Post on 13-Nov-2014
Dr. Yaser AshourDr. Yaser Ashour
THE
ENDOCRINE
SYSTEM
Dr. Yaser AshourDr. Yaser Ashour
THE ENDOCRINE SYSTEMBy
Dr. Yaser Mohamed Ashour
Prof. of Physiology Al Azhar Faculty of Medicine (Assuit)
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IntroductionIntroduction• The body functions are regulated by nervous
and endocrine systems aiming for homeostasis.• Both systems represent two parts of continuum
of control systems.• The difference between the two systems is in
their speed and time needed to exert their action.
• The nervous system responds within a fraction of seconds whereas the endocrine system
responds from a fraction of second up to over cycles of days, month or even years.
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• The difference in time factor because the nervous system depends upon an action potential as a conductor of its signal, which travel along the nerve
fibers within a fraction of seconds while the endocrine system depends
upon a chemical substance called hormone which travel allover the body with blood to exert the signal which it
carries.
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• Both systems are integrated to control homeostasis and
this principle is clearly seen in the hypothalamus and
pituitary gland where the two systems are linked
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• (1) The nervous system mediate its activity through
nerves that directly innervate the cells being controlled, by releasing
regulatory molecules known as
neurotransmitters to achieve the desired effect
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• (2) Both systems enable the body to respond to a wide range of internal and external stimuli by electing appropriate
responses to these stimuli that ensure that the physiological functioning of the
body is done to achieve homeostasis.
HOMEOSTASISkeeping the parameters of the body
in a steady, same state.
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The endocrine system consists of glands, The endocrine system consists of glands, which secrete hormones directly into blood which secrete hormones directly into blood
stream.stream. Major Endocrine Glands Major Endocrine Glands
• Hypothalamus• Anterior pituitary• Posterior pituitary• Pineal• Thyroid• Parathyroids
• Adrenal medulla• Adrenal cortex• Pancreas• Ovaries• Testes• Placenta
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THE HORMONESTHE HORMONES
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• The endocrine gland secrete a chemical substance called hormone
• Hormone is a chemical transmitter (messenger) synthesized by specialized
cells (glandular cells) and carried by bloodstream after its secretion in
response to a specific stimulus to exert its physiological control on other
distant target cells.
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Hormones are grouped into three classes:
• Steroids: These are derivatives of cholesterol e.g. testosterone,
estrogen, cortisol, and Aldosterone.
• Peptides: These are short chains of amino acids e.g. growth hormone,
insulin, and ADH.
• Amines: These are formed of amino acid as T3 – T4 and adrenaline.
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Properties of HormonesProperties of Hormones
1- Hormones are synthesized continuously.
2- Hormones may be stored within the cytoplasm of the cells as inactive granule e.g. pituitary
hormones or in the form of colloid mass as in thyroid acini.
3- Some hormones are secreted by more than one gland e.g. estrogenic hormones are secreted by
(ovary, placenta and adrenal cortex).
4 -Most hormones are released from their glands in short burst (pulses) that maintain basal definite
level for each hormone in blood.
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5- The hormone secretion show diurnal variation (circadian rhythm) e.g. growth hormone secretion is markedly increased in early
hours of sleep, while plasma cortisol rise in early morning.
6- Reciprocal chemical regulation: The stimuli which produce secretion of one hormone
inhibits the release of its antagonistic e.g. fall in plasma calcium stimulate secretion of
parathormone and inhibit the secretion of thyrocalcitonin hormone.
7- Hormones produce their physiological effect by a very low concentration in blood.
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8- Hormones act on a very specific receptors.
9- Hormones act as trigger substances, which initiate biochemical reactions that persist after disappearance of hormone
from blood.
10- Hormones may affect many cells of the body e.g. insulin & thyroxine.
11- Hormones may produce specific action e.g. insulin lowers blood glucose.
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12- Hormones can be classified into local and general hormones:-
- Local hormones which have specific local effects at or near their site of release e.g. G.I.T.
hormones.
- General hormones which have generalized effects away from its site of release e.g.
pituitary hormone.
13- Antigenic property: protein and peptide hormones stimulate the formation of
antihormone when injected to another species due to difference in the arrangement of amino
acids at parts of molecule.
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1. STEROID HORMONES (LIPID SOLUBLE)
-Pass through the cell membrane to a receptor in the nucleus .
-Activates genes that cause the production of new proteins.
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PEPTIDE (PROTEIN) HORMONESwater soluble
-Bind to cell membrane receptor.
-series of reactions that alter cell activity.
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The Mechanisms of Hormones ActionThe Mechanisms of Hormones Action
• The chemical nature of a hormone has implications for its transport in blood and its mechanism of
action at the target cell. The hormones are classified as fallow:-
• Hydrophilic hormones: (water soluble hormones), which include peptide
and adrenaline.• Lipophilic hormones:
(Lipid soluble hormones), which include the steroid and T3, T4.
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• The hormone action starts by binding of the hormone to the receptor, which they are located
either on the cell membrane, cytoplasm or nucleus of the cell.
• The binding of a hormone molecule with a specific receptor leads to the formation of a
receptor hormone complex.• Receptors on target cell membranes bind only to
one type of hormone. • More than fifty human hormones have been
identified. • All act by binding to receptor molecules.
• The binding hormone changes the shape of the receptor causing the response to the hormone.
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The mechanism of hydrophilic hormone The mechanism of hydrophilic hormone action (water soluble).action (water soluble).
• Hydrophilic hormones bind to external receptors found in the cell membrane of the target cells.
• Binding of the hormone to the receptor activates the receptor which leads to one of the following reactions:-
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Cell surface receptorsCell surface receptors
• Peptide hormones and catecholamines bind to cell surface receptors
• Receptors have extracellular, transmembrane and intracellular domains
• Extracellular domain contains ligand (hormone) binding site
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Cell surface receptorsCell surface receptors
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G protein –linked receptorsG protein –linked receptors
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Non-G linked receptorsNon-G linked receptors
• Cell surface receptors with intracellular domains with intrinsic enzymatic activity– Protein kinase (serine or tyrosine kinases)
• Or intracellular domains that link closely to other enzymes
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Non-G protein ReceptorsNon-G protein Receptors
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Second messengersSecond messengers
• Binding to cell surface receptors releases second messenger molecules inside cell
• Second messengers include – cAMP or cGMP– phopholipids diacylglycerol and inositol triphosphate
(DAG and IP3) – calcium
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cAMP as second messenger cAMP as second messenger
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Phospholipids as Second MessengersPhospholipids as Second Messengers
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Biological effectsBiological effects
• Second messengers create phenotypic changes in target cells– Alter phosphorylation (activity) of proteins– Alter permeability of membranes– Indirectly influence gene expression
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Receptor Down-regulationReceptor Down-regulation
• After hormone binding receptors may be internalized (coated pits)
• Leads to reduced responsiveness of target cell (usually temporary)
• Receptor may be recycled to cell surface or degraded
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Intracellular ReceptorsIntracellular Receptors• Steroid and thyroid hormones act via
intracellular receptors• Hormone-receptor complex interacts
directly with DNA in chromatin fiber at the promoter of specific genes
• H-R complex acts as a transcription factor to enhance (or decrease) rate of transcription
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Intracellular ReceptorsIntracellular Receptors
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Steroid Receptor DomainsSteroid Receptor Domains
Steroid receptors interact with the grooves in DNA double-helix via ‘zinc fingers’ formed as loops in the receptor
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Response Elements in GenesResponse Elements in Genes• Steroid hormone receptors recognize specific
DNA elements in genes • Short elements are steroid specific
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Endocrine DysfunctionEndocrine Dysfunction
• At level of endocrine gland– Structure, secretion,
stability, elimination of hormone
– Primary problems in gland of origin
– Secondary due to signals from Hypo-Pit
– Presence of other agonists / antagonists
• At level of target cell– Structure, stability of
receptor– Downregulation
reduces sensitivity– Post-receptor signal
transduction defects• Second messengers• Gene expression• HRE
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Regulation of endocrine systemRegulation of endocrine systemDirect negative feedback:
• There is direct interaction between the controlling hormone and the controlled
metabolite: - e.g.:- Plasma calcium level.
• E.g. In case of decreased plasma calcium level this is detected directly by
parathyroid cells lead to synthesis of parathormone hormone leads to increase
calcium level by increased secretion.
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Indirect negative Feedback:• Some peripheral endocrine glands (thyroid,
adrenal cortex and gonads) are dependent on the regulation provided by hormones released from the anterior pituitary, whose release is in
turn dependent on the endocrine activity of hypothalamus.
• In this situation, the hypothalamic neuroendocrine cells are frequently integrating information from a variety of sources, including
the circulating levels of the hormone secreted by the peripheral endocrine gland.
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Negative Feedback:
A self-correcting system
normal
Upper limit
Lower limit
Blglu
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A Negative Feedback System
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Positive Feedback:Positive Feedback:• Positive feedback exists when a hormone is able
to stimulate its own production.
• Such situations are rare and the only example that is well documented, relates to ovulation and 17 b-oestrdiol, which achieves positive feedback by stimulating the release of hypothalamic GnRH; this causes the release of pituitary FSH and LH, which in turn stimulates the production of more 17 b-oestradiol by the ovary.
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Positive Feedback?
This is a NON-correcting system. A little becomes more. Less becomes a lot less.
Examples: Oxytocin and Prolactin hormones
.
Hypothalamus and Hypothalamus and PituitaryPituitary
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Hypothalamus and PituitaryHypothalamus and Pituitary
• The hypothalamus-pituitary unit is the most dominant portion of the entire endocrine system.
• The output of the hypothalamus-pituitary unit regulates the function of the thyroid, adrenal and reproductive glands and also controls somatic growth, lactation, milk secretion and water metabolism.
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Hypothalamus and pituitaryHypothalamus and pituitary glandgland
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Hypothalamus and pituitaryHypothalamus and pituitary glandgland
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• Pituitary function depends on the hypothalamus and the anatomical organization of the hypothalamus-pituitary unit reflects this relationship.
• The pituitary gland lies in a pocket of bone at the base of the brain, just below the hypothalamus to which it is connected by a stalk containing nerve fibers and blood vessels. The pituitary is composed to two lobes-- anterior and posterior
Hypothalamus and PituitaryHypothalamus and Pituitary
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Posterior Pituitary: Posterior Pituitary: neurohypophysisneurohypophysis
• Posterior pituitary: an outgrowth of the hypothalamus composed of neural tissue.
• Hypothalamic neurons pass through the neural stalk and end in the posterior pituitary.
• The upper portion of the neural stalk extends into the hypothalamus and is called the median eminence.
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Hypothalamus and Hypothalamus and posterior pituitaryposterior pituitary
Midsagital view illustrates that magnocellular neurons paraventricular and supraoptic nuclei secrete oxytocin and vasopressin directly into capillaries in the posterior lobe
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ADH = ANTIDIURETIC HORMONEADH = ANTIDIURETIC HORMONE
1. low water concentration of blood (causes of dehydration?)
2. hypothalamus osmoreceptors fire
3. posterior pituitary secretes ADH and increases thirst.
4. ADH - increases permeability of kidney tubules to water, increasing reabsorption of water from urine into blood.. (stealing water from the urine)
5. High water concentration of blood
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-DIURETICS (caffeine, alcohol) interfere with ADH, so water remains in urine and is not returned to blood. Results in dehydration.
-DIABETES INSIPIDUS –very little ADH is made, so water is not reabsorbed from urine.
Symptoms: excessive urination (12L) thirst, copious dilute urine.
-Bedwetting: due to low ADH? Nosespray?
-What medical conditions could be treated with diuretics?
-Why are athletes advised against cola and coffee?
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Anterior pituitary: Anterior pituitary: adenohypophysisadenohypophysis
• Anterior pituitary: connected to the hypothalamus by the superior hypophyseal artery.
• The antererior pituitary is an amalgam of hormone producing glandular cells.
• The anterior pituitary produces six peptide hormones: prolactin, growth hormone (GH), thyroid stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH).
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Hypothalamus and Hypothalamus and anterior pituitaryanterior pituitary
Midsagital view illustrates parvicellular neurosecretory cells secrete releasing factors into capillaries of the pituitary portal system at the median eminence which are then transported to the anterior pituitary gland to regulate the secretion of pituitary hormones.
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Reituclar activating substance
Thalamus
neocortex
Limbic system
Optical system
Heat regulation (temperature)
Energy regulation (hunger,
BMI)
Autonomic regulation
(blood pressure etc)
Water balance (blood volume, intake--thirst, output—urine volume)
Metabolic rate, stress response, growth,
reproduction, lactation)
Sleep/wake
pain Emotion, fright, rage, smell vision
Anterior pituitary
hormonesposterior pituitary
hormones
Regulation Regulation of of
HypothalamusHypothalamus
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Hypothalamus/Pituitary Hypothalamus/Pituitary AxisAxis
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Hypothalamic releasing factors for Hypothalamic releasing factors for anterior pituitary hormonesanterior pituitary hormones
Travel to adenohypophysis via hypophyseal-portal circulation
Travel to specific cells in anterior pituitary to stimulate synthesis and secretion of trophic hormones
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Hypothalamic releasing hormonesHypothalamic releasing hormones
Hypothalamic releasing hormone Effect on pituitary
Corticotropin releasing hormone (CRH)
Stimulates ACTH secretion
Thyrotropin releasing hormone (TRH)
Stimulates TSH and Prolactin secretion
Growth hormone releasing hormone (GHRH)
Stimulates GH secretion
Somatostatin Inhibits GH (and other hormone) secretion
Gonadotropin releasing hormone (GnRH) a.k.a LHRH
Stimulates LH and FSH secretion
Prolactin releasing hormone (PRH) Stimulates PRL secretion
Prolactin inhibiting hormone (dopamine)
Inhibits PRL secretion
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Characteristics of hypothalamic Characteristics of hypothalamic releasing hormonesreleasing hormones
• Secretion in pulses• Act on specific membrane receptors• Transduce signals via second messengers• Stimulate release of stored pituitary hormones• Stimulate synthesis of pituitary hormones• Stimulates hyperplasia and hypertophy of target
cells• Regulates its own receptor
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Hypothalamus Hypothalamus and anterior and anterior
pituitarypituitary
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Anterior pituitaryAnterior pituitary
• Anterior pituitary: connected to the hypothalamus by hypothalmoanterior pituitary portal vessels.
• The anterior pituitary produces six peptide hormones: – Prolactin.– Growth hormone (GH), – thyroid stimulating hormone (TSH), – adrenocorticotropic hormone (ACTH), – follicle-stimulating hormone (FSH), – luteinizing hormone (LH).
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Anterior pituitary cells and hormonesAnterior pituitary cells and hormones
Cell type Pituitary population
Product Target
Corticotroph 15-20% ACTH-lipotropin
Adrenal glandAdipocytesMelanocytes
Thyrotroph 3-5% TSH Thyroid gland
Gonadotroph 10-15% LH, FSH Gonads
Somatotroph 40-50% GH All tissues, liver
Lactotroph 10-15% PRLBreastsgonads
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Anterior pituitary hormonesAnterior pituitary hormones
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THYROXINTHYROXIN
-Produced by the thyroid gland
-increases rate of metabolism (cell respiration)
-provides more energy, uses up glucose and oxygen, produces heat.
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Control of Control of thyroxin thyroxin secretionsecretion
1. low metabolic rate-
2. hypothalamus secretes TSHR
3. ant. Pit secretes TSH
4. thyroid secretes thyroxine
5. increase in metabolic rate
6. too high metabolic rate
7. hypoth. decreases TSHRF
8. ant pit decreases TSH
9. thyroid gland decreases thyroxine
10. metabolic rate decreases
TSHRF – Thyroid stimulating hormone releasing factor
TSH – Thyroid stimulating hormone
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hypothyroidismhypothyroidism – – low thyroxinelow thyroxine
-Symptoms: fatigue, weight gain in adults, cold, slow thought, possible goiter.
-called Cretinism in kids. Retarded and small.
Goiter: Results from low dietary Iodine.
Thyroid needs lots of Iodine to make thyroxine. With no iodine, high TSHRF and TSH continue to stimulate thyroid making it large and over-worked.
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Hyperthyroidism = high thyroxin
Exophthalmos due to hyperthyroidism
Symptoms:
High energy, weight loss, hunger,
very alert and unable to sleep.
Exophthalmos
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THE PARATHYROID GLANDSTHE PARATHYROID GLANDSANDAND
CALCIUM HOMEOSTASISCALCIUM HOMEOSTASIS
Plasma calcium levels are maintained within very narrow limits in order to support the many physiological
functions in which calcium is involved:• Calcium ions play an essential role in the regulation of
membrane permeability, and hence influence neuromuscular excitability.
• They participate in the release of neurotransmitters, and are a vital component in the excitation –
contraction process in muscle cells.
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• They are also involved in many intracellular metabolic pathways where they act as coenzymes and
regulators, and in both endocrine and exocrine cells they are often implicated in excitation-secretions
pathways.• Blood coagulation is dependent on normal levels of
calcium, as are bone & teeth formation and milk production.
• More than 99% of total body calcium is contained in bone and, although it provides the principle store of calcium most is incorporated into a complex crystal structure called hydroxyapatite, which means that it
cannot be released quickly when required.
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• The remaining 1% of the calcium in bone can be readily exchanged, being in the form of
calcium phosphate salts that are in equilibrium with plasma calcium and hence provide a
convenient buffer to sudden changes in calcium levels.
• Normally, plasma calcium is maintained at 2.3-2.6 m mol/L and is present in three forms:-
• Diffusible ionized= ionic Ca++= 50%= 1.2 m mol/L* non diffusible= protein bound= 41%= 1.0
m mol/LDiffusible= combined with citrate/phosphate= 9%= 0.2 m mol/LTotal= 2.4
m mol/L
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• The daily loss of calcium from the body in nails, dead cells and hair, is added to daily flux of calcium across
the gastrointestinal and kidney epithelia.
• The net result is daily loss of 1000 mg of calcium which needs to be
replaced in the diet.
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Regulation of plasma calcium Regulation of plasma calcium depends upon:-depends upon:-
• Parathormone (PTH) plasma Ca++ level. • Calcitonin plasma Ca++ level.• 1, 25 dihydrocholecalciferol plasma Ca++
level.• Adrenal glucocorticoids plasma Ca++
level act as anti vitamin D.• Growth hormone plasma Ca++ level by
Ca++ excretion & Ca++ absorption.• Thyroid hormone plasma Ca++ level.
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Parathormone Hormone:Parathormone Hormone:• This hormone is secreted by the parathyroid
glands. • The parathyroid glands are four, and they are
embedded in the posterior surface of thyroid gland. Two in each lobe.
• There are two cells in the parathyroid gland:• Chief cells producing parathormone
hormone.• Oxyphilic cells whose function is not yet
clear.
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Action of the parathormone:Action of the parathormone:• The parathormone is a major regulating
factor for both calcium (Ca++) and phosphate (PO4--) concentrations in body fluids.
• Normally, the plasma PO4—concentration is inversely related to the Ca++ concentration Ca++ 1/a PO4--.
• Ca++ X PO4 = constant = solubility product.
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• The main function of PTH is to increase the plasma Ca++ level and
decrease the plasma PO4-- level.
• A reciprocal relationship exists between plasma calcium and
phosphate, such that a decrease in one results in an elevation of the
other, and vice versa.
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PTH exerts its actions by working on (kidney, bone & intestine).PTH exerts its actions by working on (kidney, bone & intestine).
Kidney:• More than 95% of the filtered calcium load is reabsorbed via a number of active and passive
transport mechanisms.• PTH: inhibits reabsorption of calcium in the
proximal tubule & stimulate reabsorption in the distal nephron there is overall effect of
increased reabsorption and increased plasma calcium concentration.
• PTH inhibit phosphate reabsorption by the proximal convoluted tubules this lead to:-
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Phosphate excretion in urine. Phosphate level in plasma.
Calcium level in plasma to maintain the solubility product constant i.e. Ca++ X PO-- =
constant.
• PTH activates renal 1-hydroxylase which converts 25-hydroxycholecalciferol to active 1,
25 dihydroxycholecalciferol.
• PTH increase Mg++ and H+ reabsorption by renal tubules.
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Gastrointestinal tract (intestine):Gastrointestinal tract (intestine):
• PTH has no direct effect on the intestine.
• PTH has an indirect effect on the intestine through its stimulation of kidney to form 1,
25 dihydroxycholecalciferol which in turn stimulate Ca++ & PO4-- absorption from
upper small intestine.
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Bone:Bone:• 99% of the body’s calcium is in bone, and 99% of
this calcium is contained in a complex mineralized matrix of hydroxyapatite crystals from which calcium
ions cannot readily be removed.• However, a small proportion of bone is constantly
remodeled throughout life, which is why bones are able to heal following a fracture.
• This remodeling is a dynamic equilibrium in which bone resorption roughly equals bone formation.
• PTH is able to influence the buffering capability provided by the calcium phosphate salts present in
this readily exchangeable bone.
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Control of parathormone secretion: Control of parathormone secretion: PTH is regulated by:-PTH is regulated by:-
(1) Ca++ ions level in plasma: Ca++ level by 0.5 mg % stimulate PTH
secretion. Ca++ level inhibit PTH secretion.
(2) PO4-- Level in plasma: PO4—plasma level stimulates PTH secretion.
(3) Mg++ level in plasma: Mg++ level stimulate PTH secretion.
Mg++ level inhibit PTH secretion.
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Calcitonin:Calcitonin:
• Calcitonin (CT) is a calcium lowering hormone.
• It is a polypeptide secreted from the Parafollicular cells of the thyroid gland.
• It was found that (CT) also found in the brain, pituitary, thymus, lung, liver and gut.
• The plasma level of CT is 2-4 mg %.
• Its half life in circulation is less than 10 minutes.
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Actions of calcitonin:Actions of calcitonin:(1) Effect on Bone:• Inhibits bone resorption by:• Inhibit the permeability of osteoclasts and osteocytes
to calcium i.e. decrease mobilization of calcium from both.
The activity and numbers of osteoclast.(2) Effect on G.I.I.:• Inhibit intestinal absorption of Ca++ & PO4--. Gastric acid secretion.(3) Effect on kidney: Urinary excretion of PO4--, Ca++ and Na+, Cl-.• Inhibit renal 1 a-hydroxylase activity.
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Vitamin DVitamin D• Vitamin D It is word refer to a group of a
closely related sterols, the commonest of which are vitamin D2 (calciferol) and vitamin D3
(cholecalciferol).
• Vitamin D3: is formed in the skin by the effect of ultraviolet rays of the sun, also it is taken in the
diet (e.g. cod liver oil and egg yolk).
• Vitamin D2: is taken in food and it has the metabolism as VD3.
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Action of VitaminAction of Vitamin D3:D3:It increases absorption of both Ca++ &
PO4—from intestine.
It mobilizes both Ca++ & PO4—from bone.
It facilitates Ca++ reabsorption in the kidneys.
It helps development of normal bone and teeth.
It stimulates differentiation of immune cells and keratinocytes in the skin.
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Other hormones affecting calcium metabolism:
• Glucocorticoids Ca++ level.
• Growth hormone Ca++ level.
• Thyroxine hypercalcaemia – hypercalciuria & osteoprosis.
• Sex hormones Androgen * calcium retention
• Oestrogen * plasma Ca++ level.
* prevent osteoprosis.
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Control of Ca++ blood Control of Ca++ blood concentration is by concentration is by PTH PTH
and Calcitonin.and Calcitonin.
-Calcium can move between the blood and the storage pools in bones and
teeth depending on the body’s needs.
……..What is calcium needed for?
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PARATHYROID HORMONEPARATHYROID HORMONE
-Produced by parathyroid glands when blood calcium is low.
PTH increases blood calcium by
1. Dissolving Ca from bones and teeth into blood.
2. Causing increased absorption of Ca from the gut into the blood
When would you expect PTH blood concentrations to be high?
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OSTEOPOROSIS is Calcium loss from bone.
If your diet and thus your blood is low in calcium then PTH will be dissolving your bones resulting in osteoporosis. Low estrogen in menopause makes it even worse.
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CALCITONIN HORMONECALCITONIN HORMONE Produced by thyroid gland when
blood Ca levels are high.
Calcitonin decreases blood Ca by:
1. Increasing Ca deposition in bones and teeth.
2. Reducing Ca absorption from the gut into the blood.
When would you expect Calcitonin blood concentrations to be high?
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Where is calcitonin and PTH Where is calcitonin and PTH released?released?
Blood calcium
A
B
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Disorders of Calcium HomeostasisDisorders of Calcium Homeostasis
Hypovitaminosis D:
• Vitamin D deficiency causes Rickets in children and osteomalacia in adults.
Causes:
• Inadequate intake of vitamin D in diet.
• Inadequate exposure to ultraviolet rays.
• Inadequate absorption in the intestine e.g. celiac disease or obstructive jaundice.
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• Renal failure there is failure of hydroxylase 25 – hydroxycholcalciferol to calcitrol.
Manifestations:
• Lack of vit D decrease Ca++ absorption from the intestine hypocalcaemia
failure of mineralization of new bone and more secretion PTH lead to more bone
demineralization and mobilization of Ca++ from bone lead to Rickets in children and
osteomalacia in adult
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Rickets:
• This is a common disease in poor community due to malnutrition.
Characteristic of Rickets:
• Growth retardation or stoppage.
• Swelling near the joints (due to continuous growth of epiphyseal plates).
• Bone deformities:
* Bowing of leg.
* Pelvis deformity.
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Osteomalacia:
• This is a disease which occurs in adult due to hypocalcaemia and
usually it occurs in multipart ladies, and their bones become brittle, tender
and painful.
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Hypervitaminosis D:Prolonged administration of large doses of vitamin D
produce:-• Hypercalcaemia and deposition of calcium in soft
tissues. Calcium and phosphate excretion in urine polyuria
+ polydipsia.• Renal ischemia due to deposition of calcium in
renal blood vessel hypertension.• Renal failure due to calcium deposition in renal
tubules.• Other symptoms (anorexia, nausea, vomiting,
headache, drowsiness).• Bone resorption osteoporosis.
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Hyperparathyroidism:Hyperparathyroidism:• Hyperfunction of parathyroid gland is produced by parathyroid hyperplasia or adenoma with excess PTH
secretion.Manifestations:
* Urine & blood changes: Phosphate excretion in urine (hyperphosphaturia).
Plasma phosphate (hypophosphatatemia). Plasma calcium (Hypercalcaemia).
Calcium excretion in urine (hypercalciuria). Plasma alkaline phosphatase.
• * bone resorption decalcification of bones:• Bone becomes fragile bone show multiple cysts (ostitis
fibrosa cystica).
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Neuromuscular excitability (due to hypercalcaemia).
• Mental retardation.
• Depression of reflexes.
• Muscle weakness.
• Constipation.
• * Renal changes:
• Polyuria.
• Renal stones.
• Renal failure.
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HypoparathyroidismHypoparathyroidism
This is due to faulty removal of parathyroid during thyroidectomy.
Manifestations:• * Urine and blood changes: phosphate excretion in urine. phosphate level in plasma. calcium level in plasma. calcium excretion in urine.• * ionized Ca++ level in plasma:
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• Tetany. H.R., cardiac arrhythmia, prolongation of
S-T segment, and prolongation of Q-T interval.
• Intestinal and biliary colic.
• Opacity of eye lens (cataract).
• Hair falls & brittle nails.
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TETANY• It is a disease characterized by increased
neuromuscular excitability due to ionized calcium level in plasma.
• It is characterized by attacks of spasmodic contractions which may involve the laryngeal and
respiratory muscles.Causes of tetany:
• Hypocalcaemia: calcium level in blood due to:- - Hypoparathyroidism.
- calcium intake.- Calcium need (pregnancy & lactation).
- absorption of calcium as in:-- steatorrhea (fatty diarrhea) due to
combination of fat with calcium forming calcium soaps.
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• Deficiency of vitamin D. alkalinity of intestinal content which precipitates
calcium.• Administration of oxalate or citrate
• Oxalate precipitate calcium.• Citrate form unionized calcicitrate.
Types of Tetany• Upon the calcium level in the blood there are two
types of tetany:-1- Manifest tetany when the calcium level is below 7
mg %.2- Latent tetany when the calcium level drops
between 9 mg % 7 mg%.
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Manifest tetany:
Manifestations:
1- Fibrillary twitches of skeletal muscles and attacks of clonic & tonic contractions.
• These tonic contractions may lead to generalized convulsions.
• Spasmodic contraction of laryngeal muscles leads to respiratory distress and cyanosis.
• If this spasmodic contraction prolonged it leads to death as a result of asphyxia (laryngeal
stridor).
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2- Carpopedal spasm = obstetrician hand = Accoche’s hand.= carpal spasm = stiffness of
hand muscles.
There is flexion of wrist
Flexion of metacorpo-phalngeal joints.
Extension of interphalngeal joints.
Adduction of thumb into hand
Pedal spasm = dorsiflexion of foot toes are planter flexed.
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carpopedal spasmcarpopedal spasm
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Latent tetany:
• Plasma calcium level is above 7 mg % and 9 mg %.
• Manifestations of tetany are absent at rest.
• These manifestations appear when there is an increase of body need to calcium.
• Or there is exposure to stress e.g. pregnancy, lactation, emotion and
hyperventilation.
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Diagnosis of latent tetany:
1- Determination of ionized calcium level in plasma.
Trousseau’s sign: on application of occlusion of blood supply to the arm by sphygmomanometer
cuff Trousseau’s sign.
Chvostek’s sign: Tapping the facial nerve in front of the ear results in twitch of facial muscles especially the upper lip due to
increased excitability to mechanical stimuli.
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Erb’s sign: excitability of motor nerves to galvanic current.
• On application of a signal electric stimulus of any superficial motor nerve produce prolonged
spasmodic contraction in the supplied muscles in positive cases.
Treatment:* Acute tetanic attacks are treated by slow I.V. calcium
chloride injection.* After attack:
– * Vitamin D.– * Diet rich in calcium.
– * Ammonium chloride.– * PTH injection.* A.T.10
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GLUCAGONGLUCAGON
• Alpha cells secrete glucagon - peptide of 29 amino acids.– Stimulus for release is decrease in blood
glucose levels– Synthesized as a larger proglucagon
molecule and then clipped down by enzymes– Potent hyperglycemic agent - major target
organ is the liver– Stimulates glycogenolysis and lipolysis
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INSULININSULIN
• Beta cells secrete insulin - peptide of 51 amino acids.– Synthesized as a larger proinsulin molecule and
then clipped down by enzymes.– Lowers blood glucose by enhancing membrane
transport of glucose into body cells (especially muscle and fat cells). The brain, kidney and liver have easy access to glucose and do not require insulin.
– Inhibits glycogenolysis and gluconeogenesis
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INSULININSULIN
• After glucose enters a target cell, insulin binding triggers enzymatic activity that:– Catalyze the oxidation of glucose for ATP
production– Join glucose molecules together to form
glycogen – Convert excess glucose to fat
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INSULININSULIN• Diabetes mellitus results
from hyposecretion of insulin or hypoactivity of
insulin.• When insulin is absent or
deficient, blood sugar levels remain high after a meal because glucose is
unable to enter most tissue cells.
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DIABETESDIABETES
• Type I diabetes mellitus (insulin-dependent) afflicts 750, 000 Americans.
– Autoimmune disease (beta cells are attacked by immune cells). May be due to a virus
entering the body and mimicking beta cell antigens.
– Insulin is not produced or secreted, requiring regular insulin injections.
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DIABETESDIABETES
• Type II diabetes mellitis (non-insulin-dependent) afflicts 7.5 million
Americans.– Insulin resistance - Insulin is usually
produced but the receptors do not respond.
– The membrane protein PC-1 may be a culprit
– it has been shown to inhibit the tyrosine kinase receptor, but its mechanisms of action
are unknown.
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DIABETESDIABETESHeredity plays a role - an estimated 30% of
poples carry a gene that predisposes them to Type II diabetes.
Lifestyle play a role - Type II diabetics are almost always obese and sedentary.
Adipose tissue produces a hormone-like chemical called tumor necrosis factor-
alpha, which depresses synthesis the cellular glucose transporter (glut-4).
Cells cannot take up glucose in the absence of glut-4.
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ANTAGONISTIC HORMONE PAIRS
work together to keep a parameter from becoming too high or too low.
Eg. Insulin decreases blood glucose
Glucagon increases blood glucose
Eg. PTH increases blood Ca++
Calcitonin decreases blood Ca++
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Alpha islet cells secrete glucagon. Beta islet cells secrete insulin.
CONTROL OF BLOOD GLUCOSE - Where are insulin and glucagon secreted from? The islets of Langerhans in the pancreas.
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WHEN BL. GLUCOSE IS HIGH, INSULIN
DECREASES IT BY:
1. Increasing glucose permeability of cell
(open glucose gates on cell membranes).
2 Causes liver to remove excess glucose from the blood
and store it as liver glycogen and fat.
CELL
GLUCOSE
LIVER
GGGGGG
Dr. Yaser AshourDr. Yaser Ashour
INSULIN UNLOCKS THE GLUCOSE
GATES ON THE CELL SO GLUCOSE CAN ENTER THE CELL
FROM THE BLOODSTREAM.
If there is no insulin, glucose remains in the
blood (high bl. Glu) and the cell
starves, producing no energy. The victim becomes
tired and goes into a coma.
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WHEN GLUCOSE IS LOW, GLUCAGON WHEN GLUCOSE IS LOW, GLUCAGON INCREASES IT BY:INCREASES IT BY:
1. Decreasing permeability of cells to glucose (close glucose gates on cells).
2. Releasing stored glucose from the liver into the blood.
cell
liver
GGGGGGGGG
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When are insulin and When are insulin and glucagon released?glucagon released?
Blood
glucose
A
B
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What happens when insulin isn’t secreted What happens when insulin isn’t secreted or cells become insulin resistantor cells become insulin resistant? ?
Disease DIABETES MELLITUSDisease DIABETES MELLITUS
Type I: juvenile – due to lack of insulin
Type II: adult onset – due to insulin resistance (Associated with obesity).
Symptoms:
High blood glucose, fatigue, high glu in urine, high urine volume, weight loss.
Dr. Yaser AshourDr. Yaser Ashour
What’s the physiology behind these What’s the physiology behind these symptoms?symptoms?
High blood glucose
Fatigue
High glu in urine
High urine volume
Dry, itchy skin
Thirst
Weight loss.
Dr. Yaser AshourDr. Yaser Ashour
High blood glucose – glucose from food can not enter cells so it remains in blood.
Fatigue – cells lack glucose for cell respiration so no ATP energy is made.
High glu in urine – XS glu spills into urine and is not returned completely to blood by active transport.
High urine volume – Normally water from the urine follows glucose back into the blood by osmosis, but because some glu remains in the urine, the water remains with it.
Dry, itchy skin – The increased loss of water in urine dehydrates the blood stream.
Thirst – Same as above
Weight loss – The glucose lost in the urine is from your meals.
Dr. Yaser AshourDr. Yaser Ashour
Insulin
Pump automat-ically injects insulin into the blood
Continuous Blood Glucose monitoring .
Treatment Injection of insulin, oral hypoglycemic pills, control of exercise, diet, weight reduction.
Dr. Yaser AshourDr. Yaser Ashour
DIABETES DIABETES TECHNOLOGIESTECHNOLOGIES
Recombinant DNA technology: Human insulin gene transfered into bacteria?http://www.angelfire.com/dc/apgenetics/rec.dna.plasmid.gif
• Transplanting normal human islet cells into liver of diabetic patient? http://www.ianblumer.com/islet_cell_transplants.htm
Gene Therapy: Transplanting insulin genes into embryos or fetuses?
ASSIGNMENT: State the advantages and disadvantages of each technology.
Dr. Yaser AshourDr. Yaser Ashour
The
Edmonton
Protocol
Dr. Yaser AshourDr. Yaser Ashour
What happens if you can’t make What happens if you can’t make Glucagon ? Glucagon ? HYPOGLYCAEMIAHYPOGLYCAEMIA: :
Blood glucose can’t be raised- it stays low.
Symptoms:
· Low blood glucose, fatigue, passing out.
Treatment?
Dr. Yaser AshourDr. Yaser Ashour
HormonesHormones• Regulatory molecules
secreted into the blood or lymph by endocrine glands. “Ductless”– Lack ducts.– Derived from epithelium
but lose connection with surface.
• Carry hormone to target tissue where it produces its effects.
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Chemical Classification of Chemical Classification of HormonesHormones
• Amines
• Polypeptides
• Glycoproteins
• Steroids
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AminesAmines
• Hormones derived from tyrosine and tryptophan.
• Include hormones secreted by adrenal medulla, thyroid, and pineal glands.
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PolypeptidesPolypeptides
• Chains of amino acids (< 100 amino acids in length).– ADH
– Insulin
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GlycoproteinsGlycoproteins
• Long polypeptides (>100) bound to one or more carbohydrate (CHO) groups.– FSH
– LH
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SteroidsSteroids
• Lipids derived from cholesterol.
• Are lipophilic hormones.– Testosterone– Estradiol– Cortisol– Progesterone
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Thyroid HormonesThyroid Hormones
• Tyrosine derivatives bound together.
• Contain 4 iodine atoms (T4).
• Contain 3 iodine atoms (T3).
• Small, non-polar molecules.– Soluble in plasma
membranes.
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• Synergism:• Two hormones work together to produce a
result.– Additive:
• Each hormone separately produces response, together at same concentrations stimulate even greater effect.
– Epinephrine and norepinephrine.
– Complementary:• Each hormone stimulates different step in the process.
– FSH and testosterone.
Hormonal InteractionsHormonal Interactions
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Hormonal InteractionsHormonal Interactions
• Permissive effects:– Hormone enhances the responsiveness of
a target organ to second hormone.– Increases the activity of a second
hormone.• Prior exposure of uterus to estrogen induces
formation of receptors for progesterone.
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Hormonal InteractionsHormonal Interactions
• Antagonistic effects:
• Action of one hormone antagonizes the effects of another.
– Insulin and glucagon.
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Effects of Hormone Effects of Hormone ConcentrationConcentration
• Concentration of hormones in blood reflects the rate of secretion.
• Half-life: – Time required for the plasma concentration
is reduced to ½ reference level.
• Physiological range of concentration produces normal tissue response.
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Effects of Hormone Effects of Hormone ConcentrationConcentration
• Varying hormone concentration within normal, physiological range can affect the responsiveness of target cells.
• Priming effects (upregulation)– Increase number of receptors formed on
target cells.– Greater response by the target cell.
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Effects of Hormone Effects of Hormone ConcentrationConcentration
• Desensitization (downregulation):– Decrease in number of receptors on target
cells.– Produces less of a target cell response.
• Insulin in adipose cells.
• Pulsatile secretion may prevent downregulation.– GnRH and LH.
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Mechanisms of Hormone Mechanisms of Hormone ActionAction
• Hormones of same chemical class have similar mechanisms of action.– Location of cellular receptor proteins.
• Target cell must have specific receptors for that hormone (specificity).
• Hormones bind to receptors with high bond strength (affinity).
• Low capacity of receptors (saturation).
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Hormones That Bind to Hormones That Bind to Nuclear Receptor ProteinsNuclear Receptor Proteins
• Lipophilic steroid and thyroid hormones bound to plasma carrier proteins.
• Hormones dissociate from carrier proteins to pass through lipid component of the target cell membrane.
• Receptors for the lipophilic hormones are known as nuclear hormone receptors.
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Nuclear Hormone Nuclear Hormone ReceptorsReceptors
• Function within cell to activate genetic transcription.
• mRNA directs synthesis of specific enzyme proteins that change metabolism.
• Receptor must be activated by binding to hormone before binding to specific region of DNA called HRE (hormone responsive element).– Located adjacent to gene that will be transcribed.
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Mechanisms of Steroid Mechanisms of Steroid Hormone ActionHormone Action
• Steroid receptors located in cytoplasm.
• Bind to steroid hormone.
• Translocates to nucleus.
• DNA-binding domain binds to specific HRE of the DNA.
• Dimerization occurs.• Stimulates
transcription.
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Hormones That Use 2Hormones That Use 2ndnd MessengersMessengers
• Cannot pass through plasma membrane.• Catecholamines, polypeptides, and
glycoproteins bind to receptor proteins on the target cell membrane.
• Actions are mediated by 2nd messengers (signal-transduction mechanisms).– Extracellular hormones are transduced
into intracellular second messengers.
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Endocrine
Glands
Dr. Yaser AshourDr. Yaser AshourAnterior and posterior pituitary glands.
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• Also called the neurohypophysis.
• Formed by downgrowth of the brain during fetal development.
• Is in contact with the infundibulum.
• Nerve fibers extend through the infundibulum.
Posterior PituitaryPosterior Pituitary
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Hypothalamic Control of Hypothalamic Control of Posterior PituitaryPosterior Pituitary
• Hypothalamus produces:– ADH: paraventricular
nucleus
– Oxytocin: supraoptic nucleus
• Hormones transported along the hypothalamo-hypophyseal tract.
• Stored in posterior pituitary.
• Release controlled by neuroendocrine reflexes.
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• Master gland (also called adenohypophysis).
• Derived from a pouch of epithelial tissue that migrates upward from the mouth.
• Consists of 2 parts:• Pars distalis: anterior pituitary.• Pars tuberalis: thin extension in contact
with the infundibulum.
Anterior PituitaryAnterior Pituitary
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• Trophic effects:– Health of the target glands, depends
upon stimulation by anterior pituitary for growth.
– High plasma hormone concentration causes target organ to hypertrophy.
– Low plasma hormone concentration causes target organ to atrophy.
Anterior PituitaryAnterior Pituitary
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• Hormonal control rather than neural.
• Hypothalamus synthesizes releasing hormones and inhibiting hormones.
• Hormones are transported to axon endings of median eminence.– Delivers blood and hormones to anterior
pituitary via portal system.
Hypothalamic Control of the Hypothalamic Control of the Anterior PituitaryAnterior Pituitary
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• Anterior pituitary and hypothalamic secretions are controlled by the target organs they regulate.
• Negative feedback inhibition by target gland hormones.
Feedback Control of the Feedback Control of the Anterior PituitaryAnterior Pituitary
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Feedback Control of the Feedback Control of the Anterior PituitaryAnterior Pituitary
• Negative feedback at 2 levels:– The target gland hormone can act on the
hypothalamus and inhibit releasing hormones.
– The target gland hormone can act on the anterior pituitary and inhibit response to the releasing hormone.
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Adrenal GlandsAdrenal Glands
• Paired organs that cap the kidneys.• Each gland consists of an outer cortex and inner
medulla.• Adrenal medulla:
– Derived from embryonic neural crest ectoderm (sympathetic ganglia).
– Synthesizes and secretes:• Catecholamines (mainly epinephrine but some
norepinephrine).
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Adrenal MedullaAdrenal Medulla
• Innervated by sympathetic nerve fibers.– Increase respiratory rate. – Increase heart rate, cardiac output; and
vasoconstrict blood vessels, thus increasing venous return.
– Stimulate glycogenolysis.– Stimulate lipolysis.
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Thyroid HormonesThyroid Hormones• Thyroid gland located just below the
larynx.
• Thyroid is the largest of the pure endocrine glands.
• Follicular cells secrete thyroxine.
• Parafollicular cells secrete calcitonin.
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Production of Thyroid Production of Thyroid HormonesHormones
• I- (iodide) actively transported into the follicle and secreted into the colloid.
• Oxidized to (Io) iodine.• Iodine attached to tyrosine.
– Attachment of 1 iodine produces monoiodotyrosine (MIT).
– Attachment of 2 iodines produces diiodotyrosine (DIT).
• MIT and DIT or 2 DIT molecules coupled.
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Production of Thyroid Production of Thyroid HormonesHormones
• T3 and T4 produced.
• TSH stimulates pinocytosis into the follicular cell.– Enzymes hydrolyze to T3 and T4 from
thyroglobulin.
• Attached to thyroid-binding protein and released into blood.
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TT3 3 Effects Effects
• Stimulates cellular respiration by:– Production of uncoupling proteins.– Stimulate active transport Na+/ K+ pumps.– Lower cellular [ATP].
• Increases metabolic heat.• Increases metabolic rate.
– Stimulates increased consumption of glucose, fatty acids and other molecules.
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Parathyroid HormoneParathyroid Hormone
• Parathyroid glands embedded in the lateral lobes of the thyroid gland.
• Only hormone secreted by the parathyroid glands.
• Single most important hormone in the control of plasma Ca++ concentration.
• Stimulated by decreased plasma Ca++ concentration.
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PancreasPancreas
• Endocrine portion consists of islets of Langerhans.
• Beta cells secrete insulin– Stimulus is increase in plasma glucose
concentrations– Promotes entry of glucose into cells
• Alpha cells secrete glucagon– Stimulus is decrease in plasma glucose
concentrations– Stimulates lipolysis.
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Pineal GlandPineal Gland
• Melatonin:– Production stimulated by the suparchiasmatic
nucleus (SCN) in hypothalamus.– SCN is primary center for circadian rhythms.
• May inhibit GnRH.
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ThymusThymus
• Site of production of T cells (thymus-dependent cells), which are lymphocytes.
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Gonads and PlacentaGonads and Placenta
• Gonads (testes and ovaries):– Secrete sex hormones.
• Testosterone.• Estradiol.• Progesterone.
• Placenta:– Secretes large amounts of estrogen and
progesterone.
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ProstaglandinsProstaglandins
• Most diverse group of autocrine regulators.• Produced in almost every organ.• Wide variety of functions.
– Immune system:• Promote inflammatory process.
– Reproductive system:• Play role in ovulation.
– Digestive system:• Inhibit gastric secretion.
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ProstaglandinsProstaglandins
– Respiratory system:• May bronchoconstrict or bronchodilate.
– Circulatory system:• Vasoconstrictors or vasodilators.
– Urinary system:• Vasodilation.
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Good Luck ya 2ooroood