Endocrinology is a branch of
medical science that deals with the study of glands and their secretions known
as hormones. It also studies the clinical disorders associated with
hypersecretion and hyposecretion of hormones that the gland has produced and
the possible therapy or treatment to correct the abnormalities manifested
through laboratory diagnosis.
The term gland is given to any part of
the body that develops secretion. There are two types of glands – the exocrine
and the endocrine glands.
Exocrine glands are
usually called glands of external secretion because their secretions
are eliminated through ducts and are usually utilized for special functions in
a particular region rather than throughout the entire body. Among them are the
salivary glands that pour saliva into the mouth and the mammary glands that
produce milk. Glands of this type secrete also the digestive juices of the
stomach and the bile of the liver.
Endocrine glands are groups of
specialized body cell which extract materials from the blood stream and convert
them into hormones which are then secreted directly into the blood stream and
carried into every living body cell. Since the hormones are poured into the
blood without passing through an excretory canal or duct, these glands are also
called glands of internal secretion or ductless glands.
The endocrine and nervous system
function to achieve and maintain homeostasis. When the two systems work
together, referred to as neuroendocrine system, they perform the same general
functions: communication, integration and control.
HORMONES
A. Definition
1. Any substance
normally produced by specialized cells in some part of the body and carried by
the bloodstream to another part from which it affects the body as a whole.
Example, ACTH is secreted by the pituitary but it effects the functional
activities of the adrenal cortex
2. Chemical
substances that are formed in one organ and exert their influence on other
organs or tissues, the physiologic effect of the hormone is such that it acts
the bridge of the chemical communication system.
3. Hormones which
inhibit activity are called chalones.
B. General characteristics of hormones
1. Produced
specifically by certain type of cell.
2. Secreted
directly into the blood stream or interstitial fluid.
3. Provoke
specific activity in other organs susceptible to their effects; do not create
additional effects.
4. None of them
is secreted at a precisely uniform rate.
5. Hormones are
continually lost to the body either by process of metabolic inactivation or by
excretion.
6. Active in
minute amounts; does not contribute energy or matter in significant amounts; do
not initiate chemical reactions but alter the rates of pre–existing reactions.
C. Functions of hormones
1. Regulatory
function
– metabolism of salts, water, carbohydrates, fat and proteins is maintained by
secretion of appropriate hormones.
2. Morphogenesis – development
of male and female sex characteristics which are under the influence of the
respective sex hormone
3. Integrative action – each
hormone has specific action and function. Although a particular hormone
dramatically influences a single biochemical event, or dramatically changes the
morphology and rate of metabolism of a single organ, the presence of other
hormones produced by different endocrine glands is also important for efficient
functioning.
D. Regulation of hormone secretion
Control of
hormonal secretion is usually part of negative feedback loop and is called
endocrine reflexes. This regulation is accomplished through series of servo
feedback systems. A feedback system is a system in which the function of one
variable (A) affects the function of another variable (B). If B increases as A
increases, the relationship is described as positive feedback but
if an increase in A that causes a decrease in B is described as negative
feedback.
E. General principle of hormone action
1. Hormones
signal a cell by binding to the target cells’ specific receptors in a “lock and
key” mechanism.
2. Different
hormone–receptor interactions produce different regulatory changes within the
target cell through chemical reactions.
3. Combined
hormone action
a. Synergism –
combinations of hormones acting together have a greater effect on target cell
than the sum of the effects that each would have if acting alone
b. Permissiveness – when a
small amount of one hormone allows a second one to have its full effect on a
target cell.
c. Antagonism – one hormone
produces the opposite effects on another hormone; used to “fine tune” the
activity of target cells with great accuracy.
4. Endocrine
glands produce more hormone molecules than actually are needed; the unused
hormones are quickly secreted by the kidneys or broken down by metabolic
processes.
F. Types of hormone action
1. Paracrine – hormones
synthesized act locally on cells other than those that produce them.
Example: release of somatostatin
from islet delta cells and its
subsequent
action on nearby alpha and beta cells in the
pancreatic islet.
2. Autocrine – hormone
synthesized act on cell where it is produced.
Example: action of somatostatin
on its own secretion
3. Neuroendocrine – hormone
synthesized in nerve endings and released into extracellular space, interacts
with receptors of cells at distant site.
4. Neurocrine – hormone
synthesized in neurons and released into extracellular space; binds to receptor
in nearby cell and affects its function.
Example: action of cardiac muscle cells of
neuroepinephrine
synthesized in
nerve endings in the heart.
5. Neurotransmission – hormone
synthesized in nervous and released from nerve endings; crosses synapse and
binds to specific receptors in another neuron, affecting its action.
Example: release of acetylcholine from
preganglionic nerve fibers in
sympathetic
ganglia and binding to receptor in
postganglionic
neuron with liberation of norepinephrine
G. Transport, metabolism and excretion of hormones
Hormones exist
in the plasma in two forms: Free State and bound form. Relatively small amounts
are present in free form; majority is bound form.
Bound
form – certain hormones are transported largely in combination with
plasma
proteins
Example:
Estrogens and androgens bound to
albumin
Corticosteroids bound to
corticosteroids binding globulin
Thyroxine bound to thyroxin–binding
globulin
Protein–bound
complex – relatively non–diffusible
–
this restricts passage of hormone across glomerular capillaries into the liver.
–
this restricts the passage of the hormone across other capillaries, thereby limiting the amount of
hormone coming into direct
contact
with cells of various cells.
–
physiologically inactive
Binding by
plasma protein is a regulatory mechanism, protecting the organism sudden and
undesirable fluctuations in concentrations of circulating hormone.
H. Concentration of hormone in blood
Since a
hormone is transported to its target via blood, its concentration in the blood
reflects its functions. If a hormone is to have an effect, it must achieve a
certain threshold in the blood, although this threshold usually is quite low.
As a consequence, conditions which alter the blood level of a particular hormone
have a modifying effect on the function which is under the control of that
particular hormone.
Several
factors which determine the concentration of a hormone in the blood:
1. The rate of
secretion – the faster a hormone is released into the blood, the higher its
concentration level will be, if all other conditions, which affects its blood
concentration remain constant. The reverse is also true, the slower the
secretion, the lower the hormonal concentration. The rate of secretion of a
hormone is usually under the control of a negative feedback mechanism.
Once a hormone
has carried out its task; it must be removed from the blood, otherwise, it will
continue to produce its effect and therefore lose its regulatory capacity.
There are several things the body can do to rid of unwanted hormone:
a. One way is to
simply excrete them with the urine either directly or in modified form.
b. Another is to
convert them chemically into an active form. The liver usually performs this
task.
2. One more important
factor which affects the performance level of hormones in the blood is that not
all hormones are soluble enough in the blood to travel by themselves so they
must travel in association with plasma proteins, otherwise, they will be unable
to reach their target tissues.
I. Disorders of the endocrine system
1. Primary disorders – involve
some problem with the gland that produces the hormone (either hypersecretion or
hyposecretion), eventhough the outside stimulating agents are normal.
2. Secondary disorders – the gland
that produces the hormone is capable of normal function. The outside
stimulating agents either are in excess (resulting in glandular hypersecretion)
or are deficient (resulting in glandular hyposecretion).
a. Hypersecretion
is treated by inducing hyposecretion
b. Hyposecretion
is often not detected until approximately 90% of the gland is non–functional.
The treatment for hyposecretion usually involves hormone replacement therapy.
J. Types of hormones
1. According to general function
a. Tropic hormones – hormones
that target other endocrine glands and stimulate their growth and secretion.
b. Sex hormones – hormones
that target reproductive tissues.
c. Anabolic hormones – hormones
that stimulate anabolism in target cells.
2. According to chemical structure
a. Steroid hormones – synthesized
from cholesterol, lipid soluble and can easily pass through the phospholipid
plasma membrane of target cells. They possess a common structural nucleus
consisting of 4 rings and 17 carbon atoms and is known as cyclopentanoperhydrophenanthrene nucleus as
shown below:
Mechanism of
action:
(1) Steroid
hormones are lipid soluble and their receptors are normally found in the target
cells’ cytoplasm.
(2) Once a steroid
hormone molecule has diffused into the target cell, it binds to a receptor
molecule to form a hormone–receptor complex.
(3) Mobile–receptor
hypothesis
– the hormone–receptor complex migrates into the nucleus and it activates a
certain gene sequence to begin transcription of mRNA; newly formed mRNA
molecules move into the cytoplasm, associate with ribosomes and begin
synthesizing protein molecules.
(4) Steroid
hormones regulate cells by regulating production of certain critical proteins.
(5) The amount of
steroid hormone present determines the magnitude of a target cells’ response.
(6) Since the
transcription and protein synthesis takes time, response to steroid hormones
are often slow.
b. Non–steroid hormone – hormones
synthesized primarily from amino acids.
(1) Protein hormones – long,
folded chains of amino acids; e.g., insulin and parathyroid hormone.
(2) Glycoprotein hormones – protein
hormones with carbohydrate groups attached to the amino acid chain.
(3) Peptide hormones – smaller
than protein hormones; short chain of amino acids; e.g. oxytocin and
antidiuretic hormone (ADH)
(4) Amino acid derivative hormones – each is
derived from a single amino acid molecule.
(a) Amine hormones – synthesized
by modifying a single molecule of tyrosine; produced by neurosecretory cells
and by neurons; e.g. epinephrine and norepinephrine
(b) Amino acid
derivatives
produced by the thyroid gland; synthesized by adding iodine to tyrosine.
Mechanism of
action
(1) Non–steroid
hormones and growth factors cannot cross the plasma membrane and enter the
cell. Therefore, their receptors must be located on the extracellular side of
the plasma membrane so that the hormone can bind to it. An exception to this is
the thyroid hormone.
(2) A non–steroid
hormone molecule acts as a “first messenger” and delivers its
chemical message to fixed receptors in the target cell’s plasma membrane.
(3) The “message”
is then passed into the cell where a “second messenger” triggers
the appropriate cellular changes.
(4) Second
messenger mechanism (cyclic adenosine monophosphate / cAMP or inositol
triphosphate)
– produces target cell effects that differ from steroid hormone effects in
several important ways:
(a) The effects of
the hormone are amplified by the cascade of reactions.
(b) Second
messenger mechanism operates much more quickly than the steroid mechanism.
(5) The nuclear
receptor mechanism – small iodinated amino acids (T4 and T3)
enter the target cell and bind to receptors associated with a DNA molecule in
the nucleus; this binding triggers transcription of mRNA and synthesis of new
enzymes.
3. According to tissue origin
a. Pituitary gland hormones
Three types of
cells can identified base on staining reaction (Anterior pituitary)
(1) Chromophobes – make up
approximately one half of all cells in adenohypophysis.
(2) Acidophils – make up
approximately 40% of all cells of adenohypophysis; secrete GH and PRL.
(3)Basophils – form about
10% of adenohypophysis; secrete TSH, ACTH, FSH, LH and MSH
Posterior
pituitary
(1) Antidiuretic
hormone
(2) Oxytocin
b. Pineal gland – secrete melatonin
c. Thyroid gland
(1)
Tetraiodothyronine (T4)
(2)
Triiodothyronine (T3)
(3)
Calcitonin
d. Parathyroid gland – secretes
parathyroid hormone (PTH)
e. Adrenal gland
Adrenal cortex
(1) Aldosterone
(2) Cortisol
(3) Corticosterone
(4) Cortisone
Adrenal
medulla
(1) Epinephrine
(80%)
(2) Norepinephrine
(20%)
f. Pancreatic islet
(1)
Alpha cells (A cells) – secrete
glucagon
(2)
Beta cells (B cells) – secrete
insulin; accounts for up to 75% of all pancreatic islet cells
(3)
Delta cells (D cells) – secrete
somatostatin
g. Gonads
(1) Testes
(a) Testosterone
(b) Androgen
(2) Ovary
(a) Estrogen
(b) Progesterone
h. Thymus – secrete thymosin
Specimen collection for
hormonal studies:
1. Patient need
not to fast prior to collection of blood specimen
2. Serum is the
specimen of choice for hormonal studies.
3. Clot should be
immediately separated from serum after collection
4. Serum samples
are stable at –20oC for several weeks
5. The time of
collection as well as the position of the patient during collection should
always be noted.
6. Non–hemolyze,
non–icteric and non–lipemic sample is preferred for hormonal studies.
7. Repeated
freezing and thawing should be avoided.
Methods of quantitating
hormones:
1. Radioimmunoassay
2. Competitive
binding assay
3. IRMA
No comments:
Post a Comment