Date of Award
Bachelor of Science
Differences in the prevalence of stress-related disorders between males and females, such as anxiety and depression, are believed to be partly due to sexually dimorphic brain structures, particularly those that regulate the hypothalamic-pituitary-adrenal (HPA) axis. Within the hypothalamus, the paraventricular nucleus (PVN) is a primary structure in the integration of many hormonal inputs and induces the release of corticotrophin-releasing factor (CRF), the primary regulator of the HPA axis as well as behavioral stress responses. A sex difference in the distribution of corticotrophin-releasing factor receptor 1 (CRFR1) containing cells in the PVN has been reported with more in male than in female mice. A previous study performed in our lab shows an adult gonadectomy causes a significant decrease in CRFR1 expressing cells in males, but not in females suggesting a possible mechanism in which gonadal hormones regulate CRFR1 expression. Androgen receptors show high co-expression with CRFR1 and are generally thought to play a role in the downregulation of the stress response and the HPA-axis although the mechanisms are widely unknown. The goal of this study was to gain insight into the role of androgens and potential receptors they may act on within the PVN and related sexually dimorphic structures to produce a sex difference in regulation of the stress response. Specifically, experiments were performed in mice to determine whether androgens, acting through the androgen receptor, regulate CRFR1 expression in the PVN as well as other key CRFR1 cell populations such as the bed nucleus of the stria terminalis (BST). We also determined if alteration of androgen treatment will alter the stress-induced activation of the CRFR1 neurons by having a down-regulation effect. Results from this experiment showed that gonadectomized animals showed a decrease in CRFR1 cell populations in the PVN that was reversed by the addition of dihydrotestosterone (DHT), an androgen that preferentially binds the androgen receptor. In the BSTld there was a decrease in CRFR1 in the GDX-DHT group when compared to GDX-blank and control sham operated groups. No significant findings were reported in the BSTav. Results also showed no differences in neural activation of CRFR1 neurons in the BSTld, BSTav or PVN with addition of DHT. Discovery of the mechanisms in which androgens regulate stress systems in the brain will help us gain a better understanding of why females develop stress-related disorders twice as frequently as males.
Sturm, Kassandra, "The Role of Androgens on Sexually Dimorphic Distributions of Key Corticotropin- Releasing Factor Receptor 1 Populations and Stress Responses within the Brain" (2021). Biological Sciences. 74.
Available for download on Wednesday, December 01, 2021