Development of the HPA axis: where and when do sex differences manifest?

Sex differences in the response to stress contribute to sex differences in somatic, neurological, and psychiatric diseases. Despite a growing literature on the mechanisms that mediate sex differences in the stress response, the ontogeny of these differences has not been comprehensively reviewed. This review focuses on the development of the hypothalamic-pituitary-adrenal (HPA) axis, a key component of the body's response to stress, and examines the critical points of divergence during development between males and females. Insight gained from animal models and clinical studies are presented to fully illustrate the current state of knowledge regarding sex differences in response to stress over development. An appreciation for the developmental timelines of the components of the HPA axis will provide a foundation for future areas of study by highlighting both what is known and calling attention to areas in which sex differences in the development of the HPA axis have been understudied.