Hormonas Tiroideas

Dr. Victor J. Samillan

A Structural Classification of Hormones

Figure 18.2

larynx thyroid

trachea

The Thyroid Gland

Figure 18.11b, c

Precursor molecule (Tyr) and intermediates (MIT, DIT) during thyroxine 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 follicle cells of thyroid gland

Endocytosis of iodinated thyreoglobulin and

following secretion of T3 and T4 is also upregulated by TSH

Production of TSH is upregulated by TRH and

controled by thyroid hormones via negative feedback

Mechanism of thyroid hormone action

Receptors for thyroid hormones are nuclear and its affinity
is tentimes higher for T3 than T4

The amount of nuclear receptors is very low Four variants of nuclear receptor were observed and
mitochondrial receptor for T3 was also described

Free thyroid hormone receptor (TR) without bound

hormone is bound to hormone response element of DNA (HRE) and corepressor (CoR)

After binding T3 to receptor - CoR is liberated and

coactivators (CoA) is bound and the transcription to mRNA begins

Hormone Effects on Gene Activity

Figure 18.4

Pathways of thyroid hormone metabolism

Thyrotropin-releasing hormone (TRH) increases the secretion of thyrotropin (TSH), which stimulates the synthesis and secretion of trioiodothyronine (T3) and thyroxine (T4) by the thyroid gland. T3 and T4 inhibit the secretion of TSH, both directly and indirectly by suppressing the release of TRH. T4 is converted to T3 in the liver and many other tissues by the action of T4 monodeiodinases. Some T4 and T3 is conjugated with glucuronide and sulfate in the liver, excreted in the bile, and partially hydrolyzed in the intestine. Some T4 and T3 formed in the intestine may be reabsorbed. Drug interactions may occur at any of these sites.

Mechanisms increasing body temperature during hyperthyroidism

Reducing 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 in mitochondria

Increased respiration during hyperthyroidism

Increased synthesis of ATP increased synthesis of cytochrome c oxidase increased oxidative phosphorylation (it means the increased consumption of 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 main
component of glycerol 3-phosphate shuttle in mitochondria (one of transport systems for NADH into mitochondria)

Cytochrome c oxidase the complex

mitochondrial enzyme in the electron transport chain (from cytochrome c to oxygen)

ATPases (eg. Ca ATPase of muscle cells) Carbamyl phosphate synthase enzyme of

urea cycle

Growth hormone

Manifestations of thyrotoxicosis and hypothyroidism (1)

System Skin and appendages Thyrotoxicosis Warm, moist skin; sweating; heat intolerance; fine, thin hair; Plummer's nails; pretibial dermopathy (Graves' disease) Retraction of upper lid with wide stare; periorbital edema; exophthalmos; diplopia (Graves' disease) Decreased peripheral vascular resistance, increased heart rate, stroke volume, cardiac output, pulse pressure; high-output heart failure; increased inotropic and chronotropic effects; arrhythmias; angina Dyspnea; decreased vital capacity Hypothyroidism Pale, cool, puffy skin; dry and brittle hair; brittle nails

Eyes, face

Drooping of eyelids; periorbital edema; loss of temporal aspects of eyebrows; puffy, nonpitting facies; large tongue Increased peripheral vascular resistance; decreased heart rate, stroke volume, cardiac output, pulse pressure; low-output heart failure; ECG: bradycardia, prolonged PR interval, flat T wave, low voltage; pericardial effusion Pleural effusions; hypoventilation and CO2 retention

Cardiovascular system

Respiratory system

Manifestations of thyrotoxicosis and hypothyroidism (2)

System
Gastrointestinal system

Thyrotoxicosis
Increased appetite; increased frequency of bowel movements; hypoproteinemia

Hypothyroidism
Decreased appetite; decreased frequency of bowel movements; ascites

Central nervous system

Musculoskeletal system

Nervousness; hyperkinesia; emotional lability

Weakness and muscle fatigue; increased deep tendon reflexes; hypercalcemia; osteoporosis Mild polyuria; increased renal blood flow; increased glomerular filtration rate Increased erythropoiesis; anemia1 Menstrual irregularities; decreased fertility; increased gonadal steroid metabolism

Lethargy; general slowing of mental processes; neuropathies

Stiffness and muscle fatigue; decreased deep tendon reflexes; increased alkaline phosphatase, LDH, AST Impaired water excretion; decreased renal blood flow; decreased glomerular filtration rate Decreased erythropoiesis; anemia1 Hypermenorrhea; infertility; decreased libido; impotence; oligospermia; decreased gonadal steroid metabolism

Renal system

Hematopoietic system Reproductive system

Manifestations of thyrotoxicosis and hypothyroidism (3)

System
Metabolic system

Thyrotoxicosis

Hypothyroidism

Increased basal metabolic Decreased basal metabolic rate; negative nitrogen rate; slight positive balance; hyperglycemia; nitrogen balance; delayed increased free fatty acids; degradation of insulin, with decreased cholesterol and increased sensitivity; triglycerides; increased increased cholesterol and hormone degradation; triglycerides; decreased increased requirements for hormone degradation; fat- and water-soluble decreased requirements for vitamins; increased drug fat- and water-soluble metabolism vitamins; decreased drug metabolism

Myxedema
hyposecretion of T3 & T4

myxedema

After thyroid treatment

Cretinism

hyposecretion of T3 & T4

Goiter
Lack of iodine in diet hyposecretion of T3 & T4

PTH release: 1) stimulates osteoclasts 2) 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 parathyroid gland trauma or after removal of thyroid--- tetany, muscle twitches, convulsions; if untreatedrespiratory paralysis and death

The Homeostatic Regulation of Calcium Ion Concentrations

Figure 18.15