Teoria Hormonas Tiroideas (2)

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Hormonas Tiroideas

Dr. Victor J. Samillan



Figure 18.2

Hormones



thyroid

trachea

larynx



The Thyroid Gland

Figure 18.11b,

c



Precursor molecule (Tyr) and

intermediates (MIT, DIT) duringthyroxine biosynthesis



Thyroxine (T4)

3,5,3´,5´-tetraiodothyronine



3,5,3´-triiodothyronine (T3)



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



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



Hormone Effects on Gene

Activity

Figure 18.4



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



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



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



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



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)




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




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





hyposecretion of T3 & T4

myxedema

After thyroid

treatment



hyposecretionof T3 & T4

Cretinism



Goiter

Lack of iodine in diet

hyposecretion of T3 & T4



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



u



Figure 18 15

uCalcium Ion Concentrations

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