Chapter 18: The Endocrine System
18–1 Intercellular Communication
In a few specialized cases, cellular activities are coordinated by the exchange of ions and molecules from one cell to the next across gap junctions. This direct communication occurs between two cells of the same type, and the cells must be in extensive physical contact. The two cells communicate so closely that they function as a single entity. For example, gap junctions (1) coordinate ciliary movement among epithelial cells, (2) coordinate the contractions of cardiac muscle cells, and (3) facilitate the propagation of action potentials from one neuron to the next at electrical synapses.
Direct communication is highly specialized and relatively rare. Most of the communication between cells involves the release and receipt of chemical messages. The use of chemical messengers to transfer information from cell to cell within a single tissue is called paracrine communication . The chemicals involved are called paracrine factors, also known as cytokines, or local hormones .
Some paracrine factors, including several of the prostaglandins and related chemicals, have primary effects in their tissues of origin and secondary effects in other tissues and organs. When secondary effects occur, the paracrine factors are also acting as hormones. Hormones are chemical messengers that are released in one tissue and transported in the bloodstream to reach specific cells in other tissues.
Each hormone has target cells , specific cells that respond to its presence. These cells possess the receptors needed to bind and "read" the hormonal message. The other hormones are treated like junk mail and ignored, because the cell lacks the receptors to read the messages they contain. The use of hormones to coordinate cellular activities in tissues in distant portions of the body is called endocrine communication .
A hormone may
stimulate the synthesis of an enzyme or a structural protein not already present in the cytoplasm by activating appropriate genes in the cell nucleus;
increase or decrease the rate of synthesis of a particular enzyme or other protein by changing the rate of transcription or translation; or
turn an existing enzyme "on" or "off" by changing its shape or structure.
The nervous system also relies primarily on chemical communication, but it does not use the bloodstream to deliver messages. Instead, neurons release a neurotransmitter at a synapse very close to the target cells that bear the appropriate receptors. This form of synaptic communication is ideal for crisis management: If you are in danger of being hit by a speeding bus, the nervous system can coordinate and direct your leap to safety. the differences between the nervous and endocrine systems seem relatively clear.
18–2 An Overview of the Endocrine
The endocrine system includes all the endocrine cells and tissues of the body which produce hormones or paracrine factors that have effects beyond their tissues of origin.
Hormones can be divided into three groups on the basis of their chemical structure: (1) amino acid derivatives , (2) peptide hormones , and (3) lipid derivatives .
Amino Acid Derivatives are relatively small molecules that are structurally related to amino acids, the building blocks of proteins. This group of hormones, sometimes known as the biogenic amines , includes epinephrine, norepinephrine, dopamine, the thyroid hormonboth E and NE are secreted by the adrenal medullae during sympathetic activation.
Hormones are chains
of amino acids. In general, peptide hormones are produced as
prohormones–inactive molecules that are converted to active hormones either
before or after they are secreted.
Peptide hormones can be divided into two groups. One large and diverse group includes hormones that range from short polypeptide chains, such as antidiuretic hormone (
group of peptide hormones consists of glycoproteins. These proteins are more
than 200 amino acids long and have carbohydrate side chains. The glycoproteins
There are two classes of lipid derivatives : (1) steroid hormones , derived from cholesterol, and (2) eicosanoids , derived from arachidonic acid , a 20–carbon fatty acid.
Steroid Hormones Steroid hormones are lipids structurally similar to cholesterol. Steroid hormones are released by male and female reproductive organs ( androgens by the testes, estrogens and progestins by the ovaries), the adrenal glands ( corticosteroids ), and the kidneys ( calcitriol ).
Eicosanoids are small molecules with a five–carbon ring at one end. These compounds are important paracrine factors that coordinate cellular activities and affect enzymatic processes (such as blood clotting) that occur in extracellular fluids. Some of the eicosanoids also have secondary roles as hormones. Examples of important eicosanoids include the following:
Distribution of Hormones
Hormone release typically occurs where capillaries are abundant, and the hormones quickly enter the bloodstream for distribution throughout the body. A freely circulating hormone remains functional for less than one hour, and sometimes for as little as two minutes. It is inactivated when (1) it diffuses out of the bloodstream and binds to receptors in target tissues, (2) it is absorbed and broken down by cells of the liver or kidneys, or (3) it is broken down by enzymes in the plasma or interstitial fluids.
Thyroid hormones and steroid hormones remain in circulation much longer, because when these hormones enter the bloodstream, almost all of them become attached to special transport proteins. Thus, the bloodstream contains a substantial reserve (several weeks' supply) of these hormones at any time.
Mechanisms of Hormone Action
Hormone receptors are located either (1) on the cell membrane or (2) inside the cell.
the Cell Membrane
The receptors for catecholamines (E, NE, and dopamine), peptide hormones, and eicosanoids are in the cell membranes of their respective target cells.
Because catecholamines and peptide hormones are not lipid soluble, they are unable to penetrate a cell membrane. Instead, these hormones bind to receptor proteins at the outer surface of the cell membrane. Eicosanoids, which are lipid soluble, diffuse across the membrane to reach receptor proteins on the inner surface of the membrane.
Steroid hormones diffuse across the lipid part of the cell membrane and bind to receptors in the cytoplasm or nucleus. The hormone–receptor complexes then activate or deactivate specific genes. By this mechanism, steroid hormones can alter the rate of
Control of Endocrine Activity
reflexes are the
functional counterparts of neural reflexes. They can be triggered by (1)
stimuli (changes in
the composition of the extracellular fluid), (2) hormonal
stimuli (the arrival
or removal of a specific hormone), or (3) neural
stimuli (the arrival
of neurotransmitter at neuroglandular junctions). In most cases, endocrine
reflexes are controlled by negative feedback mechanisms: A stimulus triggers the
production of a hormone whose direct or indirect effects reduce the intensity of
Endocrine cells in a simple endocrine reflex involve only one hormone. The endocrine cells involved respond directly to changes in the composition of the extracellular fluid. The secreted hormone adjusts the activities of target cells and restores homeostasis. Simple endocrine reflexes control hormone secretion by the heart, pancreas, parathyroid gland, and digestive tract.
More complex endocrine reflexes involve one or more intermediary steps and two or more hormones. The hypothalamus, the highest level of endocrine control, integrates the activities of the nervous and endocrine systems.
18–3 The Pituitary Gland hangs inferior to the hypothalamus, connected by the slender, funnel–shaped structure called the infundibulum. The base of the infundibulum lies between the optic chiasm and the mamillary bodies. The pituitary gland is cradled by the sella turcica and held in position by the diaphragma sellae , a dural sheet that encircles the infundibulum. The diaphragma sellae locks the pituitary gland in position and isolates it from the cranial cavity.
The pituitary gland can be divided into posterior and anterior lobes on the basis of function and developmental anatomy. Nine important peptide hormones are released by the pituitary gland–seven by the anterior lobe and two by the posterior lobe.
The Anterior Lobeof the pituitary gland, or adenohypophysis, contains a variety of endocrine cells. The anterior lobe can be subdivided into three regions: (1) the pars distalis, which is the largest and most anterior portion of the pituitary gland; (2) an extension called the pars tuberalis , which wraps around the adjacent portion of the infundibulum; and (3) the slender pars intermedia , which forms a narrow band bordering the posterior lobe
Control of the Anterior Lobe
Two classes of hypothalamic regulatory hormones exist: (1) releasing hormones and (2) inhibiting hormones. A releasing hormone ( RH ) stimulates the synthesis and secretion of one or more hormones at the anterior lobe, whereas an inhibiting hormone ( IH ) prevents the synthesis and secretion of hormones from the anterior lobe. An endocrine cell in the anterior lobe may be controlled by releasing hormones, inhibiting hormones, or some combination of the two. The regulatory hormones released at the hypothalamus are transported directly to the anterior lobe by the hypophyseal portal system.
Hormones of the Anterior Lobe
Adrenocorticotropic hormone Adrenocorticotropic hormone ( ACTH ), also known as corticotropin , stimulates the release of steroid hormones by the adrenal cortex , the outer portion of the adrenal gland. ACTH specifically targets cells that produce gluco–corticoids, hormones that affect glucose metabolism. ACTH release occurs under the stimulation of corticotropin–releasing hormone ( CRH ) from the hypothalamus. As glucocorticoid levels increase, the rates of CRH release and ACTH release decline.
The Gonadotropins Follicle–stimulating hormone and luteinizing hormone are called gonadotropins, because they regulate the activities of the gonads . (These organs–the testes and ovaries in males and females, respectively–produce reproductive cells as well as hormones.) The production of gonadotropins occurs under stimulation by gonadotropin–releasing hormone (GnRH) from the hypothalamus. An abnormally low production of gonadotropins produces hypogonadism . Children with this condition will not undergo sexual maturation, and adults with hypogonadism cannot produce functional sperm or oocytes.
Luteinizing hormone (
production of reproductive cells in females. It also promotes the secretion, by
the ovaries, of estrogens and the progestins
prepare the body for possible pregnancy. In males, this gonadotropin is
sometimes called interstitial
cell–stimulating hormone (ICSH) , because it
stimulates the production of sex hormones by the interstitial
cells of the
testes. These sex hormones are called androgens, the most
important of which is testosterone
Prolactin production is inhibited by prolactin–inhibiting hormone ( PIH )–the neurotransmitter dopamine. The hypothalamus also secretes a prolactin–releasing hormone, but the identity of this prolactin–releasing factor ( PRF ) is a mystery. Circulating
Growth hormone ( GH ), or somatotropin, stimulates cell growth and replication by accelerating the rate of protein synthesis.
The direct actions of GH are:
production of GH is regulated by growth
hormone– releasing hormone (
hormone–inhibiting hormone (
) from the
hypothalamus. Somatomedins stimulate GH–IH and inhibit GH–RH.
Hormone The pars
intermedia may secrete two forms of melanocyte–stimulating
hormone (MSH) , or
. As the name
indicates, MSH stimulates the melanocytes of the skin, increasing their
production of melanin, a brown, black, or yellow–brown pigment. The release of
MSH is inhibited by dopamine.
Melanocyte stimulating hormone is important in the control of skin pigmentation in fishes, amphibians, reptiles, and many mammals other than primates. The pars intermedia in adult humans is virtually nonfunctional, and the circulating blood usually does not contain MSH. However, MSH is secreted by the human pars intermedia (1) during fetal development, (2) in very young children, (3) in pregnant women, and (4) in some diseases. The functional significance of MSH secretion under these circumstances is not known. The administration of a synthetic form of MSH causes the skin to darken, so MSH has been suggested as a means of obtaining a "sunless tan."
Growth Hormone Abnormalities
Growth hormone stimulates muscular and skeletal development. If it is administered before the epiphyseal cartilages have closed, it will cause an increase in height, weight, and muscle mass. In extreme cases, gigantism can result. In acromegaly, an excessive amount of GH is released after puberty, when most of the epiphyseal cartilages have already closed. Cartilages and small bones respond to the hormone, however, resulting in abnormal growth of the hands, feet, lower jaw, skull, and clavicle.
Acromegaly results from the overproduction of growth hormone after the epiphyseal cartilages have closed. Bone shapes change, and cartilaginous areas of the skeleton enlarge. Notice the broad facial features and the enlarged lower jaw.
Children who are unable to produce adequate concentrations of GH have pituitary growth failure. The steady growth and maturation that typically precede and accompany puberty do not occur in these individuals, who have short stature, slow epiphyseal growth, and larger–than–normal adipose tissue reserves.
growth patterns can be restored by the administration of GH. Before the advent
of gene splicing and recombinant
The current availability of purified human growth hormone has led to its use under medically questionable circumstances. For example, it is now being praised as an "antiaging" miracle cure. Although GH supplements do slow or even reverse the losses in bone and muscle mass that accompany aging, little is known about adverse side effects that may accompany long–term use of the hormone in mature adults.
GH is also being sought by some parents of short but otherwise healthy children. These parents view short stature as a handicap that merits treatment by a physician. Whether we are considering GH treatment of adults or children, it is important to remember that GH and the somatomedins affect many different tissues and have widespread metabolic impacts. For example, children exposed to GH may grow faster, but their body fat content declines drastically and sexual maturation is delayed. The decline is associated with metabolic changes in many organs. The range and significance of these metabolic side effects are now the subject of long–term studies.
pituitary gland is also called the neurohypophysis, or
part), because it contains the axons of hypothalamic neurons. Neurons of the
antidiuretic hormone (
Antidiuretic hormone (
Diabetes occurs in several forms, all
characterized by excessive urine production (polyuria). Although diabetes can be
caused by physical damage to the kidneys, most forms are the result of endocrine
abnormalities. The two most prevalent forms are diabetes mellitus and diabetes
insipidus. Diabetes mellitus is described on page 633. Diabetes
insipidus generally develops because the posterior lobe of the
pituitary gland no longer releases adequate amounts of
Mild cases of diabetes insipidus may not require treatment if fluid and electrolyte intake keep pace with urinary losses. In severe cases, the fluid losses can reach 10 liters per day, and dehydration and electrolyte imbalances are fatal without treatment
In women, oxytocin, or OT , stimulates smooth muscle tissue in the wall of the uterus, promoting labor and delivery. After delivery, oxytocin stimulates the contraction of myoepithelial cells around the secretory alveoli and the ducts of the mammary glands, promoting the ejection of milk.
last stages of pregnancy, the uterine smooth muscles are relatively insensitive
to oxytocin, but sensitivity becomes more pronounced as the time of delivery
approaches. The trigger for normal labor and delivery is probably a sudden rise
in oxytocin levels at the uterus. There is good evidence, however, that the
oxytocin released at the posterior lobe plays only a supporting role and that
most of the oxytocin involved is secreted by the uterus and fetus.
secretion and milk ejection are part of a neuroendocrine reflex. The stimulus is
an infant suckling at the breast, and sensory nerves innervating the nipples
relay the information to the hypothalamus. Oxytocin is then released into the
circulation at the posterior lobe, and the myoepithelial cells respond by
squeezing milk from the secretory alveoli into large collecting ducts. This
let–down reflex can be
modified by any factor that affects the hypothalamus. For example, anxiety,
stress, and other factors can prevent the flow of milk, even when the mammary
glands are fully functional. In contrast, nursing mothers can become conditioned
to associate a baby's crying with suckling. These women may begin milk let–down
as soon as they hear a baby cry.
Although the functions of oxytocin in sexual activity remain uncertain, it is known that circulating concentrations of oxytocin in both genders rise during sexual arousal and peak at orgasm. Evidence indicates that in men oxytocin stimulates smooth muscle contractions in the walls of the sperm duct ( ductus deferens ) and prostate gland. These actions may be important in emission –the ejection of secretions of the prostate gland, sperm, and the secretions of other glands into the male reproductive tract before ejaculation. Studies suggest that the oxytocin released during intercourse in females may stimulate smooth muscle contractions in the uterus and vagina that promote the transport of sperm toward the uterine tubes.
Summary: The Hormones of the Pituitary Gland
18–4 The Thyroid Gland curves across the anterior surface of the trachea just inferior to the thyroid cartilage , which forms most of the anterior surface of the larynx
The two lobes of the thyroid gland are united by a slender connection, the isthmus.
Thyroid Follicles and Thyroid Hormones
The thyroid gland contains large numbers of thyroid follicles , spheres lined by a simple cuboidal epithelium. Follicle cells synthesize a globular protein called thyroglobulin and secrete it into the colloid of the thyroid follicles. Each thyroglobulin molecule contains the amino acid tyrosine , the building block of thyroid hormones.
The formation of thyroid hormones involves three basic steps:
factor controlling the rate of thyroid hormone release is the concentration of
Thyroid hormones readily cross cell membranes, and they affect almost every cell in the body. Inside a cell, they bind to (1) receptors in the cytoplasm, (2) receptors on the surfaces of mitochondria, and (3) receptors in the nucleus.
hormones also activate genes that code for the synthesis of enzymes involved in
glycolysis and ATP production. This effect, coupled with the direct effect of
thyroid hormones on mitochondria, increases the metabolic rate of the cell.
Because the cell consumes more energy and because energy use is measured in
, the effect
is called the calorigenic
effect of thyroid
hormones. When the metabolic rate increases, more heat is generated. In young
T3 Versus T4
The thyroid gland produces large amounts of T4 but T3 is primarily responsible for the observed effects of thyroid hormones: a strong, immediate, and short–lived increase in the rate of cellular metabolism. Peripheral tissues have two sources of T3
Iodine in the diet is absorbed at the digestive tract. The thyroid follicles contain most of the iodide reserves in the body. The typical diet in the
The C Cells
of the Thyroid Gland: Calcitonin
A second population of endocrine cells lies sandwiched between the cuboidal follicle cells and their basement membrane. These cells, which are larger than those of the follicular epithelium and do not stain as clearly, are the C ( clear ) cells , or parafollicular cells. C cells produce the hormone calcitonin ( CT ), which aids in the regulation of concentrations in body fluids. We introduced the functions of this hormone in Chapter 6 . The net effect of calcitonin release is a drop in the concentration in body fluids, accomplished by (1) the inhibition of osteoclasts, which slows the rate of release from bone, and (2) the stimulation and then falloff of excretion at the kidneys.
Calcitonin is probably most important during childhood, when it stimulates bone growth and mineral deposition in the skeleton. It also appears to be important in reducing the loss of bone mass (1) during prolonged starvation and (2) in the late stages of pregnancy, when the maternal skeleton competes with the developing fetus for calcium ions absorbed by the digestive tract.
Thyroid Gland Disorders
production of thyroid hormones establishes the background rates of cellular
metabolism. These hormones exert their primary effects on metabolically active
tissues and organs, including skeletal muscles, the liver, and the kidneys. The
inadequate production of thyroid hormones is called hypothy–roidism
. In an infant, hypothyroidism produces cretinism
, a condition marked by inadequate skeletal and nervous
development and a metabolic rate as much as 40 percent below normal levels. The
condition affects approximately 1 birth out of every 5000. Cretinism developing
later in childhood will retard growth and mental development and delay puberty.
Adults with hypothyroidism are lethargic and unable to tolerate cold
temperatures. The symptoms of adult hypothyroidism, collectively known as myxedema, include
subcutaneous swelling, dry skin, hair loss, low body temperature, muscular
weakness, and slowed reflexes. Hypothyroidism may also be associated with the
enlargement of the thyroid gland, producing a distinctive swelling called a
goiter. Hypothyroidism, myxedema, and goiter as the result of inadequate dietary
iodide are very rare in the
(a) Cretinism, or congenital hypothyroidism, results from thyroid hormone insufficiency in infancy. (b) An enlarged thyroid gland, or goiter, can be associated with thyroid hyposecretion due to iodine insufficiency in adults.
Hyperthyroidism , or thyrotoxicosis , occurs when thyroid hormones are produced in excessive quantities. The metabolic rate climbs, and the skin becomes flushed and moist with perspiration. Blood pressure and heart rate increase, and the heartbeat may become irregular as circulatory demands escalate. The effects on the central nervous system make the individual restless, excitable, and subject to shifts in mood and emotional states. Despite the drive for increased activity, the person has limited energy reserves and fatigues easily. Graves' disease is a form of hyperthyroidism that afflicted President George W. H. Bush and Barbara Bush during their stay in the White House.
18–5 The Parathyroid Glands
There are normally two pairs of parathyroid glands embedded in the posterior surfaces of the thyroid gland
parathyroid glands have at least two cell populations: The chief
parathyroid hormone; the functions of the other cells, called
Like the C cells of the thyroid gland, the chief cells monitor the circulating concentration of calcium ions. When the concentration of the blood falls below normal, the chief cells secrete parathyroid hormone( PTH ), or parathormone . The net result of PTH secretion is an increase in concentration in body fluids. Parathyroid hormone has four major effects:
When the parathyroid gland secretes inadequate or excessive amounts of parathyroid hormone, concentrations move outside normal homeostatic limits. Inadequate parathyroid hormone production, a condition called hypoparathyroidism , leads to low concentrations in body fluids. The most obvious symptoms involve neural and muscle tissues: The nervous system becomes more excitable, and the affected individual may experience hypocalcemic tetany , a dangerous condition characterized by prolonged muscle spasms that initially involve the limbs and face.
In hyperparathyroidism , concentrations become abnormally high. Bones grow thin and brittle, skeletal muscles become weak, CNS function is depressed, and nausea and vomiting occur. In severe cases, the patient may become comatose.