Sex differences in the response to acute stress

Although it is known that there are sex differences in the activity of the hypothalamus-pituitary-adrenal (HPA) axis in rodents, we don't know whether this is a reflection of the different levels of circulating hormones or whether active forms of the hormones are produced in the brain in a process known as neurosteroidogenesis. A team of scientists at the University of Edinburgh and involving JBL Science's Dr. Andy Gill have investigated steroid formation in the brain in response to stress in rats and found pronounced sex differences.

Steroid hormones play a crucial role in regulating physiological responses to stress. Neuroactive steroids are metabolites of classical steroid hormones that exert effects on brain excitability, and the brain itself can produce neuroactive steroids from cholesterol or through the conversion of steroids that come from the gonads or adrenal gland. The response to stress is mediated by the HPA axis, which gives rise to elevated levels of steroid hormones, including cortisol (corticosteroid in rodents) in response to stressful events and situations.

In rodents, the normal levels of corticosterone are higher in females than males and there is also clear evidence for increased HPA activity following stress in female rodents. The current study measured the levels of a variety of neuroactive steroid hormones, including corticosterone, progesterone, pregnenolone and testosterone after a forced swimming stress in rats. We found increased levels of many steroids in the brain, compared to blood, and the increases were more pronounced in females.

Dr Gill said "The data indicated differences in the local generation of neurosteroids between sexes and in different areas of the brain as well. These neurosteroids may contribute to sex differences in the HPA axis response to stress and further suggest sex-specific expression of steroidogenic enzymes in the brain.

"The project was made possible through the development of a novel quantitative assay for a panel of neurosteroids. Crucially, the assay needed to be sensitive enough to detect low levels of these chemicals in different regions of a rats brain - so quite a small amount of tissue really.

"The assay was based on Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) analysis, which is the gold standard for quantitative analysis of small molecule metabolites."

The team’s paper, titled ‘Sex‐dependent changes in neuroactive steroid concentrations in the rat brain following acute swim stress’, is published in Journal of Neuroendocrinology and the link to record in the University of Lincoln's online repository is below.

For more details please contact Dr. Andy Gill.

Sze, Ying and Gill, Andrew and Brunton, Paula J. (2018) Sex-dependent changes in neuroactive steroid concentrations in the rat brain following acute swim stress. Journal of Neuroendocrinology . ISSN 1365-2826

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