Significant sex differences exist in the activity of the hypothalamic-pituitary-adrenal (HPA) axis. These differences are thought to contribute to the disparity in the prevalence of various autoimmune and infectious diseases between males and females. We use a mathematical model of the HPA axis to evaluate the hypothesis that differential sensitivity and negative feedback of the HPA axis network are causal factors for the observed sex differences in its activity. In doing so, we implicitly account for the differential influence of gonadal hormones on the HPA axis. Furthermore, we determine whether the putative mechanisms responsible for differences in basal HPA axis activity might also contribute to the observed differences in its stimulus-driven response. Model simulations predict the female HPA axis has greater adrenal sensitivity and weaker negative feedback. We identify two distinct sex-specific parameter spaces that generate corticosterone profiles in qualitative agreement with experimental results. We propose that these parameter sub-spaces are indicative of the inter-individual variability in the regulatory mechanisms of the HPA axis. Furthermore, the model predicts that the maintenance of homeostatic rhythms in response to chronic stress requires specific regulatory adaptations resulting in a phenotype of allostatically-driven chronic stress-sensitization. We propose these adaptations are indicative of a physiological cost of adaptation to chronic stress. Model simulations suggest that individuals with high adrenal sensitivity are more vulnerable to chronic stress sensitization and might be more susceptible to the development of neuropsychiatric disorders. These results contribute to the study of sex differences in physiological feedback systems within a quantitative framework.
This research output has an Altmetric Attention Score of 6. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 02 July 2018.
All research outputs
#7,113,466
of 27,267,055 outputs
Outputs from Endocrinology
#2,800
of 12,113 outputs
Outputs of similar age
#94,666
of 329,925 outputs
Outputs of similar age from Endocrinology
#7
of 89 outputs
Altmetric has tracked 27,267,055 research outputs across all sources so far. This one has received more attention than most of these and is in the 73rd percentile.
So far Altmetric has tracked 12,113 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.5. This one has done well, scoring higher than 76% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 329,925 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 71% of its contemporaries.
We're also able to compare this research output to 89 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 92% of its contemporaries.
