71 - Sex Differences in HPA-Axis Regulation: The Role of Gonadal Hormones

Abstract

One of the primary physiological consequences of life stress is activation of the hypothalamic–pituitary–adrenal axis (HPA axis). The HPA axis is a well-tuned system designed to achieve and maintain homeostasis. Activation of this system sets in motion a cascade of hormonal responses that allow the body to adapt to the stressor at hand. As with many physiological systems, there are sex differences in HPA-axis regulation across species. Understanding the nature of this sex difference is important, given that HPA-axis dysregulation is associated with a number of pathologies with significant female bias, including depression, anxiety, and autoimmune diseases. This chapter focuses on the role of gonadal hormones as modulators of HPA-axis function in animal models. We first discuss the contribution of gonadal hormones on the neuroendocrine and central responses to acute and chronic stress. Because gonadal hormones interact with specific receptors in target areas to produce their effects on HPA-axis tone, we also discuss the importance of steroid receptors in mediating these sex differences in HPA-axis activity. Finally, we summarize the current state of knowledge on neural control of gonadal hormone effects on HPA-axis regulation.