unit ix endocrine system and diseases chem 203 biochemistry
TRANSCRIPT
UNIT IX
Endocrine system and diseases
CHEM 203 Biochemistry
dr,Ola, F.A.Talkhan
dr,Ola, F.A.Talkhan
The survival of multicellular organisms depends on theirability to adapt to a constantly changing environment.
Intercellular communication mechanisms are necessaryrequirements for this adaptation.
The nervous system and the endocrine system provide this intercellular, organism- wide communication.
The nervous system was originally viewed as providing a fixed communication system.
the endocrine system supplied hormones, which are mobile messages.
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Endocrine vs Nervous system
Nervous system performs short term crisis management
Endocrine system regulates long term ongoing metabolic
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Definition of Hormone
HormoneIs a chemical messenger ,secreted in trace amounts by one type of
tissue and carried by the blood to the target tissue in the body to stimulate a specific biochemical or phsiological activity .
Endocrinology is the branch of medicine dealing with hormones, their normal or
physiological action and the diseases resulting from their abnormalities
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Endocrine glands:The glands secreting hormones are termed endocrine glands i.e. having no duct
Endocrine glands :1- hypothalamus gland 2- Pituitary gland3- thyroid gland4- parathyroid gland5- islet of pancreas6- adrenal gland5- pineal gland 6- thymus glands7-the sex organs: testes and ovaries
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Principal functions of the endocrine system
Maintenance of the internal environment in the body (maintaining the optimum biochemical environment).
Integration and regulation of growth and development.
Control, maintenance and instigation of sexual reproduction, including gametogenesis, coitus, fertilization, fetal growth and development and nourishment of the newborn.
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Recent classification of hormones Endocrine action: the hormone is distributed in blood and binds to distant target cells.
Paracrine action: the hormone acts locally by diffusing from its source to target cells in the neighborhood.
Autocrine action: the hormone acts on the same cell that produced it.
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Chemical classification of hormones
1- Proteins and Polypeptides- Hormones a. pituitary H b.Pancreas H c. Parathyroid gland H. d.hypothalamic H e. calcitonin f. gastroinestinal H
These hormones are stored in secretory vesicles until needed .
Usually released into blood stream via exocytosis .
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2- Amino acid derivatives hormones :
a.Thyroid and adrenal medullary hormones . They are derived from Tyrosine .
b. melatonin from tryptophan
c. GABA from glutamic acid
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3- Steroid hormones :
a. Hormones from adrenal cortex b. Sex H , male and female. c. 1,25 dihydroxy cholecalciferol
These hormones are usually synthesized from cholesterol and are not stored .
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Classification of hormones by mechanism of action
I. Hormones that bind to intracellular receptors
AndrogensCalcitriol (1,25[OH]2-D3)EstrogensGlucocorticoidsMineralocorticoidsProgestinsRetinoic acidThyroid hormones (T3 and T4)
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α2-Adrenergic catecholamines
β-Adrenergic catecholamines
Adrenocorticotropic hormone
Antidiuretic hormone
Calcitonin
Chorionic gonadotropin, human
Corticotropin-releasing hormone
Follicle-stimulating hormone
II. Hormones that bind to cell surface receptorsA. The second messenger is cAMP:
Glucagon
Lipotropin
Luteinizing hormone
Melanocyte-stimulating hormoneParathyroid hormone
Somatostatin
Thyroid-stimulating hormone
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Acetylcholine (muscarinic)
α1-Adrenergic catecholamines
Angiotensin II
Antidiuretic hormone (vasopressin)
Cholecystokinin
B. The second messenger is cGMP:Atrial natriuretic factor Nitric oxide
C. The second messenger is calcium or phosphatidylinositols (or both):
Gastrin
Gonadotropin-releasing hormone
Oxytocin
Platelet-derived growth factorSubstance P
Thyrotropin-releasing hormone
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D. The second messenger is a kinase or phosphatase cascade:Chorionic somatomammotropinEpidermal growth factorErythropoietinFibroblast growth factorGrowth hormoneInsulinInsulin-like growth factors I and IINerve growth factorPlatelet-derived growth factorProlactin
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Endocrine function of pancreaseInsulin and Glucagon: Control of Blood Glucose –
an example of antagonistic hormone pairs
The pancreas has clusters of endocrine cells called islets of Langerhans with:
alpha cells that produce glucagon and
beta cells that produce insulin
delta cell produce somatostatin
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insulinInsulin is a polypeptide hormone Is secreted as proinsulin then converted to insulin in Golgi.
A . In all species ,the molecule consists of two chains : A- chain : consists of 21 A.A. B- chain : consists of 30 A.A.
Two disulfide bridges connect between the two chain A third disulfide bond is present between A.A. no. 6 and no.
11 of the chain A
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Structure of human proinsulin. Insulin and C-peptide molecules are connected at two sites by dipeptide links.
An initial cleavage by a trypsin-like enzyme (open arrows) followed by several cleavages by a carboxypeptidase- like enzyme (solid arrows) results in the production of the heterodimeric (AB) insulin molecule (light blue) and the C-peptide.
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Metabolic actions of insulin
1- on carbohydrate metabolism :
Insulin reduces blood glucose levels by
Promoting the cellular uptake of glucose Stimulate glucose oxidation, glycogen synthesis Slowing glycogen breakdown in the liver Lipogenesis
The net result Hypoglycemic action
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2- on fat metabolism Lipogenic ( stimulate lipid synthesis ) Antilipolytic ( inhibits breakdown of lipids )Anti-ketogenic ( inhibits ketone bodies synthesis )Ketolytic ( stimulates ketone bodies breakdown)
3- on protein metabolism Anabolic ( increases protein synthesis)
Anticatabolic ( prevent protein breakdown.)
Produces a net gain of weight
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Homeostasis:Blood glucose level
(about 90 mg/100 mL)
Insulin
Beta cells ofpancreasrelease insulininto the blood.
STIMULUS:Blood glucose level
rises.
Liver takesup glucoseand stores itas glycogen.
Blood glucoselevel declines.
Body cellstake up moreglucose.
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GlucagonPolypeptide hormone secreted from the alpha cells of
pancreas.It is formed of 29 A.A.
Glucagon increases blood glucose levels by
Stimulating conversion of glycogen to glucose in the liverStimulating breakdown of fat and protein into glucose
i.e. hyperglycaemic and lipolytic
Remember: Glucagon – “Glucose ON!”
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Homeostasis:Blood glucose level
(about 90 mg/100 mL)
Glucagon
STIMULUS:Blood glucose level
falls.
Alpha cells of pancreasrelease glucagon.
Liver breaksdown glycogenand releasesglucose.
Blood glucoselevel rises.
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Somatostatin
Consists of 14 A.A. 1- Inhibit the release of insulin and glucagon 2- Inhibit the release of TSH and FSH and growth hormone (GH) .
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Diabetes Mellitus
Diabetes mellitus is perhaps the best-known endocrine disorder
It is caused by a deficiency of insulin or a decreased response to insulin in target tissues
It is marked by elevated blood glucose levels
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Thyroid Gland
thyroid gland formed of two lobes connecting by isthmus , present in the central portion of anterior aspect of the neck .
The Thyroid hormones include
1- T3 and T4
2-Calcitonin
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1- T3 and T4
Are synthesized from the amino acid tyrosine The synthesis occur in the follicles and involve :
1- iodination of tyrosine to form T1 and T2
2- coupling of either T1 and T2 to form T3 or T2 and T2 to form T4
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Thyroid hormones
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Function :
1- thyriod gland is essential for normal physical,mental and sexual growth
2- Regulators of various metabolic reactions
3- is important as regulator of differentiation during development
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Abnormalities of thyroid function :1- hyperthyroidism( thyrotoxicosis , toxic goiter )Charactrized by : a. enlargment of the thyroid gland with excessive production of thyroid hormone.
b.there is nervousness, rabid fatigability, excessive sweating ,increased body temperature and loss of weight
c. basal metabolic rate is increased
Goiter occurs when there is an iodine deficiency.
thiourea and thiouracil—for treatment of patients with thyrotoxicosis
Graves' disease is an autoimmune disease that affects the thyroid.
In Graves' disease the immune system makes antibodies that act like TSH, causing the thyroid to make more thyroid hormone than your body needs.
This is called an overactive thyroid or hyperthyroidism.
An overactive thyroid causes every function of the body to speed up, such as heart rate and the rate your body turns food into energy.
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Graves’ disease is a form of hyperthyroidism in humans
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2- hypothyroidism
a. in children result in cretinism
failure of normal physical , mental and sexual growth
b. in adults result in disease known as myxidoma
there is low physical and mental reactions with decreased basal metabolic rate and increased sensitivity to cold
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Feedback regulation of the secretion of the thyroid hormones
SomatostatinTHR
thyrotropin
thyroglobulin
T 3 and T4
Target organs
Hypothalamus
Anterior pituitary
Thyroid gland
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Parathyroid Hormone and Vitamin D Control of Blood Calcium
Two antagonistic hormones regulate the homeostasis of calcium (Ca2+) in the blood of mammals
Parathyroid hormone (PTH) is released by the parathyroid glands
Calcitonin is released by the thyroid gland
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Parathyroid GlandPTH parathormone ( hyper calcaemic hormone)Polypeptide hormone formed from 84 A.A. and secreted by
Parathyroid Gland raises calcium levels in blood – from bones and reuptake in
kidneys by : 1. increase mobilization of calcium from bones to blood 2. increase urinary excretion of phosphorus and increase
renal calcium reabsorption
3. increased calcium absorption from intestine by promotion of vit. D activation in kidney
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PTH
Parathyroid gland(behind thyroid)
STIMULUS:Falling blood
Ca2+ level
Homeostasis:Blood Ca2+ level
(about 10 mg/100 mL)
Blood Ca2+ level rises.
Stimulates Ca2+
uptake in kidneys
Stimulates Ca2+ release from bones
Increases Ca2+ uptake in intestines
Activevitamin D
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Calcitonin decreases the level of blood Ca2+
Calcitonin is a calcium lowering hormone secreted by thyroid gland
Is a polypeptide hormone formed of 32 A.A.
It stimulates Ca2+ deposition in bones and secretion by kidneysIt inhibits the formation of 1,25 dihydroxy cholecalciferol in
the kidney ( active form of vit. D )
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pineal glandMelatonin and BiorhythmsThe pineal gland is a small mass of tissue near the center of the brain.
This gland makes and secretes melatonin, a modified amino acid.
Melatonin’s primary functions are related to the biological rhythms associated with reproduction
Melatonin is derived from the amino acid tryptophan
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maintains the body's circadian rhythm, which is basically the day/night cycle
the pineal gland, produces more melatonin when it is dark. Reversely, when we are exposed to bright lights, the melatonin level drops.
Any kind of activity which may disrupt this normal cycle can give rise to pineal gland disorders.
tryptophan
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This gland makes me wake up in the morning and ready to go!
Pineal Gland
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Adrenal Hormones: Response to Stress
The adrenal glands are adjacent to the kidneysEach adrenal gland actually consists of two glands:
the adrenal medulla (inner portion)
and adrenal cortex (outer portion)
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Catecholamines from the Adrenal Medulla
The adrenal medulla secretes epinephrine (adrenaline) and norepinephrine (noradrenaline)
These hormones are members of a class of compounds called catecholamines
They are secreted in response to stress-activated impulses from the nervous system
They mediate various fight-or-flight responses
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Synthesis of catecholamines
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Epinephrine and norepinephrine
Trigger the release of glucose and fatty acids into the
blood
Increase oxygen delivery to body cells
Direct blood toward heart, brain, and skeletal muscles, and away from skin, digestive system, and kidneys
The release of epinephrine and norepinephrine occurs in response to nerve signals from the hypothalamus
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Stress
Adrenalgland
Nervecell
Nervesignals
Releasinghormone
Hypothalamus
Anterior pituitary
Blood vessel
ACTH
Adrenal cortex
Spinal cord
Adrenal medulla
Kidney
(a) Short-term stress response (b) Long-term stress response
Effects of epinephrine and norepinephrine:
2. Increased blood pressure3. Increased breathing rate4. Increased metabolic rate
1. Glycogen broken down to glucose; increased blood glucose
5. Change in blood flow patterns, leading to increased alertness and decreased digestive, excretory, and reproductive system activity
Effects ofmineralocorticoids:
Effects ofglucocorticoids:
1. Retention of sodium ions and water by kidneys
2. Increased blood volume and blood pressure
2. Possible suppression of immune system
1. Proteins and fats broken down and converted to glucose, leading to increased blood glucose
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(a) Short-term stress response
Effects of epinephrine and norepinephrine:
2. Increased blood pressure
3. Increased breathing rate
4. Increased metabolic rate
1. Glycogen broken down to glucose; increased blood glucose
5. Change in blood flow patterns, leading to increased alertness and decreased digestive, excretory, and reproductive system activity
Adrenalgland
Adrenal medulla
Kidney
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The adrenal cortex releases a family of steroids called corticosteroids in response to stress
These hormones are triggered by a hormone cascade pathway via the hypothalamus and anterior pituitaryHumans produce two types of corticosteroids:
1- glucocorticoids 2- mineralocorticoids
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(b) Long-term stress response
Effects ofmineralocorticoids:
Effects ofglucocorticoids:
1. Retention of sodium ions and water by kidneys
2. Increased blood volume and blood pressure
2. Possible suppression of immune system
1 . Proteins and fats broken down and converted to glucose, leading to increased blood glucose
Adrenalgland
Kidney
Adrenal cortex
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Glucocorticoids, such as cortisol, influence glucose metabolism and the immune system
Mineralocorticoids, such as aldosterone, affect salt and water balance
The adrenal cortex also produces small amounts of steroid hormones that function as sex hormones
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Abnormalities of adrenal gland
1-Addison’s disease ( hypofunction of adrenal cortex)
2- Cushing’s disease (hyperfunction of adrenal cortex)
3- pheochromocytoma : tumour in adrenal that release excessive catecholamines with :
a.hypertension b.Glucosuria
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Gonadal Sex Hormones
The gonads, testes and ovaries, produce most of the sex hormones: androgens, estrogens, and progestins
All three sex hormones are found in both males and females, but in different amounts
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Androgens
The testes primarily synthesize androgens, mainly testosterone, which stimulate development and maintenance of the male reproductive system
Testosterone causes: an increase in muscle and bone mass and is often
taken as a supplement to cause muscle growth, which carries health risks
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Actions and functions of testosterone
1- stimulation of development of accessory sex organ
2- responsible for development and maintenance of accessory sexual characters
3-protein anabolic effect and growth promotion
4- stimulation and maintenance of spermatogenesis
5- an inhibitory effect( feed back) on pituitary LH secretion
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Estrogens
Estrogens, most importantly estradiol, are responsible for maintenance of the female reproductive system and the development of female secondary sex characteristics
In mammals, progestins, which include progesterone, are primarily involved in preparing and maintaining the uterus
Synthesis of the sex hormones is controlled by FSH and LH from the anterior pituitary
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The HypothalamusSmall structure at the base of
the brain
Regulates many body functions, including appetite
and body temperature
Regulates the pituitary gland
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Coordination of Endocrine and Nervous Systems in Vertebrates
The hypothalamus receives information from the nervous system and initiates responses through the endocrine system
Attached to the hypothalamus is the pituitary gland composed of:
1-the posterior pituitary and 2-anterior pituitary
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The posterior pituitary stores and secretes hormones that are made in the hypothalamus
The anterior pituitary makes and releases hormones under regulation of the hypothalamus
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Spinal cord
Posteriorpituitary
Cerebellum
Pinealgland
Anteriorpituitary
Hypothalamus
Pituitarygland
Hypothalamus
Thalamus
Cerebrum
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HypothalamusThe hypothalamus secretes two hormones which are
stored in the posterior pituitary.
1) oxytocin – induces uterine contractions during birth and milk production
2) ADH – which decreases urine volume
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Posteriorpituitary
Anteriorpituitary
Neurosecretorycells of thehypothalamus
Hypothalamus
Axon
HORMONE OxytocinADH
Kidney tubulesTARGET Mammary glands,uterine muscles
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The anterior pituitary gland secretes releasing hormones and inhibiting hormones.
TSH – thyroid stimulatingFSH and LH – stimulates gonadsACTH - stimulates adrenal cortexProlactin – milk productionMSH – stimulates production of melanocytes (skin
pigments)GH – growth hormone
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Hypothalamicreleasing andinhibitinghormones
Neurosecretory cellsof the hypothalamus
HORMONE
TARGET
Posterior pituitary
Portal vessels
Endocrine cells ofthe anterior pituitary
Pituitary hormones
Tropic effects only:FSHLHTSHACTH
Nontropic effects only:ProlactinMSH
Nontropic and tropic effects:GH
Testes orovaries
Thyroid
FSH and LH TSH
Adrenalcortex
Mammaryglands
ACTH Prolactin MSH GH
Melanocytes Liver, bones,other tissues
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Tropic Hormones
A tropic hormone regulates the function of endocrine cells or glands
The four strictly tropic hormones are Thyroid-stimulating hormone (TSH) Follicle-stimulating hormone (FSH) Luteinizing hormone (LH) Adrenocorticotropic hormone (ACTH)
Anterior Pituitary
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Hormone Anterior Pituitary
Target Chemical Structure
Function
Adrenocortico-trophic
Hormone (ACTH)
Adrenals 39 Amino Acids
Stimulates the adrenal gland to produce hormones called: Cortisol (Glucocorticoid) Aldosterone (Mineralocorticoid)Testosterone (Androgen)Dehydroepiandrosterone sulfate (precursor of Estrogen)Cortisol promotes normal metabolism,
• maintains blood sugar levels and blood pressure. • It provides resistance to stress and acts as an inflammatory agent. •It also helps to regulate fluid balance in the body.
Thyroid stimulating hormone
(TSH)
Thyroid Glycoprotein2 polypeptide
chain(α and β)
Stimulates the Thyroid Gland to secrete its own hormone called Thyroxine (T4). It stimulates the thyroids through G-protein coupled receptors . Another hormone produced from the thyroid is called tri-iodothyronine or T3. Thyroxine controls many bodily functions, including heart rate, temperature ,growth and metabolism. It also helps metabolise calcium in the body.
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Anterior Pituitary Hormone Contd;Leutenising Hormone
(LH)
&
Follicle- Stimulating Hormone
(FSH)
Ovaries (females)
Testes (males)
Glycoprotein
2 Polypeptide Chain
(α and β)
Control reproduction and sexual characteristics. Stimulate the ovaries to produce Estrogen and Progesterone and the testes to produce Testosterone and sperm. LH and FSH are also known collectively as gonadatrophins.Estrogen helps with growth of tissue of the sex organs and reproductive parts. It strengthens bones and has a positive effect on the heart. Testosterone is responsible for the masculine characteristics including hair growth on the face and body and muscle development. It is essential for producing sperm and strengthening the bones.
Prolactin Breasts Protein198 amino acids
Stimulates the breasts to produce milk and is secreted in large amounts during pregnancy and breastfeeding.
It is however present at all times in both males and females.
Growth Hormone
(GH)
All cells in the body
Protein191 AA
In children this hormone is essential for a normal rate of growth. It stimulates the release of IGF-1 (Somatomedin).In adults it controls energy levels and well-being. It is important for maintaining muscle and bone mass and appropriate fat distribution in the body.
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Hormone Posterior Pituitary
Target Chemical Nature
Function
Antidiuretic Hormone
(ADH) Vasopressin
Kidneys
Peptide 9 amino acids
Controls the blood fluid and mineral levels in the body by affecting water
retention by the kidneys ( water reabsorption).
OxytocinUterus
& Breasts
Peptide 9 amino acids
Affects the uterine contractions in childbirth and the subsequent
release of milk for breast feeding.
labor and delivery, milk ejection,(pair bonding)
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Hormone Excessive release dificiency
Growth hormone
Acromegaly ( children) Gigantism ( adults ) Dwarfism
Prolactin Ammenorrhae
Infertility galactorrhoea
Failure of lactation
ACTH Cashing’s disease Secondary adrenocortical hypofunction
TSH Hyperthyrodism(Very rare cause )
Myxoedema( secondary hypothyrodism)
LH\FSH Precocious puberty Secondary hypogonadism Infertility
Effects of abnormalities of pituitary hormones secretion
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Dwarfism :Result from growth hormone deficiency Dwarfs remain short but their mentality and sexuality is normal.
Acromegaly and Gigantism:Hyperfunction of anterior pituitary due to tumours in the gland.Acromegaly:in acromegaly the epiphyses are already closed so the growth will be more in the width with protrusion of jaws , enlargement of nose , hands, feet and internal organs with thickening of skin .Gigantism:In gigantism the long bones increase in length and the patient reaches an usual height (will be very tall).In both there will be metabolic changes as: hyperglycaemia , glucosuria , hyperlipidaemia … etc.