 In this video I will describe the structure and function of the adrenal glands, discuss the effects of the adrenal hormones epinephrine, norepinephrine, aldosterone, and cortisol, and compare Cushing's syndrome and Addison's disease. In previous videos we have discussed the role of the hypothalamus, pituitary gland, thyroid gland, and parathyroid glands. This video will focus on the adrenal glands, which are a pair of pyramid shaped organs located superior to the kidneys. The adrenal glands are also known as the suprarenal glands, indicating their location superior to the kidneys, renal referring to kidneys, so suprarenal or adrenal glands are these pyramid shaped glands located superior to the kidneys. The adrenal glands produce stress response hormones. The adrenal glands are organized into two distinct regions that produce different hormones. The outer layer is the cortex and the adrenal cortex produces the steroid glucocorticoid hormone cortisol, whereas deep within the adrenal gland a region known as the adrenal medulla produces epinephrine, also known as adrenaline. Epinephrine is released in response to the sympathetic nervous system and this is rapidly released in an alarm phase response to stress. In contrast cortisol, the steroid hormone produced from the adrenal cortex is released in response to a hormone. The tropic hormone from the anterior pituitary known as ACTH or adrenal corticotropic hormone stimulates the adrenal cortex to release the glucocorticoid steroid hormone cortisol. Both of these stress response hormones will stimulate an increase in blood glucose levels as one of their ways of helping the body cope with stress. In the hypothalamic pituitary adrenal axis or HPA axis the hypothalamus responds to stress by releasing CRH the corticotropin releasing hormone into the hypothysyl portal circuit the blood flowing into the anterior pituitary. CRH then binds to receptors on the surface of cells in the anterior pituitary and stimulates the release of ACTH adrenal corticotropic hormone. ACTH then travels in the blood to the adrenal cortex and binds to receptors on the surface of cells in the adrenal cortex where it stimulates the production of glucocorticoids and the primary glucocorticoid is cortisol. This is a long-term stress response hormone that will function to increase blood glucose levels hence the name glucocorticoid. Glucocorticoid is produced by the adrenal cortex and stimulates an increased blood glucose level and a synonym for glucocorticoid is cortisol. On the top left we can see the chemical structure of cortisol the major glucocorticoid in humans which is a steroid hormone produced from cholesterol. On the top right we can see the chemical structure of epinephrine also known as adrenaline which is the major catecholamine hormone produced by the adrenal medulla in response to sympathetic nervous system activity. Norepinephrine is also produced by the adrenal medulla in response to the sympathetic nervous system and these are both the catecholamine hormones. Epinephrine and norepinephrine are produced rapidly in response to sympathetic nervous system activity as a alarm phase of the stress response which works to increase the heart rate and also works to increase blood glucose levels helps mobilize energy reserves in order to help cells in the body respond to stress. Cortisol is produced in response to a hormonal stimulus in response to ACTH adrenal corticotropic hormone from the anterior pituitary ACTH binds to receptors on the surface of cells in the zona fasciculata the middle layer of three layers in the adrenal cortex and these cells in zona fasciculata then synthesize cortisol and cortisol then travels throughout the blood binding to receptors called glucocorticoid receptors which are in cells all throughout the body and cortisol will help produce a long-term resistance phase response to stress one of the effects is that it increases blood glucose levels and hence the name glucocorticoid cortisol is produced in the cortex and increases glucose levels so glucocorticoid cortisol increases blood glucose levels cortisol also has the effect of increasing appetite and it will also have an anti-inflammatory effect which is important because we can take advantage of this medically using medications that bind to the glucocorticoid receptor we can inhibit the immune system in autoimmune system diseases and other disorders of excessive inflammation so there are three layers of the adrenal cortex we can see the superficial layer is zona glomerulosa which produces the mineral corticoid hormone aldosterone another steroid hormone aldosterone binds to receptors within cells in the kidney and will stimulate the reabsorption of sodium as a mechanism contributing to increase blood volume and blood pressure then the deepest layer of the adrenal cortex is called zona reticularis which contains cells that produce androgen hormones including dehydroepidendosterone abbreviated DHEA which can stimulate masculinization effects by binding to the same receptor as testosterone the androgen receptor in women DHEA has an important role during puberty DHEA will stimulate maturation of the hair follicles during puberty a negative feedback homeostatic control mechanism regulates the production of the glucocorticoid cortisol from the adrenal cortex cortisol binds to glucocorticoid receptors within cells in the hypothalamus and inhibits the release of CRH the corticotropin releasing hormone this leads to a decreased production of ACTH leading to decreased production of glucocorticoids helping to maintain a stable homeostatic concentration of glucocorticoids in response to stress the hypothalamus will increase the production of CRH and that will produce more ACTH leading to more glucocorticoid release helping to respond to stress but the homeostatic set point will then be returned back to the baseline once the stressor has been removed and abnormally elevated level of glucocorticoid signaling leads to cushing syndrome and this could be the result of a tumor that produces excessive ACTH levels leading to excess cortisol produced in the adrenal gland or it could be excessive use of anti-inflammatory medications that are similar to cortisol and also stimulate the same glucocorticoid receptor an example of a medication like this would be prednisone these are commonly prescribed in order to inhibit the inflammation that is contributing to autoimmune diseases and so cushing syndrome results from excess cortisol or excess cortisol signaling excessive glucocorticoid receptor signaling and it will stimulate many of the normal effects that cortisol would have so cortisol normally stimulates an increased appetite and so in cushing syndrome an increased appetite is one of the symptoms hyperglycemia high blood glucose levels is a symptom of cushing syndrome because one of the major effects of cortisol is to stimulate gluconeogenesis the production of glucose hypertension high blood pressure is another symptom of cushing syndrome cortisol stimulates an increase in blood pressure weight gain is another symptom of cushing syndrome in part as a result from increased appetite but also because of the way that cortisol affects your metabolism cortisol will stimulate fat metabolism and if you have an increased appetite this will stimulate increased fat production and in cushing syndrome this leads to deposition of fat increased deposition of fat and there's abnormal local abnormal localization of these depositions of fat including a facial distribution as well as a region on the back often causes a hump of adipose tissue to accumulate on the back fatigue and weakness are symptoms of cushing syndrome in part because cortisol will stimulate the breakdown of protein protein catabolism as a mechanism to fuel gluconeogenesis to produce more glucose and excessive hair production as we can see in the image on the left as well as stria stria are the red mark stretch marks that we can see on the skin these are other symptoms of cushing syndrome as well as the moon face the characteristic deposition of fat giving a rounded appearance to the face that we can see in the picture in the top right the opposite of cushing syndrome is seen with addison's disease where there's low cortisol so cushing's disease results from an autoimmune attack of the adrenal cortex which destroys the cells in the zonophysiculata that produce cortisol and so this causes an abnormally low cortisol level which leads to a decrease in the appetite hypoglycemia that is low blood glucose levels hypotension low blood pressure that is weight loss fatigue and weakness so you get fatigue and weakness largely because of a decreased appetite a low energy intake there's also low energy available for cells because there's low blood glucose levels there's low blood pressure and these are contributing to the fatigue and weakness because the cells are essentially starving for energy and another symptom of addison's disease is hyper pigmentation and this symptom can be seen in the pictures of patients with addison's disease shown here this hyper pigmentation results from abnormally high levels of acth adrenal corticotropic hormone acth has a chemical structure similar to another hormone melanocyte stimulating hormone and melanocyte stimulating hormone has the normal effect of stimulating melanocyte activity leading to the production of melanin the pigment that gives the skin color however in addison's disease because the negative feedback that maintains the homeostatic level of cortisol is disrupted excessive acth is produced and there's there's no cortisol to provide a negative feedback and acth has a structure similar enough that it can still bind to the melanocyte stimulating hormone receptor and therefore it stimulates the production of melanin leading to hyper pigmentation