49.1. Hormones Affect Cellular Metabolism (p. 874)
A. Hormones
1. A hormone is an organic chemical produced by one set of cells that affects a different set.
2. A hormone travels through the circulatory system to its target organ.
3. A hormone does not seek out a particular organ; the organ awaits the arrival of the hormone.
4. Cells respond to a hormone depending on their receptors; they combine in a lock-and-key manner.
5. The endocrine system and the nervous system use chemicals messangers (hormones and neurotransmitters, respectively).
B. Steroid Hormones Activate DNA (Fig. 49.1) [transp. 277]
1. Some vertebrate hormones produced by the adrenal cortex, ovaries, and testes are steroids.
2. Steroid hormones are derived from cholesterol and stored in fat droplets in cell cytoplasm until their release.
3. They do not bind to cell surface receptors but enter the cell and nucleus freely.
4. Inside the nucleus, hormones such as estrogen and progesterone bind to a specific receptor.
5. Hormone-receptor complex binds to transcription factors that bind to DNA resulting in the activation of genes.
C. Nonsteroid Hormones Activate Enzymes (Fig. 49.2) [transp. 278]
1. Many vertebrate hormones are proteins or peptides coded for by genes and synthesized in cytoplasm at ribosomes.
2. Catecholamine hormones derived from the amino acid tyrosine require only a series of cytoplasm reactions.
3. Earl Sutherland, Jr. worked on epinephrine on liver cells; he hypothesized that this hormone binds to a cell-surface receptor resulting in a complex that leads to activation of an enzyme that produces cyclic AMP.
4. Cyclic AMP (cAMP) is made from ATP but has only one phosphate group attached to adenosine at two locations.
5. Nonsteroid hormones never enter a cell so they are the first messenger; cAMP that sets metabolic machinery in motion is the second messenger.
6. An intermediary between the first messenger and adenylate cyclase enzyme converts ATP to cAMP.
7. The hormone-receptor complex activates a G protein in the plasma membrane. (Fig. 49.2) [transp. 279]
a. G proteins are located in the membrane.
b. G proteins regulate the action of many other membrane proteins, particularly ion channels and enzymes.
c. They may be stimulatory or inhibitory; in this case they activate adenylate cyclase and cAMP results.
8. cAMP is a second messenger that sets an enzyme cascade in motion.
9. Activated enzymes can be used repeatedly, resulting in a thousand-fold response.
10. Peptide hormones act quickly but for a short period of time; cAMP is soon converted to an inactive product.
11. Other second messengers include inositol triphosphate (IP3) that causes release of calcium ions in muscle cells.
12. Hormones are involved in a signal transduction pathway; G proteins are involved in transducing the signal.
49.2. Human Endocrine System (p. 877) (Fig. 49.3) [transp. 280]
A. Endocrine Glands
1. The endocrine system consists of endocrine glands that coordinate body activities through hormones.
2. Endocrine glands are ductless glands in contrast to exocrine glands with ducts.
3. They produce hormones that are secreted into bloodstream and circulate until they bind to receptors of target cells.
4. A hormone may have a different function in different species.
a. The hormone prolactin stimulates breasts to secrete milk, but stimulates the gut in pigeons.
b. Thyroxine in human stimulates metabolism, but induces metamorphosis of tadpoles to frogs.
5. Some hormones are species specific; they function only in one species.
6. Principal human endocrine glands include hypothalamus, pineal, and pituitary glands located in the brain; thyroid and parathyroid glands located in the neck; ovaries located in the abdomen and testes in the scrotum; and thymus located in the thorax.
7. The endocrine system is especially involved with homeostasis (as is the nervous system).
8. The effect of hormones is controlled by negative feedback and contrary hormone action.
a. An endocrine gland can be sensitive to the condition it is monitoring or to the level of hormone produced.
b. Negative feedback control is one mechanism.
1) The pancreas produces insulin when blood glucose rises; this causes the liver to store glucose.
2) When glucose is stored, the level goes down and the pancreas stops insulin production.
c. Contrary actions of hormones can control hormonal regulation.
1) The effect of insulin is offset by the production of glucagon by the pancreas.
2) The thyroid lowers blood calcium level but the parathyroids raise the blood calcium level.
B. Hypothalamus Controls the Pituitary Gland
1. The hypothalamus is the portion of the brain that regulates the internal environment.
2. It controls heart beat, temperature, and water balance, as well as the glandular secretions of the pituitary gland.
3. The pituitary gland is about 1 cm in diameter and lies just below the hypothalamus and is comprised of two portions: the posterior pituitary and the anterior pituitary. (Fig. 49.5) [transp. 281]
4. Posterior Pituitary Stores Two Hormones
a. This portion of the pituitary gland is connected to the hypothalamus by means of a stalklike structure.
b. It contains portions of neurosecretory cells that originate in hypothalamus and respond to neurotransmitters and produce hormones.
c. The hypothalamus produces antidiuretic hormone (ADH or vasopressin) and oxytocin, which are stored in axon endings located in the posterior pituitary, until they are released.
d. Antidiuretic hormone (ADH) promotes reabsorption of water from collecting ducts in kidneys.
1) This nonsteroid hormone acts on collecting ducts by increasing their permeability to H2O, thereby increasing H2O retention and reducing urine output. (Table 49.1)
2) Nerve cells in the hypothalamus determine when blood is too concentrated; ADH is released and kidneys respond by reabsorbing water.
3) As blood becomes dilute, ADH is no longer released; this is a case of negative feedback.
e. Oxytocin is also made in the hypothalamus and stored in the posterior pituitary.
1) Oxytocin stimulates uterine muscle contraction and is used to artificially induce labor.
2) It also stimulates the release of milk from the mammary glands. (Table 49.1)
5. Anterior Pituitary Is the Master Gland (Fig. 49.5) [transp. 280]
a. In the 1930s, researchers knew stimulation of hypothalamus controlled release of anterior pituitary hormones; direct stimulation of pituitary did not.
b. R. Guillemin processed 2 million sheep hypothalami and A. V. Schally processed over a million pig hypothalami; both announced in November 1969 the isolation of a hypothalmic-releasing hormone, a peptide containing only 3 amino acids.
c. The hypothalamus produces hypothalamic-releasing and hypothalamic-release-inhibiting hormones, which pass to the anterior pituitary by way of a portal system.
1) Hypothalamus-releasing hormones produced in and released from the hypothalamus act on cells in the anterior pituitary to stimulate production and secretion of a specific hormone.
2) Hypothalamus-release-inhibiting hormones produced in and released from the hypothalamus act on cells in the anterior pituitary to inhibit the production and secretion of a specific hormone.
d. Anterior pituitary produces six different hormones, each by a distinct cell type. (Table 49.1)
e. Three of these hormones have direct effects on the body. (Table 44.1)
f. Growth hormone (GH or somatotropic hormone) promotes cell division, protein synthesis, and bone growth.
1) GH dramatically affects appearance and height of an individual.
2) Too little GH during childhood makes an individual a pituitary dwarf; too much forms a pituitary giant.
3) Overproduction of GH as an adult results in acromegaly; only the feet, hands, and face can respond.
4) GH acts to stimulate transport of amino acids into cells and to increase activity of ribosomes.
5) GH promotes growth of cartilaginous plates and osteoblasts to form bone; these effects may be indirect and due to somatomedins released by the liver in response to GH.
g. Prolactin (PRL) is produced in quantity only after childbirth.
1) Prolactin causes mammary glands in breast to produce milk by promoting cell division and protein synthesis.
2) It also plays a role in carbohydrate and fat metabolism.
h. Melanocyte-stimulating hormone (MSH) in humans stimulates melanocytes to increase synthesis of melanin.
1) MSH causes skin color changes in fishes, amphibians, and reptiles with melanophores, special skin cells.
2) MH is derived from a molecule that is a precursor for adrenocorticotropic hormone (ACTH) and anterior pituitary endorphins.
i. The anterior pituitary is sometimes called the master gland because it controls the secretion of some other endocrine glands.
j. Anterior pituitary secretes the following hormones:
1) Thyroid-stimulating hormone (TSH) which stimulates the thyroid to produce and secrete thyroxin.
2) Adrenocorticotropic hormone (ACTH) which stimulates the adrenal cortex to release cortisol.
3) Gonadotropic hormones (follicle-stimulating hormone [FSH] and luteinizing hormone [LH]) which act on the gonads (ovaries and testes) to secrete sex hormones.
k. A three-tiered relationship exists among hypothalamus, anterior pituitary, and other endocrine glands.
1) The hypothalamus produces releasing hormones, which control the anterior pituitary.
2) The anterior pituitary releases hormones that control the thyroid, the adrenal cortex, and the gonads.
3) In turn, these glands produce hormones that, through negative feedback mechanisms, regulate the secretion of appropriate hypothalamic-releasing hormone. (Fig. 49.6) [transp. 282]
C. Thyroid Gland Speeds Metabolism
1. Thyroid gland is located in neck and attached to trachea just below larynx. (Fig. 49.7a) [transp. 283]
2. The two hormones produced by the thyroid both contain iodine.
a. Thyroxine (T4) contains four iodine atoms; secreted in larger amounts than triiodothyronine but is less potent.
b. Triiodothyronine (T3) contains three iodine atoms; secreted in lesser amounts than T4, but is more potent.
3. Iodine is actively transported into the thyroid and may reach concentrations 25 times greater than in the blood.
4. Thyroid's need for iodine was known before biochemistry because lack of iodine causes enlargement (goiter).
a. The anterior pituitary produces TSH that stimulates the thyroid to secrete thyroxine.
b. Increased levels of thyroxine exert feedback control over anterior pituitary, which ceases TSH production.
c. With low thyroxin in blood, anterior pituitary continues to produce TSH; thyroid responds by increasing in size.
d. An increase in size (goiter) is ineffective since the thyroxine level is low due to iodine shortage.
e. Goiter is prevented by supplementing iodine in salt.
5. Thyroxine is necessary in vertebrates for proper development; without it, tadpoles do not metamorphose into frogs; humans do not mature properly.
6. Cretinism occurs in individuals who have suffered from low thyroid function since birth; they demonstrate reduced skeletal growth, sexual immaturity, and abnormal protein metabolism leading to mental retardation.
7. The thyroid gland also produces calcitonin.
a. Calcitonin lowers the level of calcium (Ca2+) in the blood.
b. It opposes the action of parathyroid hormone (PTH).
D. Parathyroid Glands Regulate Calcium
1. Four parathyroid glands are embedded in posterior surface of thyroid gland. (Fig. 49.7b) [transp. 283]
2. The parathyroid glands produce parathyroid hormone (PTH).
3. Under the influence of PTH, calcium level in the blood increases and the phosphate level decreases.
4. PTH stimulates the absorption of Ca2+ by activating vitamin D, the retention of Ca2+ (and excretion of phosphate) by the kidneys, and demineralization of bone by promoting the activity of osteoclasts.
5. When the blood calcium level reaches the right level, the parathyroid glands no longer produce PTH.
6. If PTH is not produced in response to low blood Ca2+, tetany results because Ca2+ plays an important role in both nerve conduction and muscle contraction.
7. In tetany, the body shakes from continuous muscle contraction due to increased excitability of the nerves that fire spontaneously and without rest.
E. Adrenal Glands Contain Two Parts
1. Each of the two adrenal glands lies atop a kidney.
2. Each gland consist of two parts: an outer cortex and an inner medulla. (Fig. 49.8)
3. Adrenal hormones increase during times of physical and emotional stress.
4. The hypothalamus exerts control over both portions.
a. Nerve impulses travel via brain stem and spinal cord to sympathetic nerve fibers to medulla to trigger hormones.
b. The hypothalamus also controls anterior pituitary's secretion of ACTH by secreting ACTH-releasing hormone.
F. Adrenal Medulla Responds to Stress
1. Epinephrine and norepinephrine are produced by the adrenal medulla.
2. Postganglionic fibers of the sympathetic system, which controls adrenal medulla, also secrete norepinephrine.
3. Both hormones bring about body changes corresponding to an emergency.
a. Blood glucose level rises and metabolic rate increases.
b. Bronchioles dilate and breathing rate increases.
c. Blood vessels to digestive tract and skin constrict; those to skeletal muscles dilate.
d. Cardiac muscle contracts more forcefully and heart rate increases.
G. Adrenal Cortex Also Responds to Stress
1. The adrenal cortex secretes two classes of hormones: glucocorticoids and mineralocorticoids.
a. Glucocorticoids help regulate blood glucose levels.
b. Mineralocorticoids regulate levels of minerals in the blood.
c. It also secretes a small amount of both male and female sex hormones in both sexes.
2. Cortisol is a glucocorticoid responsible for the most activity.
a. Cortisol promotes hydrolysis of muscle protein to amino acids that enter blood and travel to liver where they are converted to glucose.
b. Cortisol favors breakdown of fatty acids rather than carbohydrates; in opposition to insulin, cortisol raises blood glucose levels.
c. Cortisol counteracts the inflammatory response; it helps medicate arthritis and bursitis.
3. Aldosterone is the most important of the mineralocorticoids.
a. The primary target organ is the kidney where it promotes the reabsorption of Na+ and the excretion of K+.
b. Secretion of mineralocorticoids is controlled through the renin-angiotensin-aldosterone system. (Fig. 49.9)
1) Under low blood volume and sodium levels, the kidneys secrete renin.
2) The enzyme renin converts the plasma protein angiotensinogen to angiotensin I; this becomes angiotensin II by a converting enzyme in the lungs.
3) Angiotensin II stimulates the adrenal cortex to release aldosterone.
4) Angiotensin I constricts arterioles directly, and aldosterone causes kidneys to absorb calcium.
4. Two other hormones play a role in maintenance of blood volume.
a. ADH helps increase blood volume by causing the kidneys to reabsorb water.
b. Atrial natriuretic hormone (ANH) causes the excretion of sodium.
1) When the atria of the heart are stretched due to increased blood volume, cardiac cells release ANH.
2) ANH inhibits secretion of renin by kidneys and secretion of aldosterone from the adrenal cortex.
3) When sodium is excreted, so is water; blood volume and pressure decrease.
H. Adrenal Cortex Can Malfunction
1. A low level of adrenal cortex hormones from hyposecretion results in Addison disease.
a. Lack of cortisol results in low glucose levels; a person is subject to stress due to insufficient energy.
b. Lack of aldosterone drops blood sodium levels; the person has low blood pressure and dehydration.
c. Untreated, Addison disease can be fatal.
2. High levels of glucocorticoids from hypersecretion result in Cushing syndrome.
a. Excess cortisol causes a tendency toward diabetes mellitus, a decrease in muscular protein, and an increase in subcutaneous fat resulting in an obese trunk but normal arms and legs.
b. Other symptoms include high blood sodium level, basic blood pH, hypertension, and edema of the face.
c. Women may have masculinization from oversecretion of adrenal male sex hormone.
F. Pancreas Produces Two Hormones (Fig. 49a) [transp. 284]
1. The pancreas is composed of two types of tissue.
a. Exocrine tissue produces and secretes digestive juices into the small intestine by way of ducts.
b. Endocrine tissues called the pancreatic islets (of Langerhans) produce and secrete the hormones insulin and glucagon.
2. All body cells utilize glucose; therefore, its level must be closely regulated.
3. Insulin is secreted when there is a high blood glucose level after eating; insulin has three actions.
a. Insulin stimulates liver, fat, and muscle cells to take up and metabolize glucose.
b. Insulin stimulates the liver and the muscles to store glucose as glycogen.
c. Insulin promotes the buildup of fats and proteins and inhibits their use as an energy source.
4. Glucagon is secreted between meals and in response to low blood glucose level.
a. Effects of glucagon are opposite insulin; it promotes breakdown of stored nutrients and increased blood glucose.
b. Glucagon stimulates the liver to convert glycogen to glucose, raising blood glucose levels.
G. Diabetes Mellitus Is Deficient Insulin
1. Diabetes mellitus is a common disease caused by insulin deficit.
2. Sugar in urine is common laboratory test; it indicates blood glucose level is high enough for kidneys to excrete glucose.
3. Therefore, the liver is not storing glucose as glycogen and the cells are not utilizing glucose for energy.
4. Since carbohydrate is not being metabolized, the body resorts to the breakdown of protein and fat for energy.
5. This builds up ketones in blood; resulting reduced blood volume and acidosis can lead to coma and death.
6. In type I (insulin-dependent) diabetes, the pancreas does not produce insulin.
a. This is thought to result from viral infection that causes cytotoxic T cells to destroy the pancreatic islets.
b. This is treatable with daily administration of insulin; overdose or lack of eating can result in hypoglycemia.
c. The brain has constant sugar requirements; low blood sugar can result in unconsciousness.
d. An immediate intake of sugar is simple treatment.
7. Of 12 million diabetics in U.S., over 10 million have type II (insulin-independent) diabetes.
a. This form of diabetes usually occurs in obese and inactive individuals of any age.
b. The pancreas does produce insulin, but the cells do not respond to it.
c. Initially, this is a result of cells lacking receptors for insulin.
d. Untreated, type II can have serious symptoms: blindness, kidney disease, circulatory disorders, strokes, etc.
e. Low fat diet and regular exercise help; oral drugs make cells more sensitive to insulin or stimulate higher levels of insulin production by pancreas.
H. Testes Are in Males and Ovaries Are in Females
1. The male testes are located in the scrotum, function as male gonads and as endocrine glands; and produce androgens (e.g., testosterone).
a. Testosterone is the male sex hormone.
b. It is responsible for stimulating the development of male secondary sex characteristics.
c. It is required for maturation of sperm.
d. Testosterone is largely responsible for the sex drive and probably aggressiveness.
e. Anabolic steroids are supplemental testosterone or similar chemicals with serious side effects. (Fig. 49.12)
f. Testosterone also affects sweat glands, expression of baldness genes, and other effects.
2. The female sex hormones are estrogen and progesterone.
a. Estrogens secreted at puberty stimulate maturation of the ovaries and other sexual organs.
b. Estrogen is necessary for oocyte development.
c. It is responsible for the development of female secondary sex characteristics including a layer of fat beneath the skin and a larger pelvic girdle.
d. Both estrogen and progesterone are required for breast development and regulation of the uterine cycle.
I. Still Other Endocrine Glands
1. Thymus is most active in children
a. The thymus is a lobular gland that lies in the upper thoracic cavity. (Fig. 49.3) [transp. 280]
b. It reaches its largest size and is most active during childhood; with age, it shrinks and becomes fatty.
c. Some lymphocytes that originate in bone marrow pass through the thymus and are changed into T cells.
d. Thymus produces thymosins, which aid the differentiation of T cells and may stimulate immune cells.
2. Pineal Gland and Daily/Yearly Rhythms
a. The pineal gland produces melatonin.
b. In fishes and amphibians, the pineal gland is near the surface and is a third eye receiving light directly.
c. In mammals, it is located in the third ventricle and cannot receive light directly; it receives nerve impulses from the eyes, by way of the optic tract.
3. The pineal gland and melatonin are involved in establishing circadian rhythms, daily physiological cycles.
4. The pineal gland may also be involved in human sexual development.
a. Some animals go through a yearly cycle of enlargement of reproductive organs when melatonin levels are low.
b. Children in whom a brain tumor has destroyed the pineal gland experience puberty earlier.
5. Melatonin may be involved in seasonal affective disorder where persons are depressed at the onset of winter.
49.3. Environmental Signals in Three Categories (p. 888)
A. Three Categories of Messengers (Fig. 49.13)
1. Pheromones are environmental signals that act at a distance between individual organisms.
a. Ants lay down a pheromone trail for other members to find food.
b. The female silkworm moth releases bombykol that lures a male moth from miles away.
c. Dog urine serves as a territorial marker.
2. Endocrine secretions or hormones are environmental signals that act at a distance between body parts.
a. This also includes the secretions of neurosecretory cells into the hypothalamus.
b. The overlap with the nervous system is illustrated by endorphins that can travel in the bloodstream but act on nerve cells; and norepinephrine is both a neurotransmitter and a hormone secreted by adrenal medulla.
3. Environmental signals can act locally between adjacent cells.
a. Neurotransmitters released by neurons belong to this category.
b. Prostaglandins and growth factors are also called local hormones.
c. Mast cells in the skin release histamines when the skin is cut.
B. Redefinition of a Hormone
1. Traditionally, a hormone was considered to be a secretion of an endocrine gland that was carried in bloodstream to target organs.
2. Recent research has broadened the definition to include all types of chemical messengers.
3. Brain cells can produce insulin.
4. Chemicals identical to hormones have been found in lower organisms; their evolution was a matter of specialization of existing chemical.