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GENERAL CONCEPT OF

HORMONE
SITI ANNISA DEVI TRUSDA
OVERVIEW
• DEFINITION
• CLASSIFICATION
• REGULATION OF SECRETION
• TRANSPORT to target cells
• RECEPTORS
• HORMONE MEASUREMENTS
Definition of Hormones

 A hormone is a chemical signal that is


secreted into the circulatory system and
communicates regulatory messages
within the body.
 Hormones may reach all parts of the
body, but only certain types of cells,
target cells, are equipped to respond.
Systems of Internal Communication

 Human has two systems of internal


communication and regulation:
 The nervous system
 The endocrine system
Systems of Internal Communication

 The nervous system conveys high-


speed electrical signals along
specialized cells called neurons.
 The endocrine system, made up of
endocrine glands, secretes hormones
that coordinate slower but longer-acting
responses to stimuli.
Hormones

 Advantages of using chemical


messengers:
 Chemical molecules can spread to all
tissues through the blood.
 Chemical signals can persist longer than
electrical ones.
 Many different kinds of chemicals can act as
hormones; different hormones can target
different tissues.
Levels at which hormones actions are considered
WHOLE BODY LEVEL
Regulation and integration of:
 Ionic and fluid balance
 Energy balance (metabolism)
 Coping with the environment
 Growth and development
 Reproduction

HORMONE ACTIONS

MOLECULAR LEVEL CELLULAR LEVEL


Regulation of: Regulation of:
 Gene transcription  Cell division
 Protein synthesis and degradation  Differentiation
 Enzyme activity  Death (apoptosis)
 Protein conformation and protein :  Motility
protein interactions  Secretion
 Nutrient uptake
Endocrine Organs
 Purely endocrine organs
 Pituitary gland
 Pineal gland
 Thyroid gland
 Parathyroid glands
 Adrenal: 2 glands
 Cortex
 Medulla
 Endocrine cells in other
organs
 Pancreas
 Thymus
 Gonads
 Hypothalamus
8
Glands

 Many hormones are secreted by


ductless endocrine glands.
 Obtain raw materials from and secrete
hormones directly into the bloodstream.
 Exocrine glands have ducts for
discharging secretions onto a free
surface.
 Sweat glands, salivary glands, enzyme-
secreting glands in the digestive tract.
• Paracrine: hormones act on neighboring non-hormone-
producing cells, e.g: sex steroids in the ovary,
angiotensin II in the kidney, PDGF in the vascular wall.
• Juxtacrine: peptide hormones can remaining in the
membrane of one cell and interact with a receptor on a
juxtaposed cell, e.g: hematopoietic growth factors
• Autocrine: hormone is released and acts on receptor
located on the same cell, e.g: important in promoting
unregulated growth of cancer cells.
• Intracrine: Hormones can also act inside the cell
without being released, e.g: insulin can inhibit its own
release from pancreatic islet β cells and somatostatin
can inhibit its own release from pancreatic D cells.
CLASSIFICATION OF HORMONES
The classical hormones fall into three categories:
• Derivatives of the amino acid tyrosine.
• Steroids hormones and Vitamin D, which are
derivatives of cholesterol.
• Peptides/proteins, which comprise the largest
and most diverse class of hormones.
HORMONE CLASSIFICATION
Hormones are classified according to :
• The distance or the routes by which the
hormone acts : autocrine, paracrine,
endocrine, and neurocrine
• Solubility : lipophilic, hydrophilic
• Chemical composition :
– polypeptide derivatives
– steroid derivatives
– amino acid derivatives
• Location of receptors :
– surface / membrane receptors : polypeptide H,
epinephrine
– intracellular receptors(cytosolic /nucleic): steroid
H, thyroid H
• Nature of mediator ( second messenger) :
– intracellular receptor
• ligand – receptor complex
– surface receptor
• c- AMP, c – GMP - Ca2+, inositol triphosphat ( IP3)
• protein – kinase : tyrosine – kinase  kinase cascade
Control Pathways and Feedback
Loops
 A common feature of
control pathways is a
feedback loop
connecting the
response to the
initial stimulus.
 Negative feedback
regulates many
hormonal pathways
involved in
homeostasis.
RECEPTORS
Membrane-Bound Receptors
 Many hormones are too
large, or too polar, to
pass through plasma
membranes.
 Bind to transmembrane
proteins that act as
receptor sites on target
cell membranes.
 Hormone is first
messenger.
 Causes activation of a
second messenger
in the cytoplasm.
 cAMP
Nuclear Receptors
 Steroid hormones are
lipid soluble molecules
that bind to hormone
receptors in the
cytoplasm of the target
cell.
 Site of activity is the
nucleus.
 Steroids are
manufactured from
cholesterol.
 Estrogen, progesterone,
testosterone, cortisol.
Nuclear Receptors

 Thyroid hormones
and insect-molting
hormone (ecdysone)
also act through
nuclear receptors.
 Binds to
transmembrane
protein that uses
ATP to move it into
the cell.
Lipophilic hormone → intracellular receptor :
cytoplasmic rec.: glucocorticoid, mineralocorticoid
nucleic rec. : thyroid H, estrogen, vit.D progesterone,
androgen
Hydrophilic hormone → membrane receptor (3 types) :
type I : enzyme (tyrosine kinase) activity (insulin, growth
factors)
type II : ion channels Na+, K+, Cl- (neurotransmitters)
type III: via G-proteins
Depend on the type of G-protein :
1. α- subunit of G-protein - activates adenylate cyclase (Gs)
producing c-AMP →
intracellular c-AMP ↑
inhibits adenylate cyclase (Gi) → intracellular c-AMP↓
2. α- subunit of G-protein stimulates c-GMP phosphodiesterase → c-
GMP ↓
3. α- subunit of G-protein binds to ion channel (K+ / Ca2+ channel)
→ opening of the channel
4. α- subunit of G-protein activates phospholipase C which then
hydrolyzes phosphatidyl inositol biphosphat (PIP2) producing
inositol triphosphat (IP3) + diacylglycerol (DAG)IP3 moves to
endoplasmic reticulum, stimulates release of Ca2+ from the
stores. DAG activates protein kinase C, which will phosphorylates
proteins, altering its activities
TRANSPORT OF HORMONES IN BLOOD
• Protein hormones water-soluble and readily
transported by the circulatory system.
• Steroid and thyroid insoluble in water
need carrierTBG, sex hormone–binding
globulin (SHBG), and corticosteroid-binding
globulin (CBG),as well as to albumin.
REGULATION OF SECRETION
CNS


+ Precursors
+ R
+
Hypothalamus

Liberin + H H Statin 
+ 
Precursors
+ 
Pituitary +  R

Tropin Negative
H feed-
back

Peripheral Precursors
+
gland +

Glandular
hormone

Target
cell
Response
External stimuli

Neuroendocrine Central nervous system


origin of
signals Hypothalamus

Hypothalamic hormones
(releasing factors)

First targets Anterior pituitary Posterior pituitary

Corticotropin Thyrotropin Follicle- Luteinizing Somatotropin Prolactin Oxytocin Vasopressin Blood


(ACTH) Mr28,000 stimulating hormone (growth Mr22,000 Mr1,007 (antidiuretic glucose
Mr4,500 hormone Mr20,500 hormone) hormone) level
Mr24,000 Mr21,500 Mr1,040

Second Adrenal Thyroid Ovaries/testes Islet cells of Adrenal


targets cortex pancreas medulla

Cortisol Thyroxine Progesterone, Testosteron


corticosterone, (T4), triiodo Insulin, Epinephrin
estradiol e glucagon,
aldosterone thyronine e
somatostatin
(T3)

Ultimate Many Muscles, Reproductive Liver, Mammary Smooth Arteriole Liver, Liver,
targets tissues liver organs bone glands muscle, s muscles muscles,
mammary heart
glands
General features of signal

Group I Group II
Steroids, iodothyronines, Polipeptides, proteins,
Type
calcitriol, retinoids glycoproteins, catecholamines
Solubility Lipophilic Hydrophilic
Transport proteins Yes No
Plasma half life Long (hours to days) Short (minutes)
Receptor Intracellular Plasma membrane
cAMP, cGMP, Ca2+, DAG, IP3,
Mediator Receptor-hormone complex
kinase-cascades
HORMONE MEASUREMENT
Endocrine function can be assessed by
• measuring levels of basal circulating hormone,
• evoked or suppressed hormone
• evoked or suppressed hormone-binding proteins.
• Alternatively, peripheral hormone receptor function can be assessed
Condition of measurement
• Fasting: thyroid hormone, prolactin, and IGF-I levels can be accurately
assessed in fasting morning serum samples.
• when hormone secretion is clearly episodic, timed samples may be
required over a defined time course to reflect hormone bioavailability.
• early morning and late evening cortisol measurements are most
appropriate. Although 24-hour sampling for GH measurements,with
samples collected every 2,10, or 20 minutes, are expensive and
cumbersome, they may yield valuable diagnostic information. Random
sampling may also reflect secretion peaks or nadirs, thus confounding
adequate interpretation of results.
• In general, confirmation of failed glandular function is
made by attempting to evoke hormone secretion by
recognized stimuli.
• Injection of trophic hormones, including TSH and
ACTH, evokes specific target gland hormone secretion.
Pharmacologic stimuli, for example metoclopromide
for induction of prolactin secretion,may also be useful
tests of hormone reserve.
• In contrast, hormone hypersecretion can be diagnosed
by suppressing glandular function. Thus, failure to
appropriately suppress GH levels after a standardized
glucose load implies inappropriate GH hypersecretion.
• Radioimmunoassays utilize highly specific
antibodies unique to the hormone,or a hormone
fragment, to quantify hormone levels.
• Enzyme-linked immunoabsorbent assays (ELISA)
employ enzymes instead of radioactive hormone
markers, and enzyme activity is reflective of
hormone concentration.
• This sensitive technique has allowed
ultrasensitive measurements of physiologic
hormone concentrations. Hormone-specific
receptors may be employed in place of the
antibody in a radioreceptor assay.
ENDOCRINE DISEASES
Endocrine diseases fall into four broad
categories:
(1) hormone overproduction
(2) hormone underproduction
(3) altered tissue responses to hormones; and
(4) tumors of endocrine glands.

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