Endocrine...Hormones act on target tissues through binding to their specific receptors - On the cell...
Transcript of Endocrine...Hormones act on target tissues through binding to their specific receptors - On the cell...
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Dr. Adel Hussien
Assistant Prof. of Physiology
Physiology dept.-Faculty of
Medicine – Minia University
Endocrine
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Introduction to the endocrine system
Learning objectives:
What is the endocrine system?
What is the hormone?
- Chemical nature of hormones
- Mechanism of action of hormones
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Introduction to Endocrine System
Endocrine glands: glands that secrete hormones directly into blood
stream to affect target tissues & organs all over the body
(notice the difference from exocrine glands)
Pituitary gland is the master of endocrine glands
and pituitary itself is under control of hypothalamus
Major endocrine glands:
- Thyroid
- Parathyroid
- Suprarenal gland (cortex & medulla)
- Gonads (testes & ovaries)
- Pancreas (islets of Langerhans)
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Connection between hypothalamus and pituitary
1- Hypothalamo-hypophyseal portal
circulation
Circulaton between the hypothalamus
& anterior pituitary..carry releasing or
inhibiting hormones from hypothalamus
to affect secretion of anterior pituitary
gland
e.g. TSH, ACTH, FSH &LH…
2- Hypothalamo-hypophyseal tract
Nerve fiber connection between the hypothalamus and posterior
pituitary.. ADH & oxytocin hormone formed in
hypothalamus..released & stored in the posterior pituitary gland
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Hormones
These are chemical substances secreted by specific cells (endocrine
glands) directly into the blood to affect nearby or distant target cells
(i.e. chemical messengers)
Chemistry of hormones:
1- proteins & Polypeptides: pituitary, pancreatic, parathyroid &
hypothalamic hormones
2- Steroid hormones (derived from cholesterol): suprarenal cortex
hormones, sex hormones & vitamin D derivatives
3- Tyrosine derivatives (single amino acid): thyroid hormones &
catecholamines
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Feedback control of hormone secretion
* According to the type
1- Negative feedback
2- Positive feedback
.
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*According to distance of feedback
1- Long loop feedback
The hormone secreted by the endocrine
gland affects hypothalamus and anterior
pituitary gland
2- Short loop feedback
The hormone secreted by anterior pituitary
affects the hypothalamus
3- Ultra short loop feedback
The hormone secreted by the
hypothalamus return and affecting the
Hypothalamus again
(autocrine effect)
Ultra
short
loop
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Hormone receptors:
Hormones act on target tissues through binding to their specific receptors
- On the cell membrane of tissues e.g. protein hormones
- In the cytoplasm e.g. steroid hormones
- In the nucleus e.g. Thyroid hormones
These receptors are specific to each hormone
There response is changed with various stimuli according to metabolic needs
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Mechanisms of hormone action
Binding of hormones to their receptors…formation of hormone-receptor
complex…act by one of the following mechanisms
1- Genomic mechanism: transcription of DNA (genetic
material)…mRNA..synthesis of enzymes
2- Non genomic mechanism: No DNA transcription, but activation of a
cell membrane or cytoplasmic mechanism. Increase intracellular
second messenger like cAMP, cGMP, calcium
3- Combined genomic and non genomic mechanism
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The pituitary gland (Hypophysis cerebri)
Learning objectives:
- Hormones secreted by the anterior pituitary gland
- Regulation of anterior pituitary hormones secretion
- Disorders of pituitary hormones secretion (GH)
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The pituitary gland is functionally divided into
1- Anterior pituitary (anterior lobe, adenohypophysis)
2- Posterior pituitary (posterior lobe, neurohypophysis)
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Hormones of anterior pituitary
The anterior pituitary produces and
secretes the following hormones:
1- GH Growth hormone ( from somatotropes)
Somatotrophic hormone, somatotropin
2- TSH Thyroid stimulating hormone (from
thyrotropes)
Thyrotrophic hormone, thyrotropin
3- FSH, LH (from gonadotropes)
Gonadotrophic hormones, gonadotropins
4- ACTH Adrenocorticotrophic hormone
(from corticotropes)
Corticotrophic hormone, corticotropin
5- Prl Prolactin (from mammotropes)
Mammotrophic hormone, mammotropin
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Hypothalamic control of anterior pituitary:
The hypothalamus release the following
hormones (factors) into the hypothalamic
Hypophyseal portal circulation to control
anterior pituitary hormones secretion
1- GHRH Growth hormone releasing hormone
2- GHIH Growth hormone inhibiting hormone (somatostatin)
3- TRH Thyrotropin releasing hormone
4- GnRH Gonadotropin releasing hormones
5- CRH Corticotropin releasing hormone
6- PIH Prolactin inhibiting hormone
(Dopamine)
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Growth Hormone (GH, Somatotropin)
It is a protein hormone about 191 amino acids secreted in pulsatile
pattern from
Physiological functions:
I- Effect on growth: GH increases protein synthesis, cell division and
proliferation…increase size and number of cells…growth of body
tissues
(1) Soft tissues: increase size of tissues and organs as heart, lung,
stomach..
(2) Skeleton:
A- Before puberty (before union of epiphysis with the shaft of long
bones GH stimulates
- Differentiation of chondrocytes into osteogenic cells..increase protein
deposition by these cells..deposition of new bones
- Chondrocytes…local production of insulin like growth factor1 (IGF1)
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..increased growth of epiphyseal cartilage and conversion into new
bone..elongation of the shaft..increase linear growth of bone
- Osteoblasts in bone periosteum..deposition of new bone on the bone
surface…increase thickness of bones
B- After puberty (after union of epiphysis)
GH increase only the thickness of bones No increase in linear growth
The effect of growth hormone on growth is indirect through
somatomedins
Somatomedins:
- Polypeptides secreted by liver and other tissues as cartilage
- Their effects on growth similar to those of insulin (insulin like actions)
- The most important among 4 types is somatomedin C (IGF1)
produced by the liver and chondrocytes
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II- Effects on metabolism
(1) Protein metabolism: anabolic (increase body protein) through
- Increase amino acids uptake & transport into the cells
- Increase transcription of DNA, formation of mRNA, and translation of
RNA…increase protein synthesis
- Decrease protein catabolism.. Inhances uses fatty acids for energy
production and spare protein
(2) Carbohydrate metabolism: Hperglycaemic, diabetogenic effect
- Increase glucose production by the liver & increase gylcogenesis &
glycogen deposition
- Decrease glucose uptake by cells (inhibition of glucokinase in skeletal
muscles and fat cells)
- Decrease glucose utilization by cells (decrease glycolysis & glucose
oxidation)
.
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(3) Fat metabolism: lipolytic and ketogenic effect
- GH stimulates lipolysis (destruction of fat) & mobilization of free
fatty acids (FFA) from adipose tissue to blood…hyperlipidaemia
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Regulation of GH secretion
(1) Hypothalamic control: through
- Growth hormone releasing
hormone (GHRH)
- Growth hormone inhibiting
hormone (GHIH, Somatostatin)
(2) –ve feedback control:
- Long loop feedback:
IGF1 at pituitary &
hypothalamic level
- Short loop feedback:
between GH & GHRH
- Ultra short loop feedback:
GHRH on itself
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Factors affecting GH secretion
A- Factors increasing GH secretion:
1- Decrease blood glucose & FFA level
2- Fasting & starvation
3- Protein meal & I.V. injection of amino acids
4- Exercise
5- Start of deep sleep
6- Sex hormones, estrogens & androgens
B- Factors decreasing GH secretion:
1- Increase blood glucose & FFA level
2- Obesity
3- Aging
4- Some hormones, cortisol, somatostatin & exogenous GH
.
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Disturbances of GH function
The disturbance may be
1- GH hypofunction : due to decreased GH secretion
2- GH hyperfunction: due to increased GH secretion
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1- Effects of GH hypofunction
A- Pituitary dwarfism: Occurs due to the following causes
1- Decrease GH secretion from anterior pituitary
2- Decrease GHRH secretion from hypothalamus
3- Decrease IGF1 secretion from liver and chondrocytes
Levi-Lorain dwarf: GH secretion is normal or even high but there is hereditary inability to form somatomedin C
4- Laron dwarfism: GH receptors defect that leads to insensitivity to GH
Characters:
1- Physical growth: arrested growth of the child
- Short stature (100-120cm)
- Proportionate decrease in size of trunk and extremities (span=hight & vertex to symphysis= symphysis to heel)
2- Sexual & mental development: normal
Some of them are intelligent but may be psychologically unstable
B- Pituitary infantilism: Pituitary dwarfism+hypogonadism due to additional decrease in gonadotrphic hormones
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2- Effects of hyperfunction
A- Gigantism (Giantism)
Cause: acidophilic adenoma..increase GH secretion before union of
epiphysis of long bones (Before puberty, prepubertal)
Characters: symmetrical growth of soft tissues and skeleton
1. The patient becomes very tall, may reach 3 meters in height
(span=height & vertex to symphysis= symphysis to heel)
2- Hyperglycaemia, glucosuria & diabetes mellitus (DM in 10% of
cases)
3- Hypogonadism due to pressure on basophil cells secreting GnHs
4- Ends in panhypopituitarism and death due to destruction of all cells of
the pituitary
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B- Acromegaly:
Cause: increase GH secretion after union of epiphysis of long bones
(after puberty, postpubertal)
Characters:
1. Skeletal growth: No linear growth of long bones but all bones of the
body (flat & long) increase in thickness .
- Hands and feet become large & broad
- Skull, box shaped with prominent cheeks, nasal bones,superciliary
ridges
- Mandible, protruded lower jaw (prognathism) & widely separated
teeth
- Kyphosis (spine bends) due to over growth of vertebrae
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2. Soft tissue growth
- Overgrowth of skin & soft tissues of the face…wrinkling of the scalp
& forehead ( bulldog facies)
- Overgrowth of muscle & viscera, patient very strong for few years
then becomes weak
3. Hyperglycaemia & glucosuria & 2ry diabetes may occur later in the
disease due to exhaustion of beta cells of pancreas
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Hormones of posterior pituitary
1- Antidiuretic hormone (ADH-Vasopressin)
Functions:
1- On the kidney
ADH increases water reabsorption by distal convoluted and collecting
tubules of the kidney…..decrease urine volume
2- On smooth muscle in blood vessels
In excess doses it leads to generalized vasoconstriction….increases
blood pressure
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Control of ADH secretion
1- Osmotic pressure of plasma
Increase osmotic pressure of plasma (as in dehydration)…increase
ADH secretion
Decrease osmotic pressure of plasma (as in overehydration)…dncrease
ADH secretion
2- Volume of extracellular fluid (ECF)
Marked decrease in blood volume (as in hemorrhage)…increase ADH
secretion while increased blood volume has the opposite effect
3- Nervous factors
Stressful stimuli….increase ADH secretion
Cold exposure…..decrease ADH secretion
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Dirorders of ADH secretion
Diabetes insipidus (DI)
Causes:
- Decrease ADH secretion due to lesion in the hypothalamus
(neurogenic DI)
- Nephrogenic DI is due to abnomality in ADH receptors of the kidney
(ADH secretion is normal)
Manifestations of DI:
- Polyuria: increased urine formation (may reach 20liters/day)
- Polydypsia: excessive water intake
- Loss of water soluble vitamins in urine
- Marked increase in basal metabolic rate (BMR)
Neurogenic DI responds to exogenous ADH administration but
nephrogenic DI does not.
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2- Oxytocin
Functions:
1- Milk ejection
2- Contraction of uterus
3- Slight vasoconstrictor and antidiuretic effect
Control of secretion:
Oxytocin increases by reflex action
- During Suckling
- During Labor