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    Thyroid Hormones

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    chayChay gapol
    The document discusses thyroid hormones, including their biosynthesis, secretion, regulation, and physiological functions. Key points include: - Thyroid hormones T4 and T3 are synthesized from iodine transported into thyroid follicular cells and incorporated into thyroglobulin. - T4 makes up 93% of secreted hormones while T3 is more potent but comprises only 7% of secretion. - Secretion of thyroid hormones is regulated by TSH through a negative feedback loop. - Thyroid hormones have important roles in development and metabolism and both hypo- and hyperthyroidism can have clinical consequences.

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    Thyroid Hormones

    Uploaded by

    chayChay gapol
    20 views38 pages
    The document discusses thyroid hormones, including their biosynthesis, secretion, regulation, and physiological functions. Key points include: - Thyroid hormones T4 and T3 are synthesized from iodine transported into thyroid follicular cells and incorporated into thyroglobulin. - T4 makes up 93% of secreted hormones while T3 is more potent but comprises only 7% of secretion. - Secretion of thyroid hormones is regulated by TSH through a negative feedback loop. - Thyroid hormones have important roles in development and metabolism and both hypo- and hyperthyroidism can have clinical consequences.

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    The document discusses thyroid hormones, including their biosynthesis, secretion, regulation, and physiological functions. Key points include: - Thyroid hormones T4 and T3 are synthesized from iodine transported into thyroid follicular cells and incorporated into thyroglobulin. - T4 makes up 93% of secreted hormones while T3 is more potent but comprises only 7% of secretion. - Secretion of thyroid hormones is regulated by TSH through a negative feedback loop. - Thyroid hormones have important roles in development and metabolism and both hypo- and hyperthyroidism can have clinical consequences.

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    20 views38 pages

    Thyroid Hormones

    Uploaded by

    chayChay gapol
    The document discusses thyroid hormones, including their biosynthesis, secretion, regulation, and physiological functions. Key points include: - Thyroid hormones T4 and T3 are synthesized from iodine transported into thyroid follicular cells and incorporated into thyroglobulin. - T4 makes up 93% of secreted hormones while T3 is more potent but comprises only 7% of secretion. - Secretion of thyroid hormones is regulated by TSH through a negative feedback loop. - Thyroid hormones have important roles in development and metabolism and both hypo- and hyperthyroidism can have clinical consequences.

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    THYROID

    HORMONES
    LEARNING OBJECTIVES
    ▪ At the end of this lecture, you should be able to:
    ▪ Identify the steps in the biosynthesis, storage, and secretion of thyroid hormones
    and their regulation.
    ▪ Describe factors that control the synthesis, storage, and release of thyroid
    hormones.
    ▪ Explain the importance of thyroid hormone binding in blood on free and total
    thyroid hormone levels.
    ▪ Describe the actions of thyroid hormones on development and metabolism.
    ▪ Understand the causes and consequences of a) over-secretion and b)
    under-secretion of thyroid hormones.
    THYROID GLAND
    ▪ immediately below the larynx on each
    side of and anterior to the trachea
    ▪ one of the largest endocrine glands
    ▪ 15 to 20 grams
    ▪ thyroxine and triiodothyronine (T3, T4).
    calcitonin
    ▪ secretion is controlled primarily by
    thyroid stimulating hormone (TSH)
    SYNTHESIS AND SECRETION
    ▪ 93% T4, 7% T3 (4x more potent)
    ▪ T4 conversion in tissues
    ▪ T3:
    ▪ Short half life
    ▪ Smaller quantities
    PHYSIOLOGICAL ANATOMY
    ▪ Follicles
    ▪ Colloid
    ▪ Cuboidal epithelial cells
    ▪ Thyroglobulin
    ▪ blood flow about 5x the weight
    of the gland each minute
    ▪ C cells that secrete calcitonin
    SYNTHESIS OF THYROID
    HORMONE
    ▪ Iodide transport
    ▪ Thyroglobulin synthesis
    ▪ Oxidation of I– to I°
    ▪ Iodination
    ▪ Coupling
    ▪ Storage of thyroid hormones
    IODIDE TRANSPORT
    ▪ 50 milligrams/year or 1 mg/week
    ▪ common table salt- iodized with about 1 part sodium
    iodide to every 100,000 parts sodium chloride
    ▪ Iodine uptake via a sodium/potassium pump powered
    sodium/iodide symporter on the basal membrane (NIS)
    ▪ Blocked by: perchlorate and thiocyanate (compete with I)
    ▪ I¯ is transported into the lumen by an anion exchanger
    called pendrin
    THYROGLOBULIN SYNTHESIS
    ▪ high molecular weight protein (>300,000 daltons)
    ▪ synthesized in ribosomes, glycosylated in the
    endoplasmic reticulum, packaged into vesicles in the
    Golgi apparatus
    ▪ thyroglobubin then enters the lumen via exocytosis
    OXIDATION OF I– TO I°
    ▪ thyroperoxidase (TPO)
    ▪ located at the apical border of the follicle cell, catalyzes
    oxidation
    ▪ catalyzes iodination and coupling
    IODINATION
    ▪ (<20%) of thyroglobulin
    tyrosine residues are
    iodinated
    ▪ Peroxidase
    ▪ Initial products: mono- and
    diiodotyrosine (MIT and
    DIT)
    COUPLING
    ▪ Peroxidase also promotes the coupling of iodinated
    tyrosine in the thyroglobulin Molecule
    ▪ two DITs couple, tetraiodothyronine (T4)
    ▪ one DIT and one MIT combine, triiodothyronine (T3)
    ▪ When iodine is abundant, mainly T4 is formed
    ▪ odine becomes scarce, the production of T3 increases
    STORAGE OF THYROID
    HORMONES
    ▪ stored as iodinated thyroglobulin in the follicular colloid
    to last the body for 2–3 months
    SECRETION OF THYROID
    HORMONE
    ▪ Pinocytosis: Pieces of the
    follicular colloid are taken
    back into the follicle by
    endocytosis.
    ▪ Fusion: The endocytosed
    material fuses with lysosomes,
    which transport it toward the
    basal surface of the cell.
    SECRETION OF THYROID
    HORMONE
    ▪ Proteolysis of thyroglobulin:
    Within the lysosomes, the
    thyroglobulin is broken into
    free amino acids, some of
    which are T4, T3, DIT, and
    MIT.
    SECRETION OF THYROID
    HORMONE
    ▪ Secretion: T4 and T3 are
    secreted into the blood, with
    the T4:T3 ratio being as high
    as 20:1. The thyroid has the
    same 5’-mono-deiodinase
    found in many peripheral
    tissues and in an
    iodine-deficient state more
    of the hormone can be
    released as T3.
    SECRETION OF THYROID
    HORMONE
    ▪ Deiodination: A microsomal
    deiodinase removes the
    iodine from iodinated
    tyrosines (DIT and MIT) but
    not from the iodinated
    thyronines (T3 and T4)
    ▪ iodine is then available for
    resynthesis of hormone
    TRANSPORT OF THYROID
    HORMONES IN BLOOD
    ▪ T3 & t4 are bound to plasma proteins
    ▪ combine mainly with thyroxine-binding globulin and
    much less so with thyroxine-binding prealbumin and
    albumin.
    ▪ T4 half-life = 6 days
    ▪ T3 half-life = 1 day
    ▪ Thyroxine and triiodothyronine are released slowly to
    tissue cells
    SEATWORK
    ▪Identify the different substances that
    would inhibit the different steps in
    thyroid hormone synthesis.
    PHYSIOLOGICAL
    FUNCTIONS
    OF THE THYROID
    HORMONES
    CONTROL OF THYROID
    HORMONE SECRETION
    ▪ TRH provides a constant and
    necessary
    ▪ absence of TRH - secretion of
    TSH (and T4) decreases to
    very low levels
    ▪ TSH targets the thyroid
    CONTROL OF THYROID
    HORMONE SECRETION
    ▪ Negative feedback of thyroid
    hormones is exerted mainly at
    the level of the anterior
    pituitary gland.
    ▪ T4 that is responsible for most
    of the negative feedback.
    CONTROL OF THYROID
    HORMONE SECRETION
    ▪ within the thyrotrophs the T4
    is converted to T3 before it
    acts to reduce the sensitivity
    of the thyrotroph to TRH
    CONTROL OF THYROID
    HORMONE SECRETION
    ▪ As long as circulating free T4 remains normal, changes in
    circulating T3 have minimal effects on TSH secretion.
    ▪ TSH secretion increases if there is a significant drop in
    circulating free T4, even in the presence of an increase in
    circulating T3.
    ANTITHYROID SUBSTANCES
    ▪ best known antithyroid drugs:
    ▪ Thiocyanate
    ▪ propylthiouracil
    ▪ high concentrations of inorganic iodides
    DISEASES OF THE
    THYROID
    HYPERTHYROIDISM
    ▪ Toxic Goiter
    ▪ Thyrotoxicosis
    ▪ Graves’ Disease

    ▪ thyroid gland is increased to 2x – 3x normal size


    ▪ tremendous hyperplasia and infolding of the follicular cell
    lining into the follicles,
    ▪ number of cells is increased greatly
    GRAVE’S DISEASE
    ▪ most common form of
    hyperthyroidism
    ▪ autoimmune disease
    ▪ Antibodies called
    thyroid-stimulating
    immunoglobulins (TSIs)
    ▪ Form against the TSH receptor in
    the thyroid gland
    SYMPTOMS OF
    HYPERTHYROIDISM
    ▪ (1) a high state of excitability
    ▪ (2) intolerance to heat
    ▪ (3) increased sweating
    ▪ (4) mild to extreme weight loss (sometimes as much as 100 pounds)
    ▪ (5) varying degrees of diarrhea
    ▪ (6) muscle weakness
    ▪ (7) nervousness or other psychic disorders
    ▪ (8) extreme fatigue but inability to sleep
    ▪ (9) tremor of the hands
    HYPOTHYROIDISM
    ▪ often initiated by autoimmunity against the thyroid gland
    (Hashimoto’s disease)
    ▪ autoimmunity destroys the gland rather than stimulates it
    ▪ thyroid glands of most of these patients first demonstrate
    autoimmune “thyroiditis”
    ▪ progressive deterioration and finally fibrosis of the gland, with
    resultant diminished or absent secretion of thyroid hormone
    MYXEDEMA
    ▪ develops in persons who have
    almost total lack of thyroid
    hormone function
    ▪ greatly increased quantities of
    hyaluronic acid and chondroitin
    sulfate bound with protein form
    excessive tissue gel in the
    interstitial spaces, which causes
    the total quantity of interstitial
    fluid to increase
    CRETENISM
    ▪ extreme hypothyroidism during fetal
    life, infancy, or childhood
    ▪ failure of body growth and by mental
    Retardation
    ▪ results from congenital lack of a
    thyroid gland (congenital cretinism),
    from failure of the thyroid gland to
    produce thyroid hormone because of
    a genetic defect of the gland, or from a
    lack of iodine in the diet (endemic
    cretinism)

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