Critical influence of neonatal testosterone on stress pathways in the adult brain

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A frontline of defense against threats to homeostasis (i.e. stress) is provided by the hypothalamic- pituitary-adrenal (HPA) axis, which governs the mobilization of energy stores under challenging situations. Sex differences in the activity of the HPA axis can be explained, in part, by the inhibitory actions of testosterone in males and by the stimulatory actions of estrogen in females. However, manipulating androgen and estrogen exposure over the perinatal period in the rat causes profound and permanent (organizing) effects on HPA responsiveness to stress during adulthood. Several studies continue to show an involvement of androgen and estrogen receptors in mediating the organizational effects of sex steroids on HPA outflow. However, our research has shown that the principle regulator of the HPA axis, the paraventricular nucleus of the hypothalamus, is devoid of sex steroid receptors within neurons that regulate HPA outflow directly. Thus, how and where the organizing effects of sex steroids are executed in the brain has not been resolved.