The endocrine system consists of ductless
(endocrine) glands that secrete biologically active chemicals called hormones
into the blood or surrounding interstitial fluid. Hormones affect the
metabolism of their target organs and regulation of metabolism, body growth and
reproduction.
Both the
endocrine and nervous systems functions cooperatively in regulating body
processes.
The endocrine system maintains signals and the nervous system receives and
provides signals both externally and internally. For example, violent and
frightful reactions from outside are fed to the eyes and ears through nervous
system to the brain. We respond to those reactions by either running away or
fighting. The nervous system also evokes hormones (epinephrine and
norepinephrine) also called adrenalin to a series of chemical reactions
that responds to this situation both physically and mentally.
The concept of hormone
secretion (primary function of ductless glands) is also extended to include
organs that secrete hormones (including those with ducts). Organs such as skin,
heart, liver, brain and kidneys have been shown recently to secrete hormones in
addition to performing other functions.
This presentation examines
the types of glands and hormones, the pituitary gland and its regulation; other
glands and hormones: adrenal, thyroid and parathyroid, pancreas and others;
mechanism of steroids and thyroxine hormones; mechanism of catecholamines and
polypeptides.
a.
Classification of glands
There are two types of
glands: Exocrine glands that produce non-hormone
secretions (sweat, sebum, saliva) have ducts through which these chemicals are
transferred to the surface. Endocrine glands are ductless glands, that is, they do not have pouches or ducts. Their
secretions enter the tissues, lymphatic or blood vessels around them and are
conveyed to target sites. Local hormones such as autocrines and paracrines
are part considered by some as part of the endocrine system. Autocrines are hormones (e.g.
prostaglandins) that affect the same cells that release them. Paracrine
hormones act locally, however, they exert their
effects away from cells that produce them.
b.
Chemical classification of hormones
There is chemical variation in the hormones secreted
by different glands in the body. However, they all can be grouped under three
general categories:
1.
Catecholamines: mostly water soluble hormones including epinephrine and
norepinephrine
2.
Polypeptides and glycoproteins: they include short chain peptides such as
antidiuretic hormones (ADH), insulin and large glycoproteins such as
thyroid-stimulating hormones.
3.
lipophilic hormones (lipid soluble): they
include steroids such as cortisol and estrogens and thyroxine. All steroid
hormones are derived from cholesterol. The estrogens are produced from the sex
gonads: testes and ovary, which produce testosterone and estradiol
respectively. Thyroxine is a hormone that contains one molecule of
iodine. It is called triiodothyronine when it contains three molecules
of iodine and tetraiodothyronine when it contains four molecules of
iodine.
b.
Similarities between neural and endocrine regulation
There is close association between hormone and
neural regulation of cells. Unlike endocrine system, neurons produce
hormone-like chemical or neurotransmitter, which travels through the blood.
Diffusion across synapse occurs only when gaps are encountered. Hormones and
neuronal chemicals have the following
in common:
1.
presence of specific receptor proteins at the site
2.
Molecules binds to the receptor proteins and produce changes
3.
The chemical must be degraded after its release.
III. HORMONES
MECHANISMS
Hormones produce a response at the target site by
binding to receptor proteins. The binding of hormone molecules to the receptor
may produce one or more of several reactions:
a. changes plasma membrane permeability by
opening
or closing ion gates necessary for action potential
b. promotes synthesis of
protein or regulatory molecules
c.
activate or deactivate enzymes
d. stimulate mitosis
Two mechanisms the binding of lipid soluble steroid
hormones and water soluble peptide hormones to receptors and produce their
response.
1. Steroid
and thyroxine hormones
Steroid and thyroxine are
non-polar lipophilic small molecules. They easily enter their target sites by
combining with carrier proteins. The hormone dissociates from the carrier and
combines with receptor proteins at the target site. The hormone binds to
specific targets on the chromatin or DNA in the nucleus of the cell. The
binding turns on genes initiating transcription and sequent translation of
proteins.
Tetraiodothyronine (T4)
binds to thyroxine binding protein (TBG) where it is transported to the target
site. T4 is enzymatically changed to triiodothyronine (T3).
In side the target T3 is transported to the nucleus by
binding proteins. Inside the nucleus, T3 binds to nuclear
receptor proteins where it induces transcription and subsequently translation.
2. Catecholamines
and polypeptide hormones
Catecholamines (e.g. epinephrine and norepinephrine,
and other amino acid-based hormone) are water-soluble and cannot pass through
the lipid membrane barrier, therefore require a second messenger cyclic AMP
(cAMP). Since these molecules are
water-soluble, they are transported initially by carrier membrane proteins
(also called G-proteins) located on the surface of the cell membrane.
The binding of the hormones to the G-proteins activates an enzyme called adenylate
cyclase, which promotes increased synthesis of cAMP in the cell. Cyclic AMP
activates inactive protein kinases that produce a cascade of cellular
reactions.
·
Generally, all of the effects outline above or anyone of them may be
produced in response to the binding of steroid or thyroxine at the target site.
In addition, here is some properties of hormone
·
Specific receptor proteins are necessary for target cell specificity;
hormones can be up-regulated (increased response) or down-regulated (decrease
response); half-life (time half of the hormone clears from the blood), onset of
activity (time of initiation of activity); duration (how long it remained);
reaction time which involves the following:
1.
Permissiveness: a condition in which of tissues are dependent on the presence of one
or more hormone. For example, the development of reproductive structures is dependent
on the presence of thyroxine hormone.
2.
Synergism: a situation in which two or more hormones produce the same response
but their combined effects are greater than the responses of each hormone
3.
Antagonism: a condition in which the effect of one hormone opposes or suppresses
the effect of another hormone. For example, insulin promotes the uptake of
glucose by lowering blood sugar level. Glucagon opposes this action by
increasing blood glucose level.
Regulation of hormone
release. Control of hormone secretion under negative feedback mechanism of
which there are three categories:
1.
Humoral stimuli: this is a condition in which the secretion of one hormone turns off
another hormone. A good example is insulin and glucagon cited earlier. Another
example is the regulation calcium (Ca++) levels. Low blood
concentration of Ca++ triggers the release of parathyroid hormone
(PTH), which promotes tissue release of Ca++ in to bloodstream.
2.
Neural stimuli: Nerve stimulation regulates hormone secretion. During a fight or
flight situation, the sympathetic nervous system stimulates the adrenal gland
to secrete EPI and NOREPI. These catecholamines directs the fight or flight
reactions during emergency situations.
3.
Hormonal stimuli: hormones stimulate the release and inhibition of other hormones.
These activities occur in many tissues. The release of several hormone of the
anterior or posterior pituitary occurs as a result of stimulation from the
hypothalamus. For example, during thirst condition, the hypothalamus stimulates
the posterior pituitary gland to release antidiuretic hormone (ADH), which
promotes water absorption in the kidneys.
As we drink water, the stretching of the stomach, satiety (fullness)
sends impulse to the hypothalamus which turnoff ADH. This and other negative
feedback mechanisms that control hormone release.
IV.
GLANDS AND SECRETIONS
Endocrine glands consist of specialized cells or
tissues that secrete hormones. Endocrine glands are ductless, therefore their
secretions directly or indirectly enter the blood vessels or through
surrounding lymphatic vessels. Endocrine glands that secrete hormones include:
pituitary, pineal, thymus, thyroid, parathyroid, adrenal, pancreas, stomach and
intestines, gonads and placenta
Pituitary gland (hypophysis)
1. Anatomy:
The pituitary gland is
hanging from the hypothalamic stalk (infundibulum) and secured
within the sella turcica of the sphenoid bone. It consists of two
structures namely: adenohypophysis (anterior), neurohypophysi (posterior).
Anterior pituitary is further divided into two lobes: the pars distalis
(also called anterior pituitary) and pars tuberalis (an extension of
infundibulum), and pars intermedia (located between posterior and
anterior pituitary and present only in fetus).
The anterior pituitary is
connected to the hypothalamus by a network of blood vessels called hypothalamus-hypo
physeal portal system. Through this system, releasing hormones from the
hypothalamus is conveyed to the anterior pituitary. Posterior (neurohypophysis)
has numerous nerve connection blood supply and secretions are under neural
control.
2. Regulation
Hormones
from the anterior pituitary are stimulated by releasing hormones (RIH) from
hypothalamus. Releasing or inhibitory hormones travel locally to the anterior
lobe where they stimulate hormone secretions from the gland. Released hormones
enter systemic circulation until sufficient level is achieved. The hormones are
turned off by a negative feedback mechanism.
The following hormones are secreted from the pars
distalis: ACTH, TSH, FSH, LH, GH and Prolactin. Par
intermedia produces melanocyte-stimulating hormone (MSH). Posterior
pituitary gland produces oxytocin and antidiuretic hormone (ADH).
3. Hormones
a.
Adenocorticortropic hormone (ACTH): Also called corticortropin, this
hormone is controlled by corticortropin releasing hormone (CRH) from the
hypothalamus, which controls its release. The target of ACTH is the adrenal
gland where it stimulates the secretion of glucocorticoids.
b.
Thyroid stimulating hormone (Thyrotropin, TSH): The hormone is controlled by thyroid
releasing hormone (TRH) from the hypothalamus. It stimulates the thyroid
gland to produce thyroid hormones. It is inhibited by thyroid hormones
c.
Growth hormone (GH): GH (also called Somatotropin) stimulates mitosis and
growth of body cells as a result of increased synthesis of proteins and
biological molecules. It also promotes energy metabolism through release of
fats from adipose tissues; use of fats in cellular respiration and conversion
of glycogen to glucose.
Growth hormone releasing
hormone from the hypothalamus stimulates its release and growth hormone
inhibitory hormone (GHIH) inhibits the secretion of growth hormone. Other
stimulants are: low blood sugar level (hypoglycemia), strenuous exercise and excess
of amino acid in blood. Conversely, high levels of blood sugar (hyperglycemia)
stimulate the release of GHIH.
d.
Follicle Stimulating hormone (FSH): This is one of two gonadotropic
hormones secreted by cells of the pituitary gland called gonadotopes and its
targets are the ovaries and testes. In the ovaries it stimulates the
development of eggs and follicles and in the testes, it stimulates
spermatogenesis.
e.
Leutinizing hormone (LH): the second of the two gonadal hormones is produced from gonadotropes
and targeted for the ovaries and testes. It promotes ovulation in females and
LH stimulates the follicle or the yellow body to produce progesterone,
which maintains the pregnancy following ovulation. In males, LH is also called interstitial
cell-stimulating hormone (ICSH), which stimulates the interstitial cells of
the testes to produce testosterone (T). They are released by gonadotropin
releasing hormone (GnRH) and inhibited by sex steroids (estrogen and
testosterone)
f.
Prolactin (PRL): is secreted by lactotropes or mamotropes, which increase greatly
in size during pregnancy. PRL levels rise during pregnancy but have no effect
until the baby is born when it stimulates the mammary glands to synthesize
milk. It remains elevated during the nursing period. In males, PRL make the
testes more sensitive to LH, thus indirectly stimulating secretion of
testosterone.
g.
MSH: this hormone is secreted from the pars
intermdia. It is responsible for stimulating the production of melanin from
melanocytes of the skin. Melanin is responsible for skin pigmentation.
The posterior pituitary (neurohypophysis) produces
two hormones: oxytocin (OT) and antidiuretic hormone (ADH). The
pituitary has an extensive array of nerve connections therefore its secretions
are indirectly regulated by neural impute from the hypothalamus.
Unlike the anterior pituitary, which relies on
releasing hormones, the posterior pituitary stores and secretes these hormones
from cells of the supraoptic and paraventricular neuclei of the hypothalamus
and transported by the hypothalamohyposeal tract. These tracts directly
connect to the blood vessels. The effects of OT and ADH.
a.
Oxytocin (OT): Large amounts of this hormone are released during childbirth,
which stimulates and strengthen the smooth muscles of the uterus. It also
affects the mammary glands, stimulating the oxytocin release when the
baby sucks the nipples, which in turn contracts the mammary glands causing them
to secrete milk.
b. Antidiuretic hormone (ADH): This hormone is also called vasopressin. It
promotes the retention of water by the kidneys by preventing less excretion of
water in urine-increased retention in blood. It also promotes vasoconstriction
in some animals (this effect remains controversial).
These
glands are located on top of the kidneys and contain an outer cortex and an
inner medulla. The cortex is divided into three zones: zona glomerulosa,
middle zona fasciculate and an inner zona reticularis. The medulla derived from the neural crest
consists of chromaffin cells innervated by sympathetic fibers. The cortex is
derived from the embryonic mesoderm. Functionally they are different.
Adrenal
Cortex:
Secretes
steroid hormones called corticorsteroids which consist of three steroid
hormones:
1.
Mineralocorticoids: regulate Na+ and K+ balance in kidneys. The
most potent of the mineralocorticoids, aldosterone (secreted by zona
glomerulosa) promotes Na+ retention in the kidneys.
2.
Glucocorticoids: regulate metabolism of glucose and other organic molecules. Cortisol
(hydrocortisone) is the predominant of the glucocorticoids. It is secreted from
zona fasciculate and zona reticularis. Secretion of ACTH and cortisol are
caused by stress.
3.
Sex steroids: weak androgens and small amounts of estrogen
The chromaffin cells of the medulla, innervated by
the sympathetic nerves secrete epinephrine (EP) and norepinephrine (NEP),
producing typical sympathetic effects. Many stressors activate the adrenal
medulla as well as the cortex, preparing the body for maximal mental and
physical performance (the fight or flight reaction).
Thyroxine helps regulate the metabolic rate,
necessary for growth and development; formation of reproductive structures;
parathyroid hormone regulate calcium metabolism in blood.
The thyroid gland is located below the larynx and in
front of the trachea. It consists of two lobes called isthmus and the largest
of the endocrine gland, weighing 25g. It consists of sacs called thyroid
follicles lined with cuboidal epithelia follicular cells. These follicular
cells secrete thyroxine. Between the follicular cells are
Thyroxine,
T3 and T4
Three thyroid hormones are secreted. Thyroxine,
triiodothyronine (T3) contains three molecules of iodine and
tetraiodothyronine (T4) contain four molecules of iodine. Both T3
and T4 synthesis are dependent on iodine (I) presence. These hormones have similar effects: they
increase metabolic rate, promote growth and cell division, and promotes protein
synthesis, metabolism of fat and carbohydratres.
Calcitonin: The third
hormone produced from the thyroid gland functions in lowering blood calcium
level by stimulating the uptake and deposition of calcium ions by osteoblast cells.
The function of this hormone is antagonistic to that of parathormone
produced from parathyroid gland.
Parathyroid hormone (PTH): PTH is secreted from parathyroid gland. PTH
regulates low blood calcium levels by stimulating osteoclast cells to
demineralize bone, inhibiting the secretion of calcium ions by the kidneys and
promoting the absorption of calcium ions by the intestines, thus releasing
calcium ions into the blood. The antagonistic action of PTH and calcitonin
maintains blood calcium homeostasis.
The pancreas is both an exocrine and endocrine
gland. As an exocrine gland, small secretory cells that produce digestive
enzymes merge to form pancreatic ducts, which secrete enzymes and digestive
juices. As an endocrine gland, clusters
of cells called Islet of Langerhans secrete directly enter the blood
stream. The Islet of Langerhans contains
alpha cells and beta cells. The beta cells secrete insulin and
the alpha secretes glucagon. The actions of insulin and glucagon are antagonist
to one another.
a. Insulin
The
beta cells produce insulin in response to rising level of blood glucose. When
blood glucose level is high insulin is secreted which stimulates the uptake of
glucose by hepatocytes. Glucose is then converted into glycogen and stored in
the liver and also in the muscle tissues and in adipose as fat. Insulin also
promotes amino acid utilization and cellular protein synthesis.
b. Glucagon:
The threshold for low blood glucose level is 180 mg/dL.
The brain relies on blood glucose for its energy. When glucose concentration
falls below the threshold value, the brain sends signals (pain/headache,
dizziness, etc) indicating low blood sugar level. Our body responds when the
alpha cells secrete glucagon that converts stored glycogen in the liver and
muscle into glucose and release it to the blood stream. The rising blood
glucose level turns off the hormone stimulus. These actions of insulin and
glucagon maintain the blood glucose homeostasis.
Pineal body or gland is located in the third
ventricle where it is covered by the meringues of the brain. The size of this
pine cone-shaped gland maximum between age 1 and 5 and regresses in adolescent
to a mere shrunken fibrous tissue mass. In animals with seasonal breeding, it
regulates the breeding cycle and the gonads.
It produces Serotonin by day
and converts it to melatonin by night. Melatonin suppresses gonadotropin and
removal of pineal gland result in premature sexual maturation. Excessive
secretion of melatonin is associated with a delay in onset of puberty. The role
of melatonin remains controversial.
The gonads (testes and ovaries) secrete sex
steroids. These include male sex hormones or androgens and female sex hormones-
estrogens and progesterone. The principal hormones in each of these categories
are testosterone, estradiol-17B and progesterone.
The placenta is the organ responsible for nutrient
and waste exchange between the fetus and the mother. It is also an endocrine gland that secretes
large amounts of estrogen and progesterone as well as other peptides.
There are a few disorders associated with hormones
function. A few of the hormones with widespread disorders are examined.
1. Antidiuretic hormone (ADH)
A severe hyposecretion of ADH may result in diabetes
insipidus, a condition characterized by production of excessive quantities
(20-30 liters) of dilute urine
2. Thyroid gland disorders: hypersecretion, hyposecretion,
iodine deficiencies produce exophthalmic goiter, simple goiter, cretinism,
myxedema.
a. Exophthalmic goiter (Grave’s disease) is a
condition that results from hypersecretion of thyroxine (and T3). It
is characterized by increased metabolic rate, restlessness, weight loss,
bulging eyes and swelling of the thyroid gland
b. Simple goiter: This is the enlargement of
the thyroid gland and result from a deficiency of iodine in the diet. Without
iodine, inadequate amount of thyroxine and T3 are produced and the
gland enlarges in an attempt to produce more hormones. Goiter can be prevented
by inclusion of adequate amount of iodine in diet (e.g. iodized salt) or
iodized spices.
c. Cretinism: this is caused by a severe
deficiency of thyroxine and T3 in infants. Without treatment it
results in mental and physical retardation. It is characterized by stunted
growth, abnormal bone formation, mental retardation and sluggishness.
d. Myxedema: Caused by severe thyroxine
and T3 deficiency in adults and characterized by weight gain,
weakness, dry skin, puffiness of the face and sluggishness.
3. Parathyroid
hormone:
a. Hypoparathyroidism: Insufficient secretion of para- thyroid
hormone may result in drastic drop in the concentration of blood calcium ions.
Untreated this may produce calcemic tetany (inability of the muscles to
contract) thus resulting in death.
b. Hyperparathyrodism: Excessive secretion of
this hormone may result in excessive removal of calcium ions from bones
resulting in high blood calcium ions.
Untreated this condition may lead to osteoporosis, kidney stones and
bone formation in abnormal areas of the body.
4. Adrenal
Cortex
a. Cushion’s syndrome (cortisol or aldosterone):
Hyper secretion of either of these hormones may produce Cushion’s syndrome
characterized by high blood pressure, protein loss, osteoporosis, accumulation
of fat on the trunk, fatigue, edema, and decreased immunity. A person with this
condition tends to have a full rounded face.
c. Addision’s disease: This condition results from
a severe hyposecretion of either cortisol or aldosterone by the adrenal cortex.
Low blood pressure, low blood sugar and sodium levels, an increase in potassium
level, dehydration, muscle weakness and increased skin pigmentation
characterize it. May result in death without treatment.
5. Insulin
a. Diabetes mellitus: Caused by insufficiency or
hypo- secretion of insulin. It is characterized by high level of blood glucose.
The hepatocytes are not able to take up glucose therefore such individuals
cannot metabolize glucose. They rely on fat for energy. When fat is metabolized
as energy it produces keto acids which tends to lower the blood pH (acidosis)
thus inactivating enzymes and may be fatal. There are two types of diabetes:
Type I (insulin-dependent)
diabetes appears in individuals less than 20 years and persist throughout life.
Individuals require frequent insulin injections to counter insulin deficiency.
Type II (non-insulin independent) diabetes occurs in individuals over 40 years
and overweight. This type of diabetes may be controlled by diet and medication.
b. Hypoglycemia: An extremely low level of blood glucose
sometimes within 30min to 60 min after eating. Food craving and lethargy may
characterize the condition immediately after eating. It may be caused by
hyperactive beta cells of Langerhans that puts out excessive amounts of
insulin.
6. Growth
hormone
a. Acondroplasia (dwarfism): results from
inadequate secretion of growth hormone (Somatotropin) during birth. Early
detection may remedy the condition by injection of the hormone.
b. Cachexia: in adults inadequacy of GH
produces cachexia (premature aging) caused by tissue atrophy.
c. Gigantism: oversecretion of GH leads
to excessive stimulation of the epiphyseal plates leading to abnormal increase
in bone lengths.
d. Acromegly: In adults hypersecretion
leads to softening disfiguring of the bones especially bones of the face, hand
and feet.