Teoria Hormonas Tiroideas (2)

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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