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Hormonas Tiroideas
Dr. Victor J. Samillan
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Figure 18.2
Hormones
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thyroid
trachea
larynx
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The Thyroid Gland
Figure 18.11b,
c
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Precursor molecule (Tyr) and
intermediates (MIT, DIT) duringthyroxine biosynthesis
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Thyroxine (T4)
3,5,3´,5´-tetraiodothyronine
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3,5,3´-triiodothyronine (T3)
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Control of thyroid hormone synthesis
and secretion
Pituitary hormone thyreotropin (TSH)upregulates activity of iodide pump of folliclecells of thyroid gland
Endocytosis of iodinated thyreoglobulin andfollowing secretion of T3 and T4 is alsoupregulated by TSH
Production of TSH is upregulated by TRH andcontroled by thyroid hormones via negativefeedback
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Mechanism of thyroid hormone
action
Receptors for thyroid hormones are nuclear and its affinityis tentimes higher for T3 than T4
The amount of nuclear receptors is very low
Four variants of nuclear receptor were observed andmitochondrial receptor for T3 was also described
Free thyroid hormone receptor (TR) without boundhormone is bound to hormone response element of DNA(HRE) and corepressor (CoR)
After binding T3 to receptor - CoR is liberated andcoactivators (CoA) is bound and the transcription tomRNA begins
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Hormone Effects on Gene
Activity
Figure 18.4
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Thyrotropin-releasing hormone (TRH) increases the secretion of thyrotropin (TSH), which stimulates the synthesis and secretionof trioiodothyronine (T3) and thyroxine (T4) by the thyroid gland. T3 and T4 inhibit the secretion of TSH, both directly andindirectly by suppressing the release of TRH. T4 is converted to T3 in the liver and many other tissues by the action of T4monodeiodinases. Some T4 and T3 is conjugated with glucuronide and sulfate in the liver, excreted in the bile, and partiallyhydrolyzed in the intestine. Some T4 and T3 formed in the intestine may be reabsorbed. Drug interactions may occur at any of these sites.
Pathways of thyroid hormone metabolism
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Mechanisms increasing body
temperature during hyperthyroidismReducing efficiency of ATP synthesis - increased
synthesis of glycerol 3-phosphate dehydrogenase – increased transport NADH by this shuttle than
malate/aspartate shuttle
Increased synthesis of ATP
Increased consumption of ATP
Uncoupling of phosphorylation and oxidation inmitochondria
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Increased respiration during
hyperthyroidism
Increased synthesis of ATP – increased synthesis of cytochrome c oxidase – increased oxidativephosphorylation (it means the increased consumptionof oxygen) – increased production of ATP
Increased consumption of ATP – increased synthesis of various ATPase (eg. Ca dependent in muscles) – increased depletion of store of ATP
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Increased expression of proteins by
thyroid hormones
Glycerol 3-phosphate dehydrogenase –
maincomponent of glycerol 3-phosphate shuttle inmitochondria (one of transport systems for NADHinto mitochondria)
Cytochrome c oxidase –
the complexmitochondrial enzyme in the electron transportchain (from cytochrome c to oxygen)
ATPases – (eg. Ca ATPase of muscle cells)
Carbamyl phosphate synthase –
enzyme of urea cycle
Growth hormone
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System Thyrotoxicosis Hypothyroidism
Skin and appendages Warm, moist skin; sweating; heatintolerance; fine, thin hair;
Plummer's nails; pretibial
dermopathy (Graves' disease)
Pale, cool, puffy skin; dry and brittle hair; brittle nails
Eyes, face Retraction of upper lid with wide
stare; periorbital edema;
exophthalmos; diplopia
(Graves' disease)
Drooping of eyelids; periorbital
edema; loss of temporal aspects
of eyebrows; puffy, nonpitting
facies; large tongue
Cardiovascular
system
Decreased peripheral vascular
resistance, increased heart rate,
stroke volume, cardiac output,
pulse pressure; high-outputheart failure; increased
inotropic and chronotropic
effects; arrhythmias; angina
Increased peripheral vascular
resistance; decreased heart rate,
stroke volume, cardiac output,
pulse pressure; low-output heartfailure; ECG: bradycardia,
prolonged PR interval, flat T
wave, low voltage; pericardial
effusion
Respiratory system Dyspnea; decreased vital capacity Pleural effusions; hypoventilation
and CO2 retention
Manifestations of thyrotoxicosis and hypothyroidism (1)
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Manifestations of thyrotoxicosis and hypothyroidism (2)
Gastrointestinal
system
Increased appetite; increased
frequency of bowel
movements; hypoproteinemia
Decreased appetite; decreased
frequency of bowel
movements; ascites
Central nervous
system
Nervousness; hyperkinesia;
emotional lability
Lethargy; general slowing of
mental processes; neuropathies
Musculoskeletal
system
Weakness and muscle fatigue;
increased deep tendon
reflexes; hypercalcemia;osteoporosis
Stiffness and muscle fatigue;
decreased deep tendon reflexes;
increased alkaline phosphatase,LDH, AST
Renal system Mild polyuria; increased renal
blood flow; increased
glomerular filtration rate
Impaired water excretion;
decreased renal blood flow;
decreased glomerular filtration
rate
Hematopoietic
system
Increased erythropoiesis; anemia1 Decreased erythropoiesis; anemia1
Reproductive system Menstrual irregularities; decreased
fertility; increased gonadal
steroid metabolism
Hypermenorrhea; infertility;
decreased libido; impotence;
oligospermia; decreased
gonadal steroid metabolism
System Thyrotoxicosis Hypothyroidism
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Metabolic system Increased basal metabolic
rate; negative nitrogen
balance; hyperglycemia;
increased free fatty acids;
decreased cholesterol and
triglycerides; increased
hormone degradation;
increased requirements for
fat- and water-soluble
vitamins; increased drugmetabolism
Decreased basal metabolic
rate; slight positive
nitrogen balance; delayed
degradation of insulin, with
increased sensitivity;
increased cholesterol and
triglycerides; decreased
hormone degradation;
decreased requirements for
fat- and water-solublevitamins; decreased drug
metabolism
Manifestations of thyrotoxicosis and hypothyroidism (3)
System Thyrotoxicosis Hypothyroidism
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hyposecretion of T3 & T4
myxedema
After thyroid
treatment
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hyposecretionof T3 & T4
Cretinism
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Goiter
Lack of iodine in diet
hyposecretion of T3 & T4
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PTH release:
1) stimulates osteoclasts2) enhances reabsorption of Ca++ by kidneys
3) increases absorption of Ca++ by intestinal
mucosal cells
Hyperparathyroidism- too much Ca++ drawn out of
bone; could be due to tumor
Hypoparathyroidism- most often follow parathyroidgland trauma or after removal of thyroid--- tetany,
muscle twitches, convulsions; if
untreatedrespiratory paralysis and death
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u
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Figure 18 15
uCalcium Ion Concentrations