Organizational effects of the neonatal testosterone surge on the hypothalamic-pituitary-adrenal axis

Mood disorders affect nearly 10 per cent of the population globally and have an enormous impact on society as a whole. Stress, and how the body deals with it, is known to be a contributing factor in mood disorders. One of the main neural systems involved in stress is the hypothalamic-pituitary-adrenal (HPA) axis, a complex system that connects input from the brain to the synthesis and release of glucocorticoid hormones from the adrenal gland. Although glucocorticoids (e.g. cortisol) play an important short-term role in helping us respond to stress, prolonged activation of the HPA axis can detrimentally affect brain function and behaviour. Research indicates that sex steroids such as testosterone help shape stress-related pathways in the brain, and contribute to why some individuals are predisposed to stress-related mood disorders. Prior to birth, males normally experience a surge in testosterone that has been shown to have a profound and permanent influence on brain structure, behaviour, and HPA function during adulthood. However, where and how this occurs in the brain has not been determined. Brenda Bingham is determining the HPA-regulating regions in the brain that are altered by this early surge in testosterone. She will explore how early testosterone exposure determines the capacity of these brain regions to respond to changes in circulating testosterone levels during adulthood. She is focusing on the function of androgen receptors, which allow the brain to respond to testosterone, and on the neuropeptide vasopressin. Bingham’s research will provide insight into the HPA-regulating brain regions and circuits that are altered by testosterone exposure early in life. Ultimately, she hopes this work will lead to the development of novel therapeutic strategies aimed at tackling depressive disorders.