Date of Award
5-2025
Document Type
Honors Thesis
Degree Name
Bachelor of Science
Department
Biological Science
Advisor/Committee Chair
Damian Zuloaga
Committee Member
Caroline Cartier
Abstract
The hypothalamic-pituitary adrenal (HPA)-axis is the body’s main neuroendocrine mechanism for regulating stress. It has been shown in both animal and human models that anxiety and depression like behavior is more prevalent in females compared to males. Studies have shown evidence that suggests there are sex differences in the HPA-axis that likely contribute to the observed sex difference. It has been shown that anxiety related behavior and HPA-axis responsiveness is correlated with androgens acting on androgen receptors (AR). The role of androgens acting on AR has a more unclear role in stress behavior and HPA-axis regulation when subjected to chronic stress conditions. In the first experiment presented, we attempted to probe the role androgens acting on androgen receptors have in affecting stress behavior and HPA-axis regulation. To achieve this, we induced chronic stress by utilizing a sub chronic variable stress (SCVS) paradigm in an experimental group of gonadectomized (GDX) mice with a dihydrotestosterone (DHT) pellet as well as a control group of GDX mice with a blank pellet. DHT is an androgen that preferentially binds AR and cannot be aromatized into an estrogen. We analyzed the results of this experiment based on comparison of behavioral analysis, measures of blood corticosterone (cort) levels, and brain cell quantification of regions of the brain associated with the stress response. The neural marker c-Fos was utilized for brain cell quantification, higher levels of c-Fos activation would be indicative of a higher level of stress in the associated brain regions. The findings of our experiment show that repeated stress did have an effect on behavior and did increase c-Fos activation in certain regions of the brain such as the CA1 region of the hippocampus. This suggests that androgens binding to androgen receptors can decrease the stress response when subjected to repeated stressors and may be responsible for the observed sex difference. HPA-axis activity has also been shown to be regulated by corticotropin releasing factor (CRF) binding to distinct receptors CRF receptor 1 (CRFR1) and CRF receptor 2 (CRFR2). CRFR1 jump starts the HPA axis response to stress, while CRFR2 plays an opposing role by lessening the stress response. Previous studies utilizing chronic variable stress (CVS) paradigms found CRFR1 to play a role in the etiology of these disorders and the observed sex difference. The aim of the second study in this paper was to induce CVS and look more closely at the involvement of CRFR2. For this, both male and female mice were split into an experimental CVS group and a control nonstress group and compared following their respective paradigm based on behavioral analysis, cort level, and brain cell quantification across regions of the brain associated with the stress response by looking at c-Fos and CRFR2 activation. Having more stress-activated CRFR2 is indicative of being better adapted for responding to stressors. Overall, we found a sex difference observed in the number of CRFR2 cells and the stress-activation of c-Fos cells in the brain associated with the stress response that suggests evidence for CRFR2 playing a role in the observed sex difference of males having lower rates of anxiety and depression than females.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Reilly, David, "Regulation of the Hypothalamic-Pituitary-Adrenal Axis Through Corticotropin-Releasing Factor Receptor 2 Activation and Androgens Acting on Androgen Receptors in Mice Exposed to Repeat Stress Conditions" (2025). Biological Sciences. 106.
https://scholarsarchive.library.albany.edu/honorscollege_biology/106
