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The Endocrine System
The hormones of the endocrine system regulate the physiologic and metabolic activities and growth of
target cells in the body.
Comparison of Control by the Nervous and Endocrine Systems
The nervous and endocrine systems act together to coordinate functions of all body systems. Nervous
system acts through nerve impulses conducted along axons of neurons. At synapses, nerve impulses
trigger the release of chemical mediators, the neurotransmitters. The endocrine system releases
mediators, the hormones.
The control of the two systems is different.
Responses of the endocrine system are slow acting and prolonged, compared to the responses of the
nervous system. Although some hormones act within seconds most take several minutes or more to
cause a response. Effects of nervous system activation are generally briefer than those of the endocrine
system. The nervous system acts on specific muscles and glands. The influences of the endocrine
system are broader and regulate virtually all types of body cells.
A hormone is a mediator molecule that is released in one part of the body but regulates the activity of
cells in other parts of the body. The circulating blood delivers hormones to cells throughout the body.
Both neurotransmitters and hormones exert their effects by binding to receptors on or in their target
cells. Several mediators act as both neurotransmitters and hormones.
Endocrine glands
Endocrine glands secrete their products (hormones) into the interstitial fluid from the secretory cells
that produced the hormones. From the interstitial fluid, hormones diffuse into capillaries and the blood
carries them to target cells throughout the body. The circulating concentrations of the hormones are
low.
Functions of Hormones
1.
Help regulate:
 Chemical composition and volume of internal environment (interstitial fluid)
 Metabolism and energy balance
 Contraction of smooth and cardiac muscle fibers
 Glandular secretions
 Some immune system activities.
2.
3.
4.
Control growth and development.
Regulate operation of reproductive systems.
Help establish circadian (day-night) rhythms.
Control of Hormone Secretion
The release of most hormones occurs in short bursts, little or no secretion between bursts. Regulation
of secretion normally prevents overproduction or underproduction of the hormones.
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Hormone secretion is regulated by the nervous system, chemical changes in the blood, and other
hormones. Most hormonal regulatory systems work via negative feedback, few operate via positive
feedback.
Hypothalamus and Pituitary Gland
Hypothalamus
The hypothalamus a small region of the brain below the thalamus is the major link between the
nervous and endocrine systems. The hypothalamus receives input from the limbic system, cerebral
cortex, thalamus, and reticular activating system, sensory signals from internal organs and from the
retina.
The hypothalamus in the nervous system is an important regulatory center of the endocrine system as
well as an endocrine gland itself. The hypothalamus (9) and the pituitary gland (7) secrete 16
hormones which play important roles in the regulation of virtually all aspects of growth, development,
metabolism and homeostasis.
Pituitary Gland
The pituitary gland is a pea-shaped structure that lies in the sella turcica of the sphenoid bone. It
attaches to the hypothalamus by the infundibulum and has two anatomically functionally separate
lobes. Anterior pituitary (anterior lobe) or adenohypophysis (adeno- means gland) consists of two
parts, the pars distalis and the pars tuberalis. The posterior pituitary (posterior lobe) or
neurohypophysis also consists of two parts the pars nervosa and the infundibulum. Posterior pituitary
contains axons and axon terminals of neurons whose cell bodies are located in the hypothalamus.
A third region of the pituitary gland called the pars intermedia.
Anterior Pituitary
The anterior pituitary or adenohypophysis secretes hormones that regulate activities from growth to
reproduction. Release of anterior pituitary hormones is stimulated by releasing hormones and
suppressed by inhibiting hormones from the hypothalamus. Hypothalamic hormones are an important
link between the nervous and endocrine systems.
Hypophyseal Portal System
Hypothalamic hormones reach the anterior pituitary through a portal system. In a portal system blood
flows from one capillary network into a vein then into a second capillary network without passing
through the heart. In the hypophyseal portal system blood flows from capillaries in the hypothalamus
into portal veins in the infundibulum that carry blood to capillaries of the anterior pituitary.
Specialized neurons, called neurosecretory cells, synthesize the hypothalamic releasing and inhibiting
hormones. The hormones then diffuse into the hypophyseal portal system. This direct route permits
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hypothalamic hormones to act immediately on anterior pituitary cells, before the hormones are diluted or
destroyed in the general circulation. Hormones secreted by anterior pituitary cells pass into capillaries,
then drain into veins and out into the general circulation to target tissues throughout the body. Hormones of
the anterior pituitary gland that influence other endocrine glands are called tropic hormones or tropins.
Control of Secretion by the Anterior Pituitary
Secretion of anterior pituitary hormones is regulated in two ways. 1. Neurosecretory cells in the
hypothalamus secrete five releasing hormones which stimulate secretion of anterior pituitary hormones
and two inhibiting hormones which suppress secretion of anterior pituitary hormones. 2. Negative
feedback of the hormones released by target glands decreases secretions anterior pituitary cells. In such
negative feedback loops the secretory activity decreases when blood concentrations of their target
gland hormones rise.
Human Growth Hormone and Insulin-like Growth Factors
Human growth hormone (hGH) or somatotropin is the most plentiful anterior pituitary hormone. Main
function of hGH is to promote synthesis and secretion by the cells of the body of small protein
hormones called insulin-like growth factors (IGFs) or somatomedins. IGFs cause cells to grow and
multiply by increasing protein synthesis. Due to the effects of the IGFs and hGH there is an increase
the growth rate of the skeleton and skeletal muscles during childhood and the teenage years. In adults,
IGFs and hGH help maintain the mass of muscles and bones and promote tissue repair. Low blood
glucose circulating to the hypothalamus promotes release of GHRH to cause release of hGH. High
blood glucose circulating to the hypothalamus stimulates release of GHIH to inhibit release of hGH.
Thyroid-Stimulating Hormone
Thyroid-stimulating hormone (TSH) stimulates the synthesis of the two thyroid hormones,
triiodothyronine (T3) and thyroxin (T4) by the thyroid gland. Thyrotropin-releasing hormone (TRH)
from the hypothalamus controls TSH secretion. Release of TRH and TSH depends on blood
concentrations of T3 and T4 via negative feedback.
Follicle-Stimulating Hormone
In females, the ovaries are the targets for follicle-stimulating hormone (FSH). FSH initiates the
development of several ovarian follicles, a spherical arrangement of secretory cells that surround a
developing oocyte. FSH also stimulates follicular cells to secrete estrogens. In males, FSH stimulates
sperm production in the seminiferous tubules of the testes. Gonadotropin-releasing hormone (GnRH)
from the hypothalamus stimulates FSH release.
Luteinizing Hormone
In females, luteinizing hormone (LH) triggers ovulation of a secondary oocyte (future ovum) by an
ovary. LH stimulates formation of the corpus luteum from the ovulated follicle and secretion of
progesterone by the cells of the corpus luteum. FSH and LH also stimulate secretion of estrogens by
the corpus luteum cells. Estrogens and progesterone prepare the uterus for implantation of a fertilized
ovum and help prepare the mammary glands for milk secretion. In males, LH or interstitial cell
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stimulate hormone (ICSH) stimulates the interstitial cells of the testes to secrete testosterone.
Secretion of LH is controlled by gonadotropin-releasing hormone (GnRH). Release of GnRH, FSH and
LH is suppressed by estrogens and testosterone through negative feedback systems.
Prolactin
Prolactin (PRL) along with other hormones initiates and maintains milk secretion by the mammary
glands. Ejection of milk from the mammary glands depends on oxytocin released from the posterior
pituitary. Milk secretion and ejection constitute lactation.
Adrenocorticotropic Hormone
Adrenocorticotropic hormone (ACTH) controls the production and secretion of glucocorticoids by the
cortex (outer portion) of the adrenal glands. Corticotropin-releasing hormone (CRH) from the
hypothalamus stimulates secretion of ACTH by corticotrophs. Glucocorticoids inhibit CRH and
ACTH release via negative feedback.
Posterior Pituitary
The posterior pituitary or neurohypophysis does not synthesize hormones. It stores and releases two hormones
oxytocin (OT) and antidiuretic hormone (ADH) or vasopressin. The posterior pituitary consists of axon
terminals of hypothalamic neurosecretory cells. The cell bodies of the neurosecretory cells are in the
hypothalamus and the axons form hypothalamic-hypophyseal tract in the infundibulum. This tract begins in
the hypothalamus and ends in the posterior pituitary.
The cell bodies of neurosecretory cells produce the OT and ADH in secretory vesicles. The vesicles
then move through the axons to the axon terminals in the posterior pituitary where they are stored until
nerve impulses trigger release of the hormones.
Oxytocin
During and after delivery of a baby, OT affects two target tissues; the mother’s uterus and breasts.
During delivery, OT enhances contraction of smooth muscle in the wall of the uterus. After delivery,
OT stimulates milk ejection (“letdown”) from the mammary glands in response to the mechanical
stimulus provided by the sucking of the infant on the nipple.
Antidiuretic Hormone
ADH causes the kidneys to return more water to the blood, thus decreasing urine volume. ADH also causes
constriction of arterioles which increases blood pressure. This is why it is also called vasopressin.
Thyroid Gland
Spherical sacs called thyroid follicles make up most of the thyroid gland. The follicular cells produce
two hormones of the thyroid gland thyroxin or tetraiodothyronine (T4), contain four atoms of iodine
and triiodothyronine (T3), contains three atoms of iodine. Parafollicular cells or C cells, which lie
between follicles, produce calcitonin.
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Actions of Thyroid Hormones
T3 and T4 exert their effects throughout the body.
1. Thyroid hormones increase basal metabolic rate (BMR) by stimulating the use of cellular oxygen to
produce ATP by increasing the metabolism of carbohydrates, lipids and proteins.
2. As cells use more ATP, more heat is given off, and body temperature rises this is a calorigenic
effect of the thyroid hormones.
Calcitonin
The hormone produced by the parafollicular cells of the thyroid gland is calcitonin (CT). CT decreases
the concentration of calcium in the blood by inhibiting the action of osteoclasts, the cells that break
down bone extracellular matrix.
When Ca2+ ion blood concentration is high, calcitonin lowers the amount of blood calcium by
inhibiting bone resorption (breakdown of bone extracellular matrix) by the osteoclasts and accelerating
uptake of calcium into bone extracellular matrix.
Parathyroid Gland
Parathyroid Hormone or Parathormone
Parathyroid hormone (PTH) is the major regulator of the concentrations of calcium Ca2+ and phosphate
(HPO42-) ions in the blood. Action of PTH is to increase the number and activity of osteoclasts. The result is
elevated bone resorption, which releases ionic calcium (Ca2+) and HPO42- into the blood. PTH also acts on
the kidneys in 3 ways. 1. PTH slows the rate at which Ca2+ ions is lost into the urine so increases blood Ca2+
ion concentration. 2. PTH increases loss of HPO42- ions into the urine. 3. PTH promotes formation of the
hormone calcitriol, the active form of vitamin D. Calcitriol increases the rate of Ca2+ion absorption from the
GI tract into the blood.
The blood calcium concentration directly controls the secretion of both calcitonin and PTH by negative
feedback loops that do not involve the pituitary gland.
1. A higher than normal concentration of (Ca2+) ions in the blood stimulates parafollicular cells of the
thyroid gland to release more calcitonin.
2. Calcitonin inhibits the activity of osteoclasts, thereby decreasing the blood Ca2+ ion concentration.
3. A lower than normal concentration of Ca2+ ions in the blood stimulates chief cells of the parathyroid
gland to release more PTH.
4. PTH promotes resorption of bone extracellular matrix, which releases Ca2+ions into the blood and
slows loss of Ca2+ ions in the urine, raising the blood concentration of Ca2+ ions.
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5. PTH also stimulates the kidneys to synthesize calcitriol, the active form of vitamin D.
6. Calcitriol stimulates increased absorption of Ca2+ ions from the GI tract which helps increase the
blood concentration of Ca2+ ions.
Adrenal Glands
Adrenal Cortex
The adrenal cortex is subdivided into three zones, each of which secretes different hormones. The outer
zone, zona glomerulosa secrete mineralocorticoids hormones because they affect mineral homeostasis.
The middle zone, zona fasciculata secrete mainly glucocorticoids hormone because they affect glucose
homeostasis. The inner zone, zona reticularis, secretes androgens, which have masculinizing effects.
Mineralocorticoids
Aldosterone the major mineralocorticoid regulates homeostasis of two mineral ions Na+ and K+ ions
and helps adjust blood pressure and blood volume. The renin-angiotensin-aldosterone (RAA) pathway
controls secretion of the aldosterone.
Glucocorticoids
The glucocoticoids regulate metabolism and resistance to stress are cortisol (hydrocortisone),
corticosterone and cortisone. Cortisol is the most abundant.
Glucocorticoids have the following effects:
1. Protein breakdown - Glucocorticoids increase the rate of protein breakdown. The amino acids
formed are then used for synthesis of new proteins or for ATP production.
2. Gluconeogensis (glucose formation) - Upon stimulation by glucocorticoids, liver cells convert
certain amino acids and lactic acid to glucose.
3. Lipolysis - Glucocorticoids stimulate lipolysis, the breakdown of triglycerides and release of fatty
acids from adipose tissue into the blood.
4. Resistance to stress - Glucocorticoids promote resistance to stress, as the additional glucose
provides tissues with a ready source of ATP.
5. Anti-Inflammatory effects - Glucocorticoids inhibit white blood cells that participate in
inflammatory responses.
6. Depression of immune responses - Glucocorticoids depresses immune responses. Glucocorticoids
are prescribed for organ transplant recipients to retard tissue rejection by the immune system.
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Androgens
In both males and females, the adrenal cortex secretes small amounts of androgens. The amount of
androgens secreted by the adrenal gland is usually so low that their effects are insignificant. In
females, adrenal androgens promote libido (sex drive) and are converted into estrogens (feminizing sex
hormone) by other body tissues. After menopause all estrogens come from conversion of adrenal
androgens.
Adrenal medulla
The inner region of the adrenal gland, the adrenal medulla, is a sympathetic ganglion of the autonomic
nervous system (ANS). The two major hormones synthesized by the adrenal medulla are epinephrine
(E) and norepinephrine (NE). The medullary hormones intensify sympathetic responses in other parts
of the body. These hormones increase heart rate and force of contraction, which increases blood
pressure and increases blood flow to the body organs.
Pancreatic Islets
The pancreas is both an endocrine and exocrine gland. Scattered among the exocrine acini are
pancreatic islets, the islets of Langerhans.
Cell Types in the Pancreatic Islets
1. Alpha (α) cells constitute about 17% of pancreatic islet cells and secrete glucagon.
2. Beta (ß) cells constitute about 70% of pancreatic islet cells and secrete insulin.
Glucagon raises blood glucose concentration and insulin lowers it.
Regulation of Glucagon and Insulin Secretion
The principal action of glucagon is to increase blood glucose concentration when the blood glucose
concentration falls below normal. Insulin helps lower blood glucose concentration when the blood
glucose is too high. The concentration of blood glucose controls secretion of glucagon and insulin via
negative feedback without intervention of pituitary tropic hormones.
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Disorders of the Endocrine System
Disorders of the endocrine system involve hyposecretion, inadequate release of a hormone or
hypersecretion, excessive release of a hormone.
Pituitary Gland Disorders
Pituitary Dwarfism, Giantism, and Acromegaly
Disorders of the anterior pituitary involve human growth hormone (hGH). Hyposecretion of hGH
during the growth years slows bone growth and the epiphyseal plates close before normal height is
reached. This condition is pituitary dwarfism.
Hypersecretion of hGH during childhood causes giantism, abnormal increase in the length of long
bones. Person grows to be very tall, body proportions are normal. Hypersecretion of hGH during
adulthood is called acromegaly, the bones thicken and other tissues enlarge, body proportions are
abnormal.
Diabetes Insipidus
Diabetes insipidus is an abnormality associated with dysfunction of the posterior pituitary due to
hyposecretion of ADH, thus a great volume of water is lost in the urine.
Thyroid Gland Disorders
Congenital hypothyroidism, hyposecretion of thyroid hormones that is present at birth is termed
cretinism. Cretinism causes severe mental retardation and stunted bone growth.
Hyperthyroidism is Graves’s disease. Graves’s disease is an autoimmune disorder in which the person
produces antibodies that mimic the action of thyroid-stimulating hormone (TSH). The antibodies
continually stimulate the thyroid gland to grow and produce thyroid hormones causing an enlarged
thyroid gland.
Parathyroid Gland Disorders
Hypoparathyroidism (low PTH concentration) leads to a deficiency of blood Ca2+ ions, which causes
neurons and muscle fibers to depolarize and produce action potentials spontaneously. This leads to
twitches, spasms, and tetany (maintained contraction) of skeletal muscle.
Hyperparathyroidism (high PTH concentration) causes excessive resorption of the bone matrix, raises
the blood concentrations of Ca2+ and HPO42- ions and causes bones to become soft and easily fracture.
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Adrenal Gland Disorders
Cushing’s Syndrome
Cushing’s syndrome is due to hypersecretion of cortisol by the adrenal cortex. The elevated
concentration of cortisol causes hyperglycemia, osteoporosis, weakness, hypertension, increased
susceptibility to infection, decreased resistance to stress and mood swings.
Addison’s Disease
Hyposecretion of glucocorticoids and aldosterone causes Addison’s disease (adrenocortical
insufficiency). Addison’s disease is an autoimmune disorder in which antibodies cause adrenal cortex
destruction or block binding of ACTH to its receptors.
Pancreatic Islet Disorders
Diabetes mellitus is the endocrine disorder caused by an inability to produce or use insulin. Because
insulin is unavailable to aid transport of glucose into body cells, blood glucose concentration is high
and glucose “spills” into the urine (glucosuria). Diabetes mellitus causes polyuria, excessive urine
production due to an inability of the kidneys to reabsorb water; polydipsia, excessive thirst and
polyphagia, excessive eating.
There are two types of diabetes mellitus.
Type 1 diabetes, insulin-dependent diabetes mellitus (IDDM) the insulin concentration is low because
the person’s immune system destroys the pancreatic ß cells.
Type 2 diabetes, non-insulin-dependent diabetes mellitus (NDDM) most often occurs in obese people.
Type 2 diabetic individual has a sufficient amount (or even a surplus) of insulin is in the blood. The
diabetes is caused by target cells of the body become less sensitive to the insulin.
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