The hypothalamus is a small, yet vitally important, brain region that integrates the body's two communication systems: the endocrine and nervous systems. It links the two by sending and receiving signals from other regions of the nervous system while also controlling the body's "master gland"—the pituitary gland. The pituitary, in turn, controls most other endocrine organs of the body.
The interaction between the hypothalamus, pituitary, and other endocrine glands is known as the hypothalamic–pituitary–endocrine axis. This animation shows how negative feedback loops keep hormone levels in check in this system. It also shows the relationship between the hypothalamus and the two very different halves of the pituitary.
Let's look at a negative feedback loop using the hormones of the adrenal cortex as an example. In response to stress signals, the hypothalamus releases corticotropin-releasing hormone, or CRH. CRH triggers the anterior pituitary to release adrenocorticotropic hormone, or ACTH. ACTH, in turn, triggers the adrenal cortex to release a steroid hormone called cortisol.
Cortisol has many effects on different target organs in the body, but the primary one is to increase glucose in the blood. This sugar is an energy resource that allows the body to respond to physiological or psychological stress.
In addition to acting on organs and tissues throughout the body, the hormones travel through the bloodstream back to the brain, where they inhibit the release of CRH.
Without CRH, the anterior pituitary does not release ACTH. In addition to this effect, the cortisol also acts directly on the anterior pituitary to inhibit ACTH release. Without ACTH, the adrenal cortex stops releasing cortisol.
This interaction is an example of a negative feedback loop. In this loop, the output of the system—the hormones from the adrenal cortex—ultimately diminish the input from the system—the hormones from the hypothalamus and anterior pituitary. This system turns on cortisol release, but then turns it off before cortisol levels get too high, keeping them at a fairly steady level.
Because cortisol is the final hormone released in this chain of interacting structures, called the hypothalamic–pituitary–adrenal axis, its feedback actions are called long-loop negative feedback. In this system, the tropic hormone ACTH also exerts negative feedback control on the hypothalamus, inhibiting CRH release. This action is called short-loop negative feedback because of the proximity of the pituitary and the hypothalamus.
The pituitary gland consists of two distinct parts with different developmental origins. The anterior pituitary originates as an outpocketing of the roof of the embryonic mouth cavity. The posterior pituitary originates as an outpocketing of the floor of the developing brain. Both parts interact with the nervous system but in different ways.
First consider the posterior pituitary. The posterior pituitary contains axons from neurons in the hypothalamus. These hypothalamic neurons produce two hormones: antidiuretic hormone (ADH) and oxytocin. Vesicles, loaded with ADH or oxytocin, are made in a cell body of a neuron and then transported to its axon terminal in the posterior pituitary.
The axon terminals abut tiny capillaries. If a neuron is stimulated and fires an action potential, the neuron releases its hormones from the axon terminals. The hormones quickly enter the capillaries and flow with the blood into the general circulation of the body.
The ADH-producing neurons respond to signals relating to thirst and water regulation. ADH stimulates the kidneys to conserve water, resulting in small volumes of highly concentrated urine. ADH also constricts peripheral blood vessels, which increases blood pressure. For this reason, ADH is also known as vasopressin.
The oxytocin-producing neurons respond to stimulation from a suckling baby. When these neurons fire action potentials, they release oxytocin into the general circulation. Oxytocin reaches the mammary glands, triggering them to express milk. These neurons are also activated during childbirth, during which oxytocin triggers uterine contractions.
Unlike the posterior pituitary, the anterior pituitary consists of glandular tissue. The gland consists of numerous cell types, which specialize in making and releasing specific hormones.
An elaborate web of capillaries, called the hypothalamic–pituitary portal blood vessels, connects the glandular cells with neurons from the hypothalamus. The neurons abut the capillaries, and when stimulated, release hormones into the portal circulation.
The hypothalamic hormones travel directly to the cells of the anterior pituitary. Here, a specific hormone affects a specific type of anterior pituitary cell. Each cell type, in turn, produces and releases its own hormones into the general circulation. Once released, the anterior pituitary hormones travel throughout the body to their various targets.
Here are some of the hypothalamic neurohormones. Let's look at the first one. Depending on the signals it receives, the hypothalamus may release thyrotropin releasing hormone or thyrotropin release-inhibiting hormone. If it releases the former, it stimulates the anterior pituitary to release thyrotropin. If the hypothalamus releases the latter, it inhibits the release of thyrotropin. Thyrotropin then triggers the thyroid gland to produce thyroid hormone. This table presents a subset of the hormones released by the hypothalamus and anterior pituitary.
Through its release of hormones, the hypothalamus controls reproduction, growth, metabolism, water conservation, blood pressure, lactation, childbirth, and responses to stress. Through its connections with other regions of the nervous system, the hypothalamus controls many other bodily functions.
The hypothalamus receives information about the state of the body and sends instructions—either through synaptic communication with other neurons or through the release of hormones—to keep the body's internal environment within a narrow operating range.
The negative feedback loops that operate in the hypothalamus–pituitary–endocrine axis provide some insight into how the hypothalamus maintains the body's internal environment. There are many examples of such feedback loops. For instance, the hypothalamus controls metabolic rate in part through the control of the thyroid gland. The hypothalamus releases thyrotropin-releasing hormone (TRH), which triggers the anterior pituitary to release thyrotropin, which in turn stimulates the thyroid gland to release thyroid hormones. The thyroid hormones travel throughout the body to stimulate cellular metabolism. In addition to their action throughout the body, the thyroid hormones also act on the hypothalamus, inhibiting it from releasing additional TRH. When the thyroid hormones drop to low levels—during which metabolism slows—the hypothalamus is released from inhibition and begins to release TRH again. The metabolic rate of the body thereby remains within a narrow range.