The body's stress response is mediated by the interplay between the sympathetic nervous system (SNS) and the hypothalmic-pituitary-adrenal (HPA) axis. A complex interaction of direct influences and indirect feedback mechanisms among the SNS, the hypothalmus, the pituitary gland and the adrenal glands contributes to the neuroendocrine regulation involved in reactions to stress.

Mechanism of stress and stress response

The hypothalmic-pituitary-adrenal (HPA) axis is an endocrine cascade that mediates several aspects of physiological stress, including responses to acute stressors (i.e., fight-or-flight response) but it also causes chronic stress. 

This is a diagram of the mechanism of stress and stress response in the HPA axis. The hypothalamus secretes corticotropin releasing hormone and the anterior pituitary responds by releasing adrenocortictotropic hormone, that causes the adrenal cortex to activate a physical response.

Sympathetic Component

The SNS plays a key role in mediating the neural response to stress known as the fight-or-flight response. This response is also referred to as the sympatho-adrenal response of the body owing to the fact that the preganglionic sympathetic fibers that end in the adrenal medulla secrete acetylcholine, which activates the release of adrenaline and noradrenaline from the medulla. 

This response acts primarily on the cardiovascular system and is mediated directly via impulses transmitted through the sympathetic nervous system and indirectly via catecholamines, such as the adrenaline secreted from the adrenal medulla.

HPA Axis Component

A feedback loop exists among the components of the HPA axis and the SNS. The paraventricular nucleus of the hypothalmus contains neuroendocrine neurons that synthesize and release vasopressin—a hormone that acts in the HPA axis as a vasoconstrictor—and corticotropin releasing hormone (CRH). 

These two hormones regulate the anterior lobe of the pituitary gland and stimulate the release of adrenocorticotropic hormone (ACTH), also known as corticotropin. ACTH acts on the adrenal cortices that produce glucocorticoid hormones, like cortisol, which is a stress hormone that exerts many effects throughout the body. In the brain cortisol acts on both mineral corticoid and glucocorticoid receptors that are expressed by many different types of neurons.

CRH and vasopressin are released from nerve terminals. CRH gets transported to the anterior pituitary through the circulatory system and vasopressin is transported by axonal transport to the anterior pituitary. There, CRH and vasopressin act to stimulate the secretion of ACTH from the cells where it is synthesized. ACTH is then transported through the circulatory system to the adrenal cortex where it promotes the biosynthesis of corticosteroids like cortisol and cholesterol.

Glucocorticoids of the HPA axis have many important functions, including the modulation of stress reactions, but in excess they may be damaging. Researchers have hypothesized that the hormonal changes brought on by stress may contribute to the neural atrophies seen in many neurodegenerative disease states.