Post on 01-Jul-2015
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ENDOCRINOLOGY
Dr Maie Al-Bader
Dept. of Physiology
Ext: 6355
E-mail: albader@hsc.edu.kw
Dr. Maie Al-Bader - Endocrinology 2013 1
ENDOCRINOLOGY
• The main function of the endocrine system is to maintain
the homeostasis of the internal environment
• Hormone: chemical messengers secreted by cells of
endocrine glands (ductless glands) and tissues that
regulate the activity of other cells in the body.
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Endocrine Glands that Function
Primarily to Secrete Hormones 1. Pituitary gland: ADH (vasopressin), oxytocin &
trophic hormones
2. Thyroid gland: thyroxine, tri-iodothyronine &
calcitonin
3. Parathyroid gland: parathyroid hormone
4. Adrenal gland: cortisol, aldosterone,
epinephrine & sex steroids
5. Pancreas: insulin and glucagon
6. Ovaries & testicles: androgens, estrogens &
progesterone
7. Pineal gland: melatonin
8. Thymus gland: thymosine
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Other Organs which Function
Secondarily as Endocrine Glands
1. Heart: atrial natriuretic peptide (ANP)
2. Kidney: erythropoietin
3. Liver: somatomedin (IGF)
4. Skin: vitamin D3
5. Gastrointestinal tract: gastrin, CCK and VIP
6. Adipose tissue: leptin
7. Hypothalamus: releasing and inhibiting hormones
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Mechanism of Hormone Action
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Functional categories of hormones based on the location of their
receptor proteins and mechanisms of action:
a. Hormones that bind to nuclear receptor proteins e.g. steroid
and thyroid hormones (what would be the characteristics of such
hormones?)
b. Hormones that use second messengers e.g. protein and
peptide hormones (what would be the characteristics of such hormones?)
Hormones that Bind to
Nuclear Receptor Proteins Steroids
Lipohilic steroid hormones are
bound to carrier proteins in
plasma. They then dissociate
from these proteins in order to
pass through the lipid
component of the target cell
membrane and enter target cell
where their receptor proteins
are located
Secreted by: adrenal cortex,
testes and ovaries
Location of receptors: in
cytoplasm or nucleus of the
target cell
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Thyroid Hormones
Very similar to steroids in size; being non-polar; and very water-insoluble; carried
mainly by thyroxine-binding globulin (TBG; T4 more than T3)
Secreted by: thyroid gland
Location of receptor proteins: are in the nucleus of target cells
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Hormones that Use Second
Messengers Catecholamines (epinephrine and
norepinephrine), polypeptides and
glycoproteins cannot pass the lipid
bilayer of the cell membrane and
thus mediate their effects through
second messengers
Secreted by: all glands EXCEPT
adrenal cortex, gonads and
thyroid
Location of receptors: outer
surface of the membrane
Effects of hormone-receptor
interaction: stimulates production
of intracellular second messenger
including c-AMP, c-GMP,
phospholipase C, Ca2+ and
tyrosine kinase
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Pituitary Gland (Hypophysis)
The pituitary gland is divided into two lobes:
1. Anterior hypophysis (adenohypophysis)
2. Posterior pituitary or neurohypophysis (neural part of the pituitary; pars
nervosa)
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Posterior Pituitary Hormones
Posterior pituitary secretes only two hormones which are:
Produced by the hypothalamus
Stored in the posterior pituitary
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Antidiuretic hormone (ADH)
• Also known as arginine vasopressin (AVP)
• It stimulates retention of water by the kidneys
Oxytocin
In females:
• It stimulates the contraction of the uterus during labour (required for
parturition; childbirth)
• It stimulates milk-ejection reflex in a lactating woman, i.e., contractions of
the mammary gland alveoli and ducts
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Control of ADH & Oxytocin Secretion by Neuro-Endocrine Reflex
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Anterior Pituitary Hormones
Secreted by pars distalis of adenohypophysis
They include:
Thyroid-stimulating hormone (TSH)
Adrenocorticotropic hormone (ACTH)
Follicle-stimulating hormone (FSH)
Luteinizing hormone (LH)
Prolactin
Growth hormone (GH) or somatotropin
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Hyposecretion of growth hormone:
During childhood pituitary dwarfism (with normal body proportions)
During adulthood Simmonds’ disease
Hypersecretion of growth hormone:
During childhood gigantism
During adulthood acromegaly (no further growth BUT person’s
appearance changes as a result of thickening of bones, growth of soft
tissues as in face, hands and feet)
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Control of Secretion of
Anterior Pituitary Hormones
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1. Hypothalamic control: achieved through hormonal control 2. Feedback control by hormones secreted from target gland
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STIMULATE INHIBIT
CRH: Corticotropin-releasing hormone
GnRH : Gonadotropin-releasing hormone
TRH: Thyrotropin-releasing hormone
PIH or dopamine: Prolactin-inhibiting hormone
GHRH: Growth hormone-releasing hormone
ANTERIOR PITUITARY ACTH LH & FSH TSH PRL GH
HYPOTHALAMUS CRH TRH GHRH DOPAMINE
(PIH) GnRH
1. Hypothalamic Control
2. Feedback Control Of Anterior Pituitary
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Secretion of ACTH, FSH, LH and TSH is controlled by negative feedback
inhibition:
•Target gland hormones hypothalamus
•Target gland hormones anterior pituitary
•Anterior pituitary hypothalamus
• The adrenal medulla cells secrete catecholamines (epinephrine and norepinephrine;
4:1 ratio) and are innervated by sympathetic nerve fibers; activated by stress
• Once simulated the actions are
• very similar to those caused by stimulation of sympathetic nervous system,
however, they last ten times longer
• Activation of both the adrenal medulla and the sympathetic nervous system
prepares the body for greater physical performance (fight-or-flight)
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Each adrenal gland consists of adrenal cortex and adrenal medulla
Adrenal Glands
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Adrenal Cortex Secretes steroid hormones called corticosteroids (corticoids) including
mineralocorticoids, glucocorticoids and sex steroids
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Mineralocorticoids (Aldosterone):
• Zona glomerulosa
• Secretes aldosterone which acts on the kidneys to regulate Na+ and K+
balance
Glucocorticoids (Cortisol):
• ACTH stimulates the zona fasiculata (little in zona reticularis) to secrete cortisol.
• Cortisol is a catabolic hormone that acts on the liver, muscle & adipose tissues
(to regulate carbohydrate, protein and fat metabolism) leading to an:
• serum glucose
• serum free fatty acid
• serum amino acid
Sex steroids:
• Weak androgens secreted by zona reticularis of adrenal cortex
• Supplement of sex steroids secreted by the gonads
Adrenal Cortex Secretion Abnormalities
1. Cushing's syndrome/disease:
Cause: hypersecretion of corticosteroids as a result of:
tumor of adrenal cortex (Cushing’s syndrome)
oversecretion of ACTH from anterior pituitary (Cushing’s disease)
(what are the two main differences between the syndrome and disease?)
Characterized by:
hyperglycemia
hypertension
muscular weakness
structural changes: moon face, purple abdominal striae, truncal obesity, buffalo hump and spindly arms and feet
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2. Addison’s disease:
Cause: inadequate secretion of cortisol and aldosterone
Characterized by:
hypoglycemia
Na+ loss and K+ retention
dehydration
hypotension
rapid weight loss
generalized weakness
May lead to death if not treated with corticosteroids
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3.Adrenogenital syndrome:
Cause: hypersecretion of adrenal sex hormones, particularly androgens
• In young children premature puberty and enlarged genitals
• In mature women growth of beard
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Thyroid Glands
• Secretes
• thyroxine (T4)
• triiodothryonine (T3)
• calcitonin
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Production and Storage of Thyroid Hormones
Target organ: almost all body organs
• Actions:
• stimulates protein synthesis
• promotes proper skeleton growth and development
• promotes maturation of the CNS
• its level in the blood determines the BMR (the minimum rate of caloric expenditure by the body)
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Hypothyroidism
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1. Iodine-deficiency (endemic goitre): form of hypothyroidism, caused by the lack
of adequate iodine in the diet
2. Cretinism: newborn infants born in areas of low iodide intake and endemic
goitre. Symptoms include : mental retardation, short stature, puffy face and
hands, deaf mutism etc.
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3. Infantile hypothyroidism: occurs during childhood. Symptoms include: retarded
growth, abnormal bone development, low IQ, general lethargy and low body
temp
4. Hashimoto thyroiditis: form of hypothyroidism, characterized by a goitre, high
concentrations of antibodies, which are directed against thyroglobulin and
thyroid peroxidase. The progressive destruction of thyroid follicular tissue results
in hypothyroidism
5. Myxoedema: hypothyroidism in adulthood. Symptoms include: edema, low basal
metabolic rate, low body temperature, cold intolerance, lethargy and weight gain
tendency
Hyperthyroidism
Graves’ Disease
(Toxic Goitre)
• It is an autoimmune disease caused by antibodies that act like TSH causing
the growth of the thyroid associated with hypersecretion of thyroxine
• Clinical symptoms include:
• BMR
• heart rate
• weight loss
• excessive sweating
• heat intolerance
• exophthalamus (bulging of the eyes; because of edema in tissues of eye
socket)
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Regulation of Calcium and Phosphate
Ca2+ and phosphate concentration in plasma is affected by:
• Bone resorption and absorption
• Intestinal absorption
• Urinary excretion
Regulation of plasma calcium and phosphate BY:
• Parathyroid hormone
• Calcitonin
• Calcitriol (1,25-dihydroxyvitamin D3)
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Parathyroid Hormone (PTH)
• PTH is secreted by the parathyroid glands (usually 4) whenever the plasma
concentration of Ca2+ begins to fall
• PTH promotes a rise in blood calcium levels by acting on:
• Bones: stimulating bone resorption
• Kidneys: reabsorbtion of Ca2+ from glomerular filtrate and inhibiting reabsorption
of phosphate
• Intestine (indirect) : promoting the formation of 1,25-dihydroxyvitamin D3 by
stimulating 1a-hydroxylase in the kidney
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Calcitriol
(1,25-dihydroxyvitamin D3)
• Production starts in the skin where Vitamin D3 is produced from precursor molecule 7-
dehydrocholesterol under the influence of sunlight
• Actions:
• Activity stimulated by PTH
• Helps to raise plasma concentration of calcium and phosphate by stimulating:
• Intestinal absorption of calcium and phosphate (main function)
• Resorption of bones
• Renal reabsorption of calcium and phosphate
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Calcitonin
• Calcium lowering hormone
• Secreted by the parafollicular cell in
the thyroid gland
• It antagonizes the hypercalcemic
effect of calcitriol and PTH
• Is stimulated by high plasma Ca2+
and phosphate levels and acts to
lower Ca2+ levels by:
• inhibiting bone resorption
• stimulating the urinary excretion
of Ca2+ and phosphate by
inhibiting their reabsorption by the
kidneys
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Osteoporosis
• Osteoporosis is characterized by low bone mass (due to the reduced deposition of
collagen as well as mineral). It occurs when bone resorption exceeds formation
• The bones become fragile & susceptible to fracturing (mainly hip, spine and wrist)
• Weight-bearing exercise builds denser, stronger bones (age 25 to 30). Weight-
lifting, jogging, hiking, stair-climbing, step aerobics, dancing, racquet sports, and
other activities that require your muscles to work against gravity.
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Pancreas
The pancreas consists of an endocrine and an exocrine portion.
The exocrine portion is important for production of both bicarbonate and digestive enzymes
The endocrine portion of the pancreas consists of pancreatic islets (islets of Langerhans)
There are 2 types of cells in the islets of Langerhans:
alpha cells: secrete glucagon
beta cells: secrete insulin
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Abnormalities – Diabetes Mellitus
• DIABETES MELLITUS is characterized by:
• Fasting hyperglycemia
• Glucose in the urine
• Type I diabetes (also known as juvenile-onset diabetes or insulin-dependent
diabetes mellitus [IDDM]). It occurs:
• in 10% of cases
• when there is lack of insulin secretion as a result of destruction of the beta
cells
• Type II diabetes (also known as maturity-onset diabetes or insulin independent
diabetes mellitus [NIDDM]). It occurs:
• in 90% of cases of diabetes
• patients are usually overweight
• there is a larger amount of insulin secretion, however, decreased tissue
sensitivity to insulin
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Long Term Complications of Diabetes Mellitus
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