Inferior and slightly anterior to the thalamus is the hypothalamus, the other major region of the diencephalon. The hypothalamus is a collection of nuclei that are largely involved in regulating homeostasis. The hypothalamus is the executive region in charge of the autonomic nervous system and the endocrine system through its regulation of the anterior pituitary gland. Other parts of the hypothalamus are involved in memory and emotion as part of the limbic system.

The hypothalamus, about the size of a pearl, directs a multitude of important functions. It wakes you up in the morning, and gets the adrenaline flowing during a test or job interview. The hypothalamus is also an important emotional center, controlling the molecules that make you feel exhilarated, angry, or unhappy. Near the hypothalamus lies the thalamus, a major clearinghouse for information going to and from the spinal cord and the cerebrum.

Diencephalon

The diencephalons is centrally located and is nearly surrounded by the cerebral hemispheres. It includes the thalamus, hypothalamus, and epithalamus. The thalamus, about 80 percent of the diencephalons, consists of two oval masses of gray matter that serve as relay stations for sensory impulses, except for the sense of smell, going to the cerebral cortex. The hypothalamus is a small region below the thalamus, which plays a key role in maintaining homeostasis because it regulates many visceral activities. The epithalamus is the most dorsal portion of the diencephalons. This small gland is involved with the onset of puberty and rhythmic cycles in the body. It is like a biological clock.

The pupillary light reflex (Figure) begins when light hits the retina and causes a signal to travel along the optic nerve. This is visual sensation, because the afferent branch of this reflex is simply sharing the special sense pathway. Bright light hitting the retina leads to the parasympathetic response, through the oculomotor nerve, followed by the postganglionic fiber from the ciliary ganglion, which stimulates the circular fibers of the iris to contract and constrict the pupil. When light hits the retina in one eye, both pupils contract. When that light is removed, both pupils dilate again back to the resting position. When the stimulus is unilateral (presented to only one eye), the response is bilateral (both eyes). The same is not true for somatic reflexes. If you touch a hot radiator, you only pull that arm back, not both. Central control of autonomic reflexes is different than for somatic reflexes. The hypothalamus, along with other CNS locations, controls the autonomic system.

Forebrain Structures

Autonomic control is based on the visceral reflexes, composed of the afferent and efferent branches. These homeostatic mechanisms are based on the balance between the two divisions of the autonomic system, which results in tone for various organs that is based on the predominant input from the sympathetic or parasympathetic systems. Coordinating that balance requires integration that begins with forebrain structures like the hypothalamus and continues into the brain stem and spinal cord.

The Hypothalamus

The hypothalamus is the control center for many homeostatic mechanisms. It regulates both autonomic function and endocrine function. The roles it plays in the pupillary reflexes demonstrates the importance of this control center. The optic nerve projects primarily to the thalamus, which is the necessary relay to the occipital cortex for conscious visual perception. Another projection of the optic nerve, however, goes to the hypothalamus.

The hypothalamus then uses this visual system input to drive the pupillary reflexes. If the retina is activated by high levels of light, the hypothalamus stimulates the parasympathetic response. If the optic nerve message shows that low levels of light are falling on the retina, the hypothalamus activates the sympathetic response. Output from the hypothalamus follows two main tracts, the dorsal longitudinal fasciculus and the medial forebrain bundle (image). Along these two tracts, the hypothalamus can influence the Eddinger–Westphal nucleus of the oculomotor complex or the lateral horns of the thoracic spinal cord.

These two tracts connect the hypothalamus with the major parasympathetic nuclei in the brain stem and the preganglionic (central) neurons of the thoracolumbar spinal cord. The hypothalamus also receives input from other areas of the forebrain through the medial forebrain bundle. The olfactory cortex, the septal nuclei of the basal forebrain, and the amygdala project into the hypothalamus through the medial forebrain bundle. These forebrain structures inform the hypothalamus about the state of the nervous system and can influence the regulatory processes of homeostasis. A good example of this is found in the amygdala, which is found beneath the cerebral cortex of the temporal lobe and plays a role in our ability to remember and feel emotions.

The Amygdala

The amygdala is a group of nuclei in the medial region of the temporal lobe that is part of the limbic lobe (image). The limbic lobe includes structures that are involved in emotional responses, as well as structures that contribute to memory function. The limbic lobe has strong connections with the hypothalamus and influences the state of its activity on the basis of emotional state. For example, when you are anxious or scared, the amygdala will send signals to the hypothalamus along the medial forebrain bundle that will stimulate the sympathetic fight-or-flight response. The hypothalamus will also stimulate the release of stress hormones through its control of the endocrine system in response to amygdala input.

The hypothalamus in vertebrates integrates the endocrine and nervous systems. The hypothalamus is an endocrine organ located in the diencephalon of the brain. It receives input from the body and other brain areas and initiates endocrine responses to environmental changes. The hypothalamus acts as an endocrine organ, synthesizing hormones and transporting them along axons to the posterior pituitary gland. It synthesizes and secretes regulatory hormones that control the endocrine cells in the anterior pituitary gland. The hypothalamus contains autonomic centers that control endocrine cells in the adrenal medulla via neuronal control.

The pituitary gland, sometimes called the hypophysis or “master gland” is located at the base of the brain in the sella turcica, a groove of the sphenoid bone of the skull, illustrated in Figure 37.15. It is attached to the hypothalamus via a stalk called the pituitary stalk (or infundibulum). The anterior portion of the pituitary gland is regulated by releasing or release-inhibiting hormones produced by the hypothalamus, and the posterior pituitary receives signals via neurosecretory cells to release hormones produced by the hypothalamus. The pituitary has two distinct regions—the anterior pituitary and the posterior pituitary—which between them secrete nine different peptide or protein hormones. The posterior lobe of the pituitary gland contains axons of the hypothalamic neurons.

Figure 37.15 The pituitary gland is located at (a) the base of the brain and (b) connected to the hypothalamus by the pituitary stalk. (credit a: modification of work by NCI; credit b: modification of work by Gray’s Anatomy)

Anterior Pituitary

The anterior pituitary gland, or adenohypophysis, is surrounded by a capillary network that extends from the hypothalamus, down along the infundibulum, and to the anterior pituitary. This capillary network is a part of the hypophyseal portal system that carries substances from the hypothalamus to the anterior pituitary and hormones from the anterior pituitary into the circulatory system. A portal system carries blood from one capillary network to another; therefore, the hypophyseal portal system allows hormones produced by the hypothalamus to be carried directly to the anterior pituitary without first entering the circulatory system.

The anterior pituitary produces seven hormones: growth hormone (GH), prolactin (PRL), thyroid-stimulating hormone (TSH), melanin-stimulating hormone (MSH), adrenocorticotropic hormone (ACTH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). Anterior pituitary hormones are sometimes referred to as tropic hormones, because they control the functioning of other organs. While these hormones are produced by the anterior pituitary, their production is controlled by regulatory hormones produced by the hypothalamus. These regulatory hormones can be releasing hormones or inhibiting hormones, causing more or less of the anterior pituitary hormones to be secreted. These travel from the hypothalamus through the hypophyseal portal system to the anterior pituitary where they exert their effect. Negative feedback then regulates how much of these regulatory hormones are released and how much anterior pituitary hormone is secreted.

Posterior Pituitary

The posterior pituitary is significantly different in structure from the anterior pituitary. It is a part of the brain, extending down from the hypothalamus, and contains mostly nerve fibers and neuroglial cells, which support axons that extend from the hypothalamus to the posterior pituitary. The posterior pituitary and the infundibulum together are referred to as the neurohypophysis.

The hormones antidiuretic hormone (ADH), also known as vasopressin, and oxytocin are produced by neurons in the hypothalamus and transported within these axons along the infundibulum to the posterior pituitary. They are released into the circulatory system via neural signaling from the hypothalamus. These hormones are considered to be posterior pituitary hormones, even though they are produced by the hypothalamus, because that is where they are released into the circulatory system. The posterior pituitary itself does not produce hormones, but instead stores hormones produced by the hypothalamus and releases them into the bloodstream.

The anterior pituitary originates from the digestive tract in the embryo and migrates toward the brain during fetal development. There are three regions: the pars distalis is the most anterior, the pars intermedia is adjacent to the posterior pituitary, and the pars tuberalis is a slender “tube” that wraps the infundibulum.

Recall that the posterior pituitary does not synthesize hormones, but merely stores them. In contrast, the anterior pituitary does manufacture hormones. However, the secretion of hormones from the anterior pituitary is regulated by two classes of hormones. These hormones—secreted by the hypothalamus—are the releasing hormones that stimulate the secretion of hormones from the anterior pituitary and the inhibiting hormones that inhibit secretion.

Hypothalamic hormones are secreted by neurons, but enter the anterior pituitary through blood vessels (image). Within the infundibulum is a bridge of capillaries that connects the hypothalamus to the anterior pituitary. This network, called the hypophyseal portal system, allows hypothalamic hormones to be transported to the anterior pituitary without first entering the systemic circulation. The system originates from the superior hypophyseal artery, which branches off the carotid arteries and transports blood to the hypothalamus. The branches of the superior hypophyseal artery form the hypophyseal portal system (see image). Hypothalamic releasing and inhibiting hormones travel through a primary capillary plexus to the portal veins, which carry them into the anterior pituitary. Hormones produced by the anterior pituitary (in response to releasing hormones) enter a secondary capillary plexus, and from there drain into the circulation.

The anterior pituitary produces seven hormones. These are the growth hormone (GH), thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), beta endorphin, and prolactin. Of the hormones of the anterior pituitary, TSH, ACTH, FSH, and LH are collectively referred to as tropic hormones (trope- = “turning”) because they turn on or off the function of other endocrine glands.

Growth Hormone

The endocrine system regulates the growth of the human body, protein synthesis, and cellular replication. A major hormone involved in this process is growth hormone (GH), also called somatotropin—a protein hormone produced and secreted by the anterior pituitary gland. Its primary function is anabolic; it promotes protein synthesis and tissue building through direct and indirect mechanisms (image). GH levels are controlled by the release of GHRH and GHIH (also known as somatostatin) from the hypothalamus.

A glucose-sparing effect occurs when GH stimulates lipolysis, or the breakdown of adipose tissue, releasing fatty acids into the blood. As a result, many tissues switch from glucose to fatty acids as their main energy source, which means that less glucose is taken up from the bloodstream.

GH also initiates the diabetogenic effect in which GH stimulates the liver to break down glycogen to glucose, which is then deposited into the blood. The name “diabetogenic” is derived from the similarity in elevated blood glucose levels observed between individuals with untreated diabetes mellitus and individuals experiencing GH excess. Blood glucose levels rise as the result of a combination of glucose-sparing and diabetogenic effects.

GH indirectly mediates growth and protein synthesis by triggering the liver and other tissues to produce a group of proteins called insulin-like growth factors (IGFs). These proteins enhance cellular proliferation and inhibit apoptosis, or programmed cell death. IGFs stimulate cells to increase their uptake of amino acids from the blood for protein synthesis. Skeletal muscle and cartilage cells are particularly sensitive to stimulation from IGFs.

Dysfunction of the endocrine system’s control of growth can result in several disorders. For example, gigantism is a disorder in children that is caused by the secretion of abnormally large amounts of GH, resulting in excessive growth. A similar condition in adults is acromegaly, a disorder that results in the growth of bones in the face, hands, and feet in response to excessive levels of GH in individuals who have stopped growing. Abnormally low levels of GH in children can cause growth impairment—a disorder called pituitary dwarfism (also known as growth hormone deficiency).

Thyroid-Stimulating Hormone

The activity of the thyroid gland is regulated by thyroid-stimulating hormone (TSH), also called thyrotropin. TSH is released from the anterior pituitary in response to thyrotropin-releasing hormone (TRH) from the hypothalamus. As discussed shortly, it triggers the secretion of thyroid hormones by the thyroid gland. In a classic negative feedback loop, elevated levels of thyroid hormones in the bloodstream then trigger a drop in production of TRH and subsequently TSH.

Adrenocorticotropic Hormone

The adrenocorticotropic hormone (ACTH), also called corticotropin, stimulates the adrenal cortex (the more superficial “bark” of the adrenal glands) to secrete corticosteroid hormones such as cortisol. ACTH come from a precursor molecule known as pro-opiomelanotropin (POMC) which produces several biologically active molecules when cleaved, including ACTH, melanocyte-stimulating hormone, and the brain opioid peptides known as endorphins.

The release of ACTH is regulated by the corticotropin-releasing hormone (CRH) from the hypothalamus in response to normal physiologic rhythms. A variety of stressors can also influence its release, and the role of ACTH in the stress response is discussed later in this chapter.

Follicle-Stimulating Hormone and Luteinizing Hormone

The endocrine glands secrete a variety of hormones that control the development and regulation of the reproductive system (these glands include the anterior pituitary, the adrenal cortex, and the gonads—the testes in males and the ovaries in females). Much of the development of the reproductive system occurs during puberty and is marked by the development of sex-specific characteristics in both male and female adolescents. Puberty is initiated by gonadotropin-releasing hormone (GnRH), a hormone produced and secreted by the hypothalamus. GnRH stimulates the anterior pituitary to secrete gonadotropins—hormones that regulate the function of the gonads. The levels of GnRH are regulated through a negative feedback loop; high levels of reproductive hormones inhibit the release of GnRH. Throughout life, gonadotropins regulate reproductive function and, in the case of women, the onset and cessation of reproductive capacity.

The gonadotropins include two glycoprotein hormones: follicle-stimulating hormone (FSH) stimulates the production and maturation of sex cells, or gametes, including ova in women and sperm in men. FSH also promotes follicular growth; these follicles then release estrogens in the female ovaries. Luteinizing hormone (LH) triggers ovulation in women, as well as the production of estrogens and progesterone by the ovaries. LH stimulates production of testosterone by the male testes.

Prolactin

As its name implies, prolactin (PRL) promotes lactation (milk production) in women. During pregnancy, it contributes to development of the mammary glands, and after birth, it stimulates the mammary glands to produce breast milk. However, the effects of prolactin depend heavily upon the permissive effects of estrogens, progesterone, and other hormones. And as noted earlier, the let-down of milk occurs in response to stimulation from oxytocin.

In a non-pregnant woman, prolactin secretion is inhibited by prolactin-inhibiting hormone (PIH), which is actually the neurotransmitter dopamine, and is released from neurons in the hypothalamus. Only during pregnancy do prolactin levels rise in response to prolactin-releasing hormone (PRH) from the hypothalamus.