 This video will cover the second part of the following objective from the endocrine system, list the major endocrine organs and the hormones they secrete, then for each hormone discuss its effects on target cells. 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. Adrenal, referring to kidneys, or 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. The primary glucocorticoid is cortisol, and this is a long-term stress-response hormone that will function to increase blood glucose levels. Hence the name 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 an alarm phase of the stress response, which works to increase the heart rate, and also works to increase blood glucose levels, helps to 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 the 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. Cortisol will help produce a long-term resistance phase response to stress. One of the effects is that it increases blood glucose levels, 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 diseases and other disorders of excessive inflammation. 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. Here we can see the histology of the adrenal gland with the deep layer, the adrenal medulla, where there are large veins and arteries, large blood vessels inside of the adrenal medulla. Then the outer layer of the adrenal cortex contains the cells that produce the steroid hormones, including the major glucocorticoid hormone cortisol. And then surrounding the entire adrenal gland is a capsule. There's a capsule of connective tissue with a dense fibrous layer and then surrounding that fibrous layer is a loose layer containing adipose tissue. Here we see a higher magnification view of the adrenal gland. You can see a large blood vessel inside of the medulla of the adrenal gland and then surrounding the adrenal medulla, you can see the adrenal cortex. Here's another low magnification image of the adrenal gland. You can see numerous blood vessels in the adrenal medulla and then surrounding the adrenal medulla is the adrenal cortex. You can see the staining pattern of the adrenal cortex is lighter compared to the staining pattern in the adrenal medulla. This is a result of the cells in the adrenal cortex producing lipid hormones, the steroid hormones such as cortisol. Here's a higher magnification view focused on the layers of the adrenal cortex. The most superficial layer, zona glomerulosa, contains cells that produce aldosterone. The middle layer, the largest layer, zona fasciculata, contains the cells that produce cortisol. And then the deepest layer, zona reticularis, contains the cells that produce DHEA, the androgen hormone. 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. An abnormally elevated level of glucocorticoid signaling leads to Cushing's syndrome. This could be the result of a tumor that produces excess of 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. Cushing's syndrome results from excess cortisol signaling, excessive glucocorticoid receptor signaling and it will stimulate many of the normal effects that cortisol would have. Cortisol normally stimulates an increased appetite and so in Cushing's syndrome an increased appetite is one of the symptoms. Hyperglycemia, high blood glucose levels is a symptom of Cushing's 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's syndrome. Cortisol stimulates an increase in blood pressure. Weight gain is another symptom of Cushing's 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. In Cushing's syndrome this leads to deposition of fat, increased deposition of fat and there is abnormal localization of these depositions of fat including 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's 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's 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's syndrome is seen with Addison's disease where there is low cortisol. Cushing's disease results from an autoimmune attack of the adrenal cortex which destroys the cells in the zona fasciculata that produce cortisol. 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, weight loss, fatigue and weakness. So you get fatigue and weakness largely because of a decreased appetite, a low energy intake, also low energy available for cells because there is low blood glucose levels, low blood pressure. These are contributing to the fatigue and weakness because the cells are essentially starving for energy. Another symptom of Addison's disease is hyperpigmentation and this symptom can be seen in the pictures of patients with Addison's disease shown here. This hyperpigmentation results from abnormally high levels of ACTH, adrenal corticotropic hormone. ACTH has a chemical structure similar to another hormone, melanocyte stimulating hormone. 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 is 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 hyperpigmentation.