Body Metabolism: Thyroi Hormones Flashcards
Which thyroid lobe is larger?
Right
What is colloid primarily made up of?
Thyroglobulin
Parafollicular cells
. Located in thyroid gland btw follicles and synthesize calcitonin
Dietary iodine
. Most important source for replenishment of extracellular iodide taken for thyroid hormone synthesis from extracellular fluid
. Usually organic iodine that is converted to iodide in GI tract prior to absorption and entry into ECF
. 20% is removed from extracellular fluid by thyroid gland
. 80% is freely filterable at glomerulus then some is passively reabsorbed and the rest is excreted in urine
Intake of iodide into thyroid
. Transported through Na/I cotransporter (NIS) fueled by Na driving force
. TSH stimulates this
. Most iodide in gland is utilized in thyroid hormone synthesis but some does diffuse back into circulation
. Iodide leaves cell and enters follicular lumen across apical membrane via pendrin protein
NIS blockers
. Thiocyanate and perchlorate
Relationship btw iodide content in thyroid and activity of iodide trap
. Inverse relationship
Thyroglobulin
. Large glycoprotein synthesized by thyroid follicular cells
. Released via exocytosis into colloid
. Contains 100 Tyr residues but only a few are subject to iodination
Thyroid hormone synthesis on thyroglobulin
. Iodide oxidized by thyroid perioxidase (TP) using H2O as substrate
. Thyroglobulin enters follicular lumen via exocytosis and its Tyr react w/ oxidized iodide to attach it to thyroglobulin forming 3-monoiodo-tyrosine (MIT)
. Second iodination forms 3,5-diiodotyrosine (DIT)
. 2 DIT molecules then oxidatively coupled by TP to form iodothyronine/thyroxine (T4)
. MIT and DIT coupling on thyroglobulin form T3 but it is small amt
. T3 and T4 remain attached to thyrglobulin during this
What stimulates thyroid peroxidase?
. Stimulates by TSH
Thyroid synthesis relationship w/ extracellular iodide
. Biphasic relationship
. Wolf-Chaikoff effect
. At low to moderate levels of extracellular iodide the synthesis of thyroid hormone is stimulated
. At high levels of extracellular iodide the synthesis of thyroid hormone is inhibited
. Mechanism involves inhibition of H2O generation by iodinated lipid derivative iodohexadecanal
Thyroid hormone storage
. Stores a large amt of hormone that slowly turns over
. T3 and 4 remain attached to thyroglobulin in colloid until secretion bc iodide cannot be stored as free anion
. Per molecule thyroglobulin: 7 MIT, 6 DIT, 2 T4, and 0.2 T3
. Once thyroglobulin is iodinated, it is stored in follicles lumen as colloid
Secretion of thyroid hormone
. Membrane- bound protein receptor megalin mediates thyroglobulin uptake through endocytosis
. Expression of megalin and its insertion in apical face of follicular cells is TSH-dependent
. Thyroglobulin-containing colloid droplet is moved towards the basal membrane of follicular cell by microtubules and micofilaments
. At same time lysosomes migrate to fuse w/ colloid droplets and T4 and 3 are released to diffuse out of cell into capillary
. Iodide is removed from MIT and DIT and 50% is recycled while rest leaks back into ECF
T/F thyroglobulin is not secreted from gland
T
T3 synthesis outside of thyroid gland
. 80% from de-iodination of T4 mostly in liver
. 5’-deiodinase (D1 or D2) removes iodine from 5’ position on outer ring of T4 to produce T3
.
Is there any T4 formed outside of thyroid gland?
No
How many times more potent is T3 over T4?
10 times more potent
Types of 5’-deiodinase
D1: liver, kidneys, and thyroid
. D2: CNS and placenta
. D3: peripheral tissues
Reverse T3
. 5’-deiodinase can remove iodine from 5 position of inner ring to produce this
. Has no biological effect
Activity of Type I 5’-deiodinase can be dec. ___
. Burns . Trauma . Advanced cancer . Renal failure . MI . Febrile states . Starvation . Administration of high glucocorticoids
Pathological conditions that dec. T3 production continued effect
. Dec. T3 production
. Since 5’-deiodinase catalyze the metabolism of rT3 to T2 the rT3 are consequently inc.
TSH reaction to plasma T3 decrease during pathological conditions that dec. type I 5’-deiodinase
. No compensatory rise
. Type II 5’-deiodinase mediates the conversion of T4 to T3 w/in pituitary and CNS and is NOT affected by pathological conditions
. Local T3 in pituitary remains normal so thyrotrophs see adequate amounts of T3
Thyroid transport
. Most T3 and 4 is attached to proteins produced by liver
. Small amt exists in plasma as free, unbound hormone
Binding proteins for T4
. Thyroxine-binding globulin (TBG, 70%)
. Albumin (10%)
. Thyroxine-binding pre-albumin (TBPA, 20%)
Things that cause inc. TBG
. Pregnancy
. Newborn state
. Oral contraceptives and other estrogen sources
. Infectious and chronic active hepatitis
. Genetically determined
Things that dec. TBG
. Androgens and anabolic steroids . Large dose of glucocorticoids . Chronic liver disease . Severe systemic illness . Active acromegaly . Kidney disease w/ proteinuria . Genetically determined
T3 binding proteins
. TBG 70%
. Albumin 40%
Assessment of thyroid function must consider 2 things:
Degree of protein binding
. Measurement of bound and free hormone in plasma
Half life for T3, T4, and rT3
. T3: 1 day
. T4: 6 days
.rT3: 0.7 days
General functions of thyroid hormones
. Adjusts O2 consumption
. ATP synthesis
. Heat production
. Adjusts these based on heat production, alterations in energy requirements, supply of calories, and temperature of environment
Places thyroid hormone acts on in cell
. Mitochondria: enhance conversion of substrates into metabolic energy
. Plasma membrane: inc. entry of substrates into cell
. Nucleus: induce protein synthesis (mitochondrial respiratory enzymes and metabolic enzymes)
Thermogenic effect of thyroid hormones
. Heat production by inc. metabolism and O2 consumption
. Effect occurs in tissues EXCEPT brain, ant. Pituitary, gonads, and spleen
. Develops after latency period of several hrs to days
. Stimulates Na/K-ATPase that generates ADP to stimulate mitochondrial O2 consumption and heat production
. Stimulate futile cycles of catabolism and anabolism to create heat
. May induce expression fo mitochondrial uncoupling proteins (thermogenin)
. Protein dissociates oxidative phosphorylation from ATP generation so mitochondria produces heat w/o generating ATP
Metabolic effects of thyroid hormones
. Alters metabolism of carbs, far,and protein
. Permissive to metabolism, E, GH, and insulin
. Metabolism of substrate supports prevailing O2 consumption and requirements for heat production
Cardiovascular effects of thyroid hormone
. Modulates adrenergic activity of heart by variety of mechanisms
. Rate of transcription for alpha-myosin, Ca-ATPase, beta-adrenergic receptors, G-proteins and adenylyl cyclase
. Net effect: inc. HR, SV, and CO
. Blood flow and O2 delivery to tissues is inc.
. Excessive thyroid hormone can be treated by beta-blockers (propranolol)
Respiration effects of thyroid hormone
. Augments O2 supply and CO2 removal by inc. the rate of ventilation
. Thyroid hormone inc. O2 carrying capacity of blood by enhancing RBC production
Effects of thyroid hormone on brain
. Does not alter metabolic rate
. Essential for normal system development
Effect of thyroid hormone on growth
. Permissive for growth hormone to exert its biological effect on target tissues
. Absence of hormone slows growth and development
. Permissive for metabolic effects of hormones that modulate metabolism: E, GH, and insulin
Metabolism of thyroid hormones
. Metabolized via de-iodination
. None of the di-iodothyronines or mono-iodothyronines have biological effects
. Remaining unmetabolized thyroid hormones are excreted through feces
Hypothalamic factors that modulate the release of thyroid hormones
. TSH from pituitary
. TRH and somatostatin from hypothalamus
Most important physiological regulator of thyroid hormone secretion
TSH
TSH
. Belongs to glycoprotein family
. Synthesized by cells in ant. Pituitary
. Enhances all steps in thyroid hormone production in gland
. Modulates the growth of thyroid tissue itself (trophic effect)
Thyroid hormone negative feedback loop
. T3 and T4 inhibit release of TRH and TSH from hypothalamus and ant. Pituitary
. Dec. in TSH diminished thyroid hormone secretion
. T3 acts on ant. Pituitary to inhibit TRH receptor synthesis and reduce receptor sensitivity
Thyroid hormone levels w/ primary hypersecretion of thyroid hormones by thyroid gland
. Inc. T3 and 4
. Dec. TRH and TSH
Thyroid hormone levels w/ primary hypersecretion of TSH
. Inc. TSH, T3 and 4
. Dec. TRH
Thyroid hormone levels w/ inability of thyroid gland to synthesize hormones
. Dec. T3 and 4
. Inc. TRH and TSH
Thyroid hormone levels w/ insufficient secretion of TSH by ant. Pituitary
. Dec. TSH, T3 and 4
. Inc. TRH
Estrogen relationship to thyroid hormones
. Estrogens inc. thyroxine binding globulin conc. In plasma and elevate total serum conc. Of T4 and T3
. Inc. responsiveness of thyrotroph in ant. Pituitary to TRH possibly through inc. in TRH receptors
Age effect on thyroid
. Modify thyroid hormones
. T3 serum levels start to decline at middle age while T4 remains constant
Effect of glucocorticoids on thyroid hormones
. Depress pituitary TSH secretion
Nutritional effects of thyroid hormone
. Starvation or high glucocorticoids dec. T3 generation from T4 and inc. the accumulation of rT3
. Carb lack appears to play a role in these effects since they can be reversed by administration of carbs
Acute Iodine deficiency
. Plasma levels of T4 fall, plasma levels of TSH rise
. Initially plasma levels of T3 maintained in normal range (T3 will decline if iodine deficiency is prolonged
. Inc. in TSH combined w/ iodine deficiency inc. the ratio of MIT to DIT that is formed on thyroglobulin
. Ratio of T3 to T4 that is formed on thyroglobulin also inc.
. Majority of T3 comes from thyroid gland rather than de-iodination of T4
Chronic iodine deficiency
. Inc. levels TSH induce hypertrophy of thyroid cells
. Can lead to goiter
