Sex differences in hypothalamic-pituitary-adrenal axis regulation after chronic unpredictable stress.
INTRODUCTION
Exposure to stress, mediated through the hypothalamic-pituitary-adrenal (HPA) axis, elicits sex differences in endocrine, neurological, and behavioral responses. However, the sex-specific factors that confer resilience or vulnerability to stress and stress-associated psychiatric disorders remain largely unknown. The evident sex differences in stress-related disease prevalence suggest the underlying differences in the neurobiological underpinnings of HPA axis regulation.


METHOD
Here, we used a chronic unpredictable stress (CUS) model to investigate the behavioral and biochemical responses of the HPA axis in C57BL/6 mice. Animals were tested in the open field and forced swim test to examine anxiety-like and depressive-like behaviors. Plasma corticosterone levels were measured after behavior and CUS, and glucocorticoid receptor (GR) expression and cytosolic and nuclear fractions of binding protein FKBP51 expression were taken to measure function and regulation of the stress response.


RESULTS
Our results indicate increased depressive-like behavior in males and females which correlated with increased corticosterone levels following CUS. However, females displayed more anxiety-like behaviors with and without CUS. Interestingly, we found trends toward dysregulation of GR protein expression in CUS females, and an increase in the GR inhibitory protein, FKBP51, in the cytosol of CUS males but not females.


CONCLUSION
These results suggest biochemical alterations to the HPA axis regulation which may elicit a glucocorticoid resistance in females after chronic stress and may contribute to the sex-biased vulnerability to stress-related psychiatric disorders.
['Palumbo|Michelle C|MC|0000-0003-2910-7170', 'Dominguez|Sky|S|', 'Dong|Hongxin|H|']
D000818:Animals D001007:Anxiety D001522:Behavior, Animal D003345:Corticosterone D003863:Depression D005260:Female D007030:Hypothalamo-Hypophyseal System D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D010913:Pituitary-Adrenal System D011965:Receptors, Glucocorticoid D012737:Sex Factors D013315:Stress, Psychological D022021:Tacrolimus Binding Proteins
sex differences HPA axis glucocorticoid receptor FKBP51 chronic stress