The adrenal cortex and the adrenal medulla play major roles in response to stress. In general, stress activates nervous and endocrine responses that prepare the body for physical activity, even when physical activity is not the most appropriate response to the stressful conditions, such as during an examination or other mentally stressful situations. The endocrine response to stress involves increased CRH release from the hypothalamus and increased sympathetic stimulation of the adrenal medulla. CRH stimulates ACTH secretion from the anterior pituitary, which in turn stimulates cortisol from the adrenal medulla. Increased sympathetic stimulation of the adrenal medulla increases epinephrine and norepinephrine secretion.

Together epinephrine and cortisol increase blood glucose levels and the release of fatty acids from adipose tissue and the liver. Sympathetic innervation of the pancreas decreases insulin secretion. Consequently, most tissues do not readily take up and use glucose. Thus glucose is available primarily to the nervous system; and fatty acids are used by skeletal muscle, cardiac muscle, and other tissues.

Epinephrine and sympathetic stimulation also increase cardiac output, increase blood pressure, and act on the central nervous system to increase alertness and aggressiveness. Cortisol also decreases the initial inflammatory response.

Responses to stress illustrate the close relationship of the nervous and endocrine systems and provide an example of their integrated functions. Our ability to respond to stressful conditions depends on the nervous and endocrine responses to stress.

Although responses to stress are adaptive under many circumstances, they can become harmful. For example, if stress is chronic, the elevated secretion of cortisol and epinephrine produces harmful effects.