Hormones control many important functions. They are released from major endocrine glands, as well as from endocrine cells scattered throughout the body. Three types of stimuli cause hormone release: humoral stimuli, neural stimuli, and hormonal stimuli. For a humoral stimulus, hormone release is caused by altered levels of certain critical ions or nutrients in body fluids. This is called a humoral stimulus, because the fluids of the body, including blood, were once called "humors". You may have heard the word humors used in this way before— for example, the aqueous and vitreous humors of the eye. Hormones that regulate substances that are critically and immediately important for survival are often released in response to humoral stimuli. Knowing this, can you predict which of these substances might act as a humoral stimulus for hormone release? Is it (a) potassium ions; (b) glucose; (c) calcium ions; or (d) all of the above? The correct answer is (d), all of the above. Potassium and calcium are critically important for excitability of nerves and muscles, and glucose is essential as an energy source for the brain. For all humoral stimuli, the substance that the hormone regulates acts directly on the cells that release that hormone. Let's take calcium as an example. Blood levels of calcium are controlled by parathyroid hormone. Parathyroid hormone (or PTH) is released by parathyroid glands located on the posterior surface of the thyroid gland. When calcium levels in the blood fall, the cells of the parathyroid glands detect this decrease and release PTH. As you'll see later in the chapter. PTH acts in various ways to increase calcium levels in the blood. The restoration of normal calcium levels ends stimulation of the parathyroid cells, and so the release of PTH also ends. You may recognize this as a negative feedback loop. Remember that negative feedback mechanisms return a variable to its homeostatic value. The second type of stimulus, neural stimulus, is rare. In this case, hormone release is triggered by the firing of neurons. The best example of this is the control of the release of the hormones epinephrine and norepinephrine from the medullae of the adrenal glands. The release of these hormones is controlled by the nervous system. Let's see how this works. Various stressors, for example speaking to an audience, activate neurons in the hypothalamus. These neurons send action potentials down their axons to the spinal cord. There, they activate preganglionic sympathetic neurons whose axons form synapses with chromaffin cells of the adrenal medulla. It's these cells that release epinephrine and some norepinephrine. The hormones released by the adrenal medulla reinforce other sympathetic nervous system responses that help us deal with the stress. Unlike the other two types of stimuli for hormone release, neural stimuli have no negative feedback loop. Instead, release of the hormone ends when the neural stimulus ends, in this case, when your speech is over. The final type of stimulus is the most common among the major endocrine glands. You will see it over and over again in this book: hormonal stimulus. In this case, release of one hormone controls the release of another hormone. The anterior lobe of the pituitary gland releases six different hormones and each of them uses this pattern. In this case, releasing or inhibiting hormones are first secreted by the hypothalamus. They travel through special blood vessels to the anterior pituitary, where they stimulate or inhibit the release of anterior pituitary hormones. Two of the six hormones released by the anterior pituitary act directly on their target cells, but the other four go on to act on other endocrine glands: the thyroid gland, the adrenal cortex, and the gonads (either the ovaries in females or the testes in males). As you'll see later in the chapter, two different anterior pituitary hormones act on the gonads. These four anterior pituitary hormones maintain the activity of their target glands and stimulate them to release their own hormones. Hormones that stimulate the release of other hormones are called <i>tropic</i> hormones. Let's simplify this drawing as a flowchart. The hypothalamus secretes releasing or inhibiting hormones. We'll use a releasing hormone here. The releasing hormone acts on specific cells in the anterior pituitary. These cells, in turn, release a stimulating hormone that acts on another endocrine gland, the target gland. This causes the target gland to release its particular hormone that acts on its specific target cells in the body. This flowchart is useful in two ways. First, it helps you remember the pattern of release for the anterior pituitary tropic hormones. Second, it can show you where opportunities for negative feedback arise. For example, the same hormone that acts on target cells can also act on the hypothalamus and anterior pituitary, but in this case, it acts to turn <i>off</i> the releasing hormone and the tropic hormone using negative feedback. Let's take thyroid hormone as an example. In this case, the hypothalamus secretes thyrotropin-<i>releasing</i> hormone (or TRH). This causes the anterior pituitary to release thyroid-<i>stimulating</i> hormone (or TSH). This in turn causes the thyroid gland to release thyroid hormones that act on target cells throughout the body. In addition, thyroid hormones feed back on the hypothalamus and the anterior pituitary to decrease the release of TRH and TSH. You can apply these feedback loops to understand the results of certain lab tests of endocrine function. For example, suppose you have a patient who you think is not making enough thyroid hormones. You order a test to measure the level of thyroid-stimulating hormone in their blood. What do you think would happen to TSH levels in the blood if the body did not produce enough thyroid hormones? Is the correct answer (a) TSH levels would increase; (b) TSH levels would decrease; or (c) TSH levels would stay the same? The correct answer is (a), TSH levels would increase. This makes sense, because less thyroid hormone means less negative feedback on the anterior pituitary and hypothalamus. As a result, TSH levels will rise. For the same reason, TRH levels will also rise. You have now learned about the three types of stimuli that cause hormone release: humoral,... neural,… and hormonal. You will see more instances of each of these throughout the rest of this chapter. For each hormone you encounter, pay attention to what the stimulus is for release of that hormone. The type of stimulus for release will also tell you how release of that hormone is turned off.