistant people. 101 healthy volunteers were given a low dose of
the GC, dexamethasone, then ranked from the most sensitive to most resistant,
based on their blood cortisol levels the following morning. Samples from the
top and bottom 10% were then analysed using liquid chromatography mass
spectrometry to identify differences in the protein profile between these
groups. The sensitive group had 110 upregulated and 66 downregulated proteins
compared with the resistant group. Of the upregulated proteins in the sensitive
group, several were associated with enhanced blood clotting, amyloid plaque
formation in Alzheimer’s disease and immune function.
Dr Nicolaides states, Our findings show, for the first time, how increased glucocorticoid sensitivity may be associated with stress-related disorders, including
myocardial and brain infarctions, which could lead to new therapeutic interventions.“
Although Dr Nicolaides, cautions, “This was a small, study, so further, larger studies are
needed to confirm the differences observed between the glucocorticoid-sensitive
and resistant people.”
This study was part of a larger project, involving genetic and metabolic analyses in healthy subjects
with differences in tissue sensitivity to glucocorticoids. The team now plan to perform larger studies to confirm these findings and
develop a signature profile for identifying these patient groups, which may
also have increased susceptibility to stress-related disorders.
Dr Nicolaides comments, “We speculate that
if the most glucocorticoid sensitive people are exposed to excessive or prolonged stress,
the resultant increased blood cell activation could predispose them to clot formation in the
heart and brain, leading to heart attacks or strokes. We could potentially identify
those at more risk and in need of stress management."
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