Although many endocrine organs receive signals from the hypothalamic–pituitary axis, some respond instead to internal physiological states of the body or to external environmental cues. One of these is the parathyroid gland, which is located on the thyroid gland. The parathyroid gland secretes parathyroid hormone (PTH). Working together with calcitonin, secreted by the thyroid gland, PTH controls the levels of calcium in the blood (Table 38.2). The two hormones act by regulating the actions of bone cells (osteoblasts and osteoclasts; Chapter 37) that control bone formation and bone removal.

When circulating levels of calcium fall too low, the parathyroid gland releases PTH, which stimulates osteoclasts to reabsorb bone mineral, halting bone formation and releasing calcium into the bloodstream. When calcium levels are too high, the production of PTH is inhibited and calcitonin is released to shift bone metabolism toward net bone formation, building bone that stores calcium in the skeleton. Note that, as with blood-glucose levels, calcium levels are maintained in a narrow range by negative feedback: The response to the hormone (increasing or decreasing levels of calcium in the blood) is the opposite of the stimulus (low or high levels of calcium in the blood) so that a stable set point is maintained.

Several organs of the digestive system, including the pancreas, stomach, and duodenum, produce hormones that regulate appetite and digestion. Three of these hormones are discussed in Chapter 40.

The pineal gland is located in the thalamic region of the brain. In response to darkness, the pineal gland secretes melatonin, a hormone that helps control an animal’s state of wakefulness (Table 38.2). Melatonin secretion is inhibited when environmental light cues sensed by the retina are conveyed to the gland by the autonomic nervous system. In other vertebrates, such as lampreys, some fishes, and reptiles, the pineal gland responds to light sensed by a “third eye,” photosensitive cells located at the skull’s surface between the animal’s actual eyes. In both cases, melatonin levels rise at night. In diurnal animals (those that are active during the day), the rise in melatonin levels at night causes the animals to sleep. In nocturnal animals (those that are active during the night), the rise in melatonin levels causes them to become active. The release of melatonin in response to daily (and seasonal) light cycles helps to maintain circadian rhythms of the body. Circadian rhythms are cycles of about 24 hours in which an animal’s biochemical, physiological, and behavioral state shifts in response to changes in daily and seasonal environmental conditions. To overcome jet lag, travelers are advised to seek sunlight and often to take melatonin before sleeping to help reset their 24-hour circadian rhythm.

In several animals, including ground squirrels, bats, bears, and rattlesnakes, the pineal gland regulates hibernation, controlling the animal’s metabolic state over longer time periods. In many animals, release of melatonin also regulates seasonal breeding cycles.