Hypothalamus and Pituitary Gland location relative to brain
- The pituitary gland, or hypophysis (from a Greek term meaning “to grow underneath”), lies in a pocket (called the sella turcica) of the sphenoid bone at the base of the brain (Figure 11.14) just below the hypothalamus.
- The pituitary gland is connected to the hypothalamus by the infundibulum, or pituitary stalk, containing axons from neurons in the hypothalamus and small blood vessels.
Anterior and posterior pituitary
- In humans, the pituitary gland is primarily composed of two adjacent lobes called the anterior lobe—usually referred to as the anterior pituitary gland or adenohypophysis—and the posterior lobe—usually called the posterior pituitary or neurohypophysis.
- The anterior pituitary gland arises embryologically from an invagination [the action or process of being turned inside out or folded back on itself to form a cavity or pouch] of the pharynx called Rathke’s pouch, whereas the posterior pituitary is not actually a gland but, rather, an extension of the neural components of the hypothalamus.
- The axons of two well-defined clusters of hypothalamic neurons (the supraoptic and paraventricular nuclei) pass down the infundibulum and end within the posterior pituitary in close proximity to capillaries (small blood vessels where exchange of solutes occurs between the blood and interstitium) (Figure 11.14b).
- Therefore, these neurons do not form a synapse with other neurons. Instead, their terminals end directly on capillaries. The terminals release hormones into these capillaries, which then drain into veins and the general circulation.
- In contrast to the neural connections between the hypothalamus and posterior pituitary, there are no important neural connections between the hypothalamus and anterior pituitary gland. There is, however, a special type of vascular connection.
- The junction of the hypothalamus and infundibulum is known as the median eminence.
- Capillaries in the median eminence recombine to form the hypothalamo–hypophyseal portal vessels (or portal veins).
- The term portal denotes veins that connect two sets of capillaries; normally, capillaries drain into veins that return blood to the heart. Only in portal systems does one set of capillaries drain into veins that then form a second set of capillaries before eventually emptying again into veins that return to the heart.
- The hypothalamo–hypophyseal portal vessels pass down the infundibulum and enter the anterior pituitary gland, where they drain into a second set of capillaries, the anterior pituitary gland capillaries.
- Thus, the hypothalamo–hypophyseal portal vessels offer a local route for blood to be delivered directly from the median eminence to the cells of the anterior pituitary gland.
- As we will see shortly, this local blood system provides a mechanism for hormones synthesized in cell bodies in the hypothalamus to directly alter the activity of the cells of the anterior pituitary gland, bypassing the general circulation and thus efficiently and specifically regulating hormone release from that gland.
Posterior pituitary hormone path
- We emphasized that the posterior pituitary is really a neural extension of the hypothalamus.
- The hormones are synthesized not in the posterior pituitary itself but in the hypothalamus—specifically in the cell bodies of the supraoptic and paraventricular nuclei, whose axons pass down the infundibulum and terminate in the posterior pituitary
- Enclosed in small vesicles, the hormone is transported down the axons to accumulate at the axon terminals in the posterior pituitary.
- Various stimuli activate inputs to these neurons, causing action potentials that propagate to the axon terminals and trigger the release of the stored hormone by exocytosis.
- The hormone then enters capillaries to be carried away by the blood returning to the heart.
- In this way, the brain can receive stimuli and respond as if it were an endocrine organ.
- By releasing its hormones into the general circulation, the posterior pituitary can modify the functions of distant organs.
Two posterior pituitary hormones- oxytocin
- The two posterior pituitary hormones are the peptides oxytocin and vasopressin.
- Oxytocin is involved in two reflexes related to reproduction.
- In one case, oxytocin stimulates contraction of smooth muscle cells in the breasts, which results in milk ejection during lactation.
- This occurs in response to stimulation of the nipples of the breast during nursing of the infant.
- Sensory cells within the nipples send stimulatory neural signals to the brain that terminate on the hypothalamic cells that make oxytocin, causing their activation and thus release of the hormone.
- In a second reflex, one that occurs during labor in a pregnant woman, stretch receptors in the cervix send neural signals back to the hypothalamus, which releases oxytocin in response.
- Oxytocin then stimulates contraction of uterine smooth muscle cells, until eventually the baby is born.
- Although oxytocin is also present in males, its systemic endocrine functions in males are uncertain.
- Recent research suggests that oxytocin may be involved in various aspects of memory and behavior in male and female mammals, possibly including humans. These include such things as pair bonding, maternal behavior, and emotions such as love.
- If true in humans, this is likely due to oxytocin-containing neurons in other parts of the brain, as it is unclear whether any systemic oxytocin can cross the blood–brain barrier and enter the brain.
Two posterior pituitary hormones- vasopressin
- The other posterior pituitary hormone, vasopressin, acts on smooth muscle cells around blood vessels to cause their contraction, which constricts the blood vessels and thereby increases blood pressure.
- This may occur, for example, in response to a decrease in blood pressure that resulted from a loss of blood due to an injury.
- Vasopressin also acts within the kidneys to decrease water excretion in the urine, thereby retaining fluid in the body and helping to maintain blood volume. One way in which this would occur would be if a person were to become dehydrated.
- Because of its kidney function, vasopressin is also known as antidiuretic hormone (ADH).
- (An increase in the volume of water excreted in the urine is known as a
- diuresis, and because vasopressin decreases water loss in the urine, it has antidiuretic properties.)
Anterior Pituitary Gland Hormones and the Hypothalamus
- Other nuclei of hypothalamic neurons secrete hormones that control the secretion of all the anterior pituitary gland hormones.
- For simplicity’s sake, Figure 11.14 depicts these neurons as arising from a single nucleus, but in fact several hypothalamic nuclei send axons whose terminals end in the median eminence.
- The hypothalamic hormones that regulate anterior pituitary gland function are collectively termed hypophysiotropic hormones (recall that another name for the pituitary gland is hypophysis); they are also commonly called hypothalamic releasing or inhibiting hormones.
- With one exception (dopamine), each of the hypophysiotropic hormones is the first in a three-hormone sequence:
- (1) A hypophysiotropic hormone controls the secretion of (2) an anterior pituitary gland hormone, which controls the secretion of (3) a hormone from some other endocrine gland. This last hormone then acts on its target cells.
- The adaptive value of such sequences is that they permit a variety of types of important hormonal feedback.
- They also allow amplification of a response of a small number of hypothalamic neurons into a large peripheral hormonal signal.
- We begin our description of these sequences in the middle—that is, with the anterior pituitary gland hormones— because the names of the hypophysiotropic hormones are mostly based on the names of the anterior pituitary gland hormones.
Overview of Anterior Pituitary Gland Hormones
- The anterior pituitary gland secretes at least six hormones that have well-established functions in humans.
- These six hormones—all peptides—are follicle-stimulating hormone (FSH), luteinizing hormone (LH), growth hormone (GH, also known as somatotropin), thyroid-stimulating hormone (TSH, also known as thyrotropin), prolactin, and adrenocorticotropic hormone (ACTH, also known as corticotropin).
- Each of the last four is secreted by a distinct cell type in the anterior pituitary gland, whereas FSH and LH, collectively termed gonadotropic hormones (or gonadotropins) because they stimulate the gonads, are often secreted by the same cells.
- Two other peptides—beta-lipotropin and beta-endorphin— are both derived from the same prohormone as ACTH, but their physiological roles in humans are unclear.
- In animal studies, however, beta-endorphin has been shown to have pain-killing effects, and beta-lipotropin can mobilize fats in the circulation to provide a source of energy. Both of these functions may contribute to the ability to cope with stressful challenges.
- Figure 11.16 summarizes the target organs and major functions of the six classical anterior pituitary gland hormones.
- Note that the only major function of two of the six is to stimulate their target cells to synthesize and secrete other hormones (and to maintain the growth and function of these cells).
- Thyroid-stimulating hormone induces the thyroid to secrete thyroxine and triiodothyronine. Adrenocorticotropic hormone stimulates the adrenal cortex to secrete cortisol.
- Three other anterior pituitary gland hormones also stimulate the secretion of another hormone but have additional functions as well.
- Growth hormone stimulates the liver to secrete a growth-promoting peptide hormone known as insulin-like growth factor 1 (IGF-1) and, in addition, exerts direct effects on bone and on metabolism.
- Follicle-stimulating hormone and luteinizing hormone stimulate the gonads to secrete the sex hormones—estradiol and progesterone from the ovaries, or testosterone from the testes; in addition, however, they regulate the growth and development of ova and sperm.
- Prolactin is unique among the six classical anterior pituitary gland hormones in that its major function is not to exert control over the secretion of a hormone by another endocrine gland.
- Its most important action is to stimulate development of the mammary glands during pregnancy and milk production when a woman is nursing (lactating); this occurs by direct effects upon gland cells in the breasts.
- During lactation, prolactin exerts a secondary action to inhibit gonadotropin secretion, thereby decreasing fertility when a woman is nursing.
- In the male, the physiological functions of prolactin are still under investigation
Hypophysiotropic Hormones path
- As stated previously, secretion of the anterior pituitary gland hormones is largely regulated by hormones produced by the hypothalamus and collectively called hypophysiotropic hormones.
- These hormones are secreted by neurons that originate in discrete nuclei of the hypothalamus and terminate in the median eminence around the capillaries that are the origins of the hypothalamo–hypophyseal portal vessels.
- The generation of action potentials in these neurons causes them to secrete their hormones by exocytosis, much as action potentials cause other neurons to release neurotransmitters by exocytosis.
- Hypothalamic hormones, however, enter the median eminence capillaries and are carried by the hypothalamo–hypophyseal portal vessels to the anterior pituitary gland.
- There, they diffuse out of the anterior pituitary gland capillaries into the interstitial fluid surrounding the various anterior pituitary gland cells.
- Upon binding to specific membrane-bound receptors, the hypothalamic hormones act to stimulate or inhibit the secretion of the different anterior pituitary gland hormones.
- These hypothalamic neurons secrete hormones in a manner identical to that described previously for the hypothalamic neurons whose axons end in the posterior pituitary.
- In both cases, the hormones are synthesized in cell bodies of the hypothalamic neurons, pass down axons to the neuron terminals, and are released in response to action potentials in the neurons.
- Two crucial differences, however, distinguish the two systems.
- First, the axons of the hypothalamic neurons that secrete the posterior pituitary hormones leave the hypothalamus and end in the posterior pituitary, whereas those that secrete the hypophysiotropic hormones remain in the hypothalamus, ending on capillaries in the median eminence.
- Second, most of the capillaries into which the posterior pituitary hormones are secreted immediately drain into the general circulation, which carries the hormones to the heart for distribution to the entire body.
- In contrast, the hypophysiotropic hormones enter capillaries in the median eminence of the hypothalamus that do not directly join the main bloodstream but empty into the hypothalamo– hypophyseal portal vessels, which carry them to the cells of the anterior pituitary gland.
- When an anterior pituitary gland hormone is secreted, it will diffuse into the same capillaries that delivered the hypophysiotropic hormone.
- These capillaries then drain into veins, which enter the general blood circulation, from which the anterior pituitary gland hormones come into contact with their target cells.
- The portal circulatory system ensures that hypophysiotropic hormones can reach the cells of the anterior pituitary gland with very little delay.
- The small total blood flow in the portal veins allows extremely small amounts of hypophysiotropic hormones from relatively few hypothalamic neurons to control the secretion of anterior pituitary hormones without dilution in the systemic circulation.
- This is an excellent illustration of the general principle of physiology that structure is a determinant of— and has coevolved with—function.
- By releasing hypophysiotropic factors into relatively few veins with a low total blood flow, the concentration of hypophysiotropic factors can increase rapidly leading to a larger increase in the release of anterior pituitary hormones (amplification).
- Also, the total amount of hypophysiotropic hormones entering the general circulation is very low, which prevents them from having unintended effects in the rest of the body.
Types of hypophysiotropic hormones
- There are multiple hypophysiotropic hormones, each influencing the release of one or, in at least one case, two of the anterior pituitary gland hormones.
- For simplicity Figure 11.18 and the text of this chapter summarize only those hypophysiotropic hormones that have clearly documented physiological roles in humans.
- Several of the hypophysiotropic hormones are named for the anterior pituitary gland hormone whose secretion they control.
- Thus, secretion of ACTH (corticotropin) is stimulated by corticotropinreleasing hormone (CRH), secretion of growth hormone is stimulated by growth hormone–releasing hormone (GHRH), secretion of thyroid-stimulating hormone (thyrotropin) is stimulated by thyrotropinreleasing hormone (TRH), and secretion of both luteinizing hormone and follicle-stimulating hormone (the gonadotropins) is stimulated by gonadotropin-releasing hormone (GnRH).However, note in Figure 11.18 that two of the hypophysiotropic hormones do not stimulate the release of an anterior pituitary gland hormone but, rather, inhibit its release.
- One of them, somatostatin (SST), inhibits the secretion of growth hormone.
- The other, dopamine (DA), inhibits the secretion of prolactin.
- As Figure 11.18 shows, growth hormone is controlled by two hypophysiotropic hormones—somatostatin, which inhibits its release, and growth hormone–releasing hormone, which stimulates it.
- The rate of growth hormone secretion depends, therefore, upon the relative amounts of the opposing hormones released by the hypothalamic neurons, as well as upon the relative sensitivities of the GH-producing cells of the anterior pituitary gland to them.
- This is a key example of the general principle of physiology that most physiological functions are controlled by multiple regulatory systems, often working in opposition.
- Such dual controls may also exist for the other anterior pituitary gland hormones.
- This is particularly true in the case of prolactin where the evidence for a prolactin-releasing hormone in laboratory animals is reasonably strong (the importance of such control for prolactin in humans, if it exists, is uncertain).
- Given that the hypophysiotropic hormones control anterior pituitary gland function, we must now ask: What controls secretion of the hypophysiotropic hormones themselves? Some of the neurons that secrete hypophysiotropic hormones may possess spontaneous activity, but the firing of most of them requires neural and hormonal input.
Neural Control of Hypophysiotropic Hormones
- Neurons of the hypothalamus receive stimulatory and inhibitory synaptic input from virtually all areas of the central nervous system, and specific neural pathways influence the secretion of the individual hypophysiotropic hormones.
- A large number of neurotransmitters, such as the catecholamines and serotonin, are released at synapses on the hypothalamic neurons that produce hypophysiotropic hormones.
- Not surprisingly, drugs that influence these neurotransmitters can alter the secretion of the hypophysiotropic hormones.
- In addition, there is a strong circadian influence over the secretion of certain hypophysiotropic hormones.
- The neural inputs to these cells arise from other regions of the hypothalamus, which in turn are linked to inputs from visual pathways that recognize the presence or absence of light.
- A good example of this type of neural control is that of CRH, the secretion
- of which is tied to the day/night cycle in mammals.
- This pattern results in ACTH and cortisol concentrations in the blood that begin to increase just prior to the waking period
Hormonal Feedback Control of the Hypothalamus and Anterior Pituitary Gland
- A prominent feature of each of the hormonal sequences initiated by a hypophysiotropic hormone is negative feedback exerted upon the hypothalamo–hypophyseal system by one or more of the hormones in its sequence.
- Negative feedback is a key component of most homeostatic control systems.
- In this case, it is effective in dampening hormonal responses—that is, in limiting the extremes of hormone secretory rates.
- For example, when a stressful stimulus elicits increased secretion, in turn, of CRH, ACTH, and cortisol, the resulting increase in plasma cortisol concentration feeds back to inhibit the CRH-secreting neurons of the hypothalamus and the ACTH-secreting cells of the anterior pituitary gland.
- Therefore, cortisol secretion does not increase as much as it would without negative feedback.
- Cortisol negative feedback is also critical in terminating the ACTH response to a stress. This is important because of the potentially damaging effects of excess cortisol on immune function and metabolic reactions, among others.
- The situation described for cortisol, in which the hormone secreted by the third endocrine gland in a sequence exerts a negative feedback effect over the anterior pituitary gland and/ or hypothalamus, is known as a long-loop negative feedback.
- Long-loop feedback does not exist for prolactin because this is one anterior pituitary gland hormone that does not have major control over another endocrine gland—that is, it does not participate in a three-hormone sequence.
- Nonetheless, there is negative feedback in the prolactin system, for this hormone itself acts upon the hypothalamus to stimulate the secretion of dopamine, which then inhibits the secretion of prolactin.
- The influence of an anterior pituitary gland hormone on the hypothalamus is known as a short-loop negative feedback.
- Like prolactin, several other anterior pituitary gland hormones, including growth hormone, also exert such feedback on the hypothalamus.
The Role of “Nonsequence” Hormones on the Hypothalamus and Anterior Pituitary Gland
- There are many stimulatory and inhibitory hormonal influences on the hypothalamus and/or anterior pituitary gland other than those that fit the feedback patterns just described.
- In other words, a hormone that is not itself in a particular hormonal sequence may nevertheless exert important influences on the secretion of the hypophysiotropic or anterior pituitary gland hormones in that sequence.
- For example, estradiol markedly enhances the secretion of prolactin by the
- anterior pituitary gland, even though estradiol secretion is not normally controlled by prolactin.
- Thus, the sequences we have been describing should not be viewed as isolated units.