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Thyroid Gland:

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Thyroid Gland: Location and Structure The largest pure endocrine gland in the body, located in the front of the neck, on the trachea just below to the larynx. – PowerPoint PPT presentation

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Title: Thyroid Gland:


1
Thyroid Gland
  • Location and Structure

2
  • The largest pure endocrine gland in the body,
    located in the front of the neck, on the trachea
    just below to the larynx.
  • Its two lobes are connected by a median tissue
    mass called the isthmus.
  • Internally, it is composed of about 1 million of
    round follicles. The walls of each follice are
    formed by cuboidal and squamous epithelial cells
    called follicle cells, which produce
    thyroglobulin (glycoprotein).

3
  • The lumen of each follicle stores colloid, which
    consists primarily of molecules of thyroglobulin.
  • The follicular epithelium also consists of
    parafollicular cells, a separate population of
    endocrine cells that produce calcitonin, a
    hormone involved in calcium homeostasis.

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Thyroid hormones (THs)
  • The two THs contain iodine and are called
    thyroxin (or T4) and triiodothyronine or (T3).
  • T4 and T3 have a very similar structure as each
    is made up of two tyrosine amino acids linked
    together and either 4 or 3 atoms of iodine,
    respectively.
  • T4 is the main hormone produced by the thyroid
    and T3 has most if not all of biological activity
    as all target tissues rapidly convert T4 to T3.

6
  • Except for the adult brain, spleen, testes, and
    the thyroid gland itself, THs affect all other
    types of cells in the body where they stimulate
    activity of enzymes especially those involved in
    glucose metabolism
  • Increase metabolic rate in target tissues, which
    increases body heat production (calorigenic
    effect).
  • THs also are critically important for normal
    growth and development of skeletal and nervous
    systems and maturation of reproductive system.

7
Synthesis of thyroid hormones
  • Formation and storage of thyroglobulin.
  • This process takes place in follicle cells and
    the final product is packed into vesicles, their
    contents are discharged into the lumen of the
    follicle and become a major part of the colloid.

8
  • Iodide trapping and oxidation to iodine.
  • To produce functional iodinated hormones,
    follicle cells accumulate iodide from the blood.
    A protein pump (iodide trap), located on the
    basal surface of follicle cells, actively
    transports iodide into follicle cells where it is
    oxidized and converted to iodine (I).

9
  • Iodination.
  • Once formed, iodine is attached to tyrosine amino
    acids which are part of the thyroglobulin.
  • Iodination of one tyrosine produces
    monoiodotyrosine (MIT), iodination of two
    tyrosines diiodotyrosine (DIT).

10
  • Coupling.
  • Then enzymes within the colloid link MITs and
    DITs in a highly specific fashion, as a result
    two DITs linked together result in T4 , while
    coupling of MIT and DIT produce T3.

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  • Coupling (cont.)
  • Interactions between two DITs are more frequent
    so more thyroxin.
  • At this point both thyroid hormones are still
    attached to thyroglobulin molecules in the
    colloid.

13
  • Colloid endocytosis.
  • Colloid droplets containing iodinated
    thyroglobulin are taken up by follicle cells by
    endocytosis. These combine with lysosomes to
    form phagolysosomes.

14
  • Cleavage of the hormones for release.
  • Within the phagolysosomes, the hormones are
    cleaved from the thyroglobulin by lysosomal
    enzymes. The free hormones then diffuse through
    the basal membrane out of the follicle cell and
    into the blood stream.

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Transport and regulation of release
  • Most released T4 and T3 immediately bind to
    plasma proteins, of which the most important is
    thyroxin-binding globulin (TBG) produced by the
    liver.
  • Binding proteins protect T4 and T3 from immediate
    degeneration by plasma enzymes, also they allow
    T4 and T3 to reach target tissues, often located
    a significant distance away from the thyroid
    gland.
  • Decreasing blood levels of thyroxin trigger
    release of TSH from the anterior pituitary, which
    stimulates the thyroid gland to produce more
    thyroxin.

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Actual transmission EM
19
Pathology of the thyroid gland function
  • Both hypo- and hyperactivity and of the thyroid
    gland can cause severe metabolic disturbances.
  • In adults, hypothyroidism is referred to as
  • myxedema.
  • Symptoms
  • Low metabolic rate, poor resistance to cold
    temperatures, constipation, dry skin (especially
    facial), puffy eyes, lethargy and mental
    sluggishness.
  • If hypothyroidism results from lack of iodine
    the thyroid gland enlarges to form a goiter.

20
  • Severe hypothyroidism during the fetal
    development and in infants is called cretinism.
  • Symptoms
  • A short disproportionate body, a thick tongue and
    neck, and mental retardation.
  • The condition is preventable by thyroid hormone
    replacement therapy. However, once developmental
    abnormalities and mental retardation appear,
    they are not reversible.

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Hyperthyroidism
  • The most common form of hyperthyroidism is
    Grave's disease, believed to be an autoimmune
    disease.
  • The immune system produces antibodies that mimic
    TSH, which bind to TSH receptors and permanently
    switch them on, resulting in continuous release
    of thyroid hormones.
  • Typical symptoms include metabolic rate,
    sweating, rapid and irregular heartbeat,
    nervousness, and weight loss despite adequate
    food intake.
  • Often, exophthalmos, or protrusion of the
    eyeballs, occurs caused by the edema of tissues
    behind the eyes followed by fibrosis.
  • Treatments include surgical removal of the
    thyroid gland (very difficult due to an extremely
    rich blood supply) or ingestion of radioactive
    iodine (131I), which selectively destroys the
    most active thyroid cells.

23
Hyperthyroidism and Graves Disease
24
Comparative aspects of thyroid function
  • Originally, it is thought that animals secreted
    iodinated proteins as a defense mechanism (panel
    A on fig. 8-3 Norris).
  • Iodinated molecules were secreted from all over
    the body, including the mouth.
  • Iodinated proteins secreted in the mouth were
    ingested and digested. The iodinated tyrosines
    and thyronines were absorbed.

25
  • Eventually, the secretion of iodinated proteins
    was limited to the interior of the mouth (panel
    B).
  • Iodinated proteins are found in a great number of
    species, including molluscs, arthropods and even
    some algae.

26
  • Cells secreting the iodinated proteins started to
    collect together in the base of the mouth (panel
    C).
  • This arrangement is seen in the amphioxus.

27
  • Cells then congregated into open pits in the base
    of the mouth (panel D).
  • Seen in the ammocetes larvae of the lamprey.

28
  • Finally, these pits were internalized and the
    cells began secreting iodinated tyrosines and
    thyronines directly into the blood (panel D).
  • This transformation is observed during the
    metamorphosis of the lamprey larva into the adult
    form.

29
Pituitary control of thyroid function
  • This seems to have evolved much later on.
  • There are no thyrotrophs in the agnathan
    pituitary.
  • Thyrotrophs probably evolved later on, most
    likely from gonadothrophs.
  • This is supported but the similarities in the
    hormone structures between LH, FSH and TSH.
  • In elasmobranchs, thyrotrophs are located
    adjacent to the gonadotrophs.

30
  • Structurally, thyroptophs and gonadotrophs
    resemble one-another closely.
  • TSH, LH, and FSH all feed back negatively on both
    gonadotrophs and thyrotrophs in teleost fishes.
  • This doesnt happen in mammals.
  • Teleostean gonadotropins have no effect on
    mammalian thyrotrophs.

31
  • In non-mammalian vertebrates, there is a strong
    interaction between the PRL axis and the thyroid
    axis.
  • PRL antagonizes the response to thyroid hormones
    in a number of species.
  • In amphibians, TRH does not seem to regulate TSH
    secretion.
  • Rather, it appears to stimulate PRL secretion.
  • TRH levels are relatively high in the amphibian
    brain.

32
  • Agnathan fishes
  • No true thyroid gland has been identified.
  • However, there are follicle-like structures that
    concentrate iodine.
  • Thyroid hormones have been detected.
  • No definitive functions have been ascribed to the
    thyroid hormones.
  • However, T4 levels have been shown to decrease
    sharply in lampreys when the free-swimming,
    filter-feeding larva metamorphoses into the
    parasitic adult.
  • Iodinated glycoproteins have been suggested to
    play a similar role in metamorphosis in some
    inverts (e.g.. Cnidarians)

33
  • Chondricthyan fishes
  • Very little is known about thyroid function in
    sharks and rays.
  • However, they do have a well developed
    pituitary-thyroid axis.
  • Distinct thyroid hormones are found.
  • There are distinct thyroid cycles which coincide
    with the reproductive cycle.
  • TH thought to be involved in promoting gonadal
    maturation.
  • Thought to be involved in regulating metabolism
    during migration.
  • In at least one species, increased TH induces
    migration.

34
  • Elevated TH levels seem to induce elevated O2
    consumption during embryological development, but
    the response is lost later in development.
  • A number of inconclusive studies have attempted
    to show positive TH control of O2 consumption,
    but conclusive results have been elusive.
  • However, another developmental role for TH has
    been identified.
  • Development of neurosecretory activity in the
    hypothalamus is accelerated by treatment with T3
    and T4 in the oviparous dogfish.

35
  • Chondrostean fishes (sturgeons)
  • Preliminary evidence suggests that circulating TH
    levels peak during spawning behaviour.
  • These elevated levels may also be associated with
    migration.
  • Injection of TH can reverse the gonadal
    degeneration seen in captive sturgeon.
  • This suggests a direct link between thyroid
    activity and reproduction, but further studies
    need to be done.

36
  • Teleost fishes
  • Thyroid tissue is found in diffusely distributed
    follicles, spread throughout the head region
    (fig. 8-6).
  • TRH and somatostatin are found in the
    hypothalamus and appear to have the normal
    functional effects on thyroid hormone secretion.
  • Exception is the salmonid fishes where TRH seems
    to function as an inhibitory neurohormone.
  • T3 is the primary form that is secreted (unlike
    mammals).
  • Thyroid hormone seems to be involved in salt
    water adaptation, regulation of migratory
    behaviour, and metamorphosis (in fish with a
    distinct larval stage).

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  • Sarcopterygean fishes
  • T3 is involved in survival through a drought.
  • During aestivation, the metabolism all but stops
    and water is conserved.
  • During water deprivation, T3 levels drop
    significantly.
  • When water is provided, T3 levels rise and
    metabolic rate increases.

41
  • Amphibians
  • Both T3 and T4 are present.
  • Both are involved in regulation of reproduction
    and metamorphosis.
  • Both regulate moulting and general growth.
  • During metamorphosis, TH influences gene activity
    in the metamorphosing tissue.
  • T3 stimulates apoptosis in the tails of anurans.
  • T3 is also involved in modulating the water drive
    seen in newts.

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  • Thyroid function in reptiles
  • Some reptiles have been shown to have circulating
    MIT and DIT.
  • Isolated thyroid sections secrete MIT and DIT in
    response to TSH in a turtle (Geochemys reevsii),
    a gecko (Geckko gecko), and a snake (Elapha
    rachiata).
  • There are 5 major roles for thyroid hormones in
    the reptiles.

49
  • Reproduction
  • Thyroid function is positively correlated with a
    number of reproductive events in lizards and
    turtles.
  • Elevated thyroid activity (as assessed by
    histological evaluation) is associated with
    spermatogenesis, ovulation, and mating in a
    number of lizard species, as well as at least one
    turtle and one snake species.
  • In the lizard Lacerta vivipara thyroidectomy
    causes premature ejection of most eggs and the
    remaining retained eggs fail to develop.
  • However, there is no evidence that thyroid
    function is associated with gestation in live
    bearing lizards.

50
  • Temperature selection
  • In snakes, thyroid function is greatest during
    warm periods and lowest during hibernation (as
    seen in the common Garter snake.
  • In most temperate lizards, the relationship is
    the same, high in warm seasons and low during
    cold seasons.
  • Artificially changing ambient temperature changes
    thyroid function.

51
  • However, in a number of snakes and lizards, the
    highest level of thyroid function is associated
    with reproduction, not environmental temperature.
  • In lizards from tropical climates, environmental
    temperature does not seem to have any effect on
    thyroid function.
  • Injecting thyroid hormones has been shown to
    cause selection of a warmer temperature.

52
  • Thyroid function and O2 consumption
  • This relationship is temperature-dependent.
  • In animals tested, manipulation of thyroid
    hormones, TSH, or thyroidectomy have little
    effect on O2 consumption at 20oC.
  • However, if temperature is raised to 30oC, then
    O2 consumption is increased by eloevated thyroid
    function.
  • A similar effect is seen on reptile tissues in
    culture at 30oC.

53
  • Moulting
  • Snakes and lizards respond in opposite ways.
  • In lizards, moulting is stimulated by increased
    thyroid hormones and blocked by thyroidectomy.
  • Administration of PRL potentiates the stimulatory
    effect of thyroid hormones.
  • In snakes, the situation is different.
    Thyroidectomy increases the frequency of moulting
    and administration of thyroid hormones stops
    moulting completely.

54
  • Growth
  • Some studies have suggested a possible link
    between thyroid hormones and growth, but very few
    studies have been done in this area.
  • More studies need to be performed before a
    positive correlation can be established.

55
  • Thyroid function in birds
  • The thyroid axis is well developed in birds and
    emerges early in embryonic development.
  • For example, in domestic chickens, the thyroid
    responds to inject TRH by day 6 of development.
  • Plasma levels of thyroid hormones are detectable
    by day 13 and levels rise to a maximum by day 20.

56
  • Thyroid and reproduction.
  • Domestic birds require thyroid for gonadal
    development.
  • T4 is required for testicular development and
    thyroidectomy or administration of goiterogenic
    compounds will induce gonadal regression.
  • However, in many wild species such treatment will
    induce a precocious gonadal development.
  • Probably due to the breeding program for
    domesticated birds.

57
  • Thermogenesis and O2 consumption
  • Thyroid hormones are directly involved in cold
    adaptation.
  • As in mammals, thermogenesis is closely linked to
    O2 consumption.
  • Some wild birds exhibit elevated thyroid function
    during late autumn and winter.
  • Thyroidectomy of adult birds depress their
    ability to generate heat.
  • Treatment with thyroid hormones stimulates O2
    consumption

58
  • Carbohydrate metabolism and growth.
  • Thyroid hormone elevation reduces the glycogen
    stores in the liver, increases plasma free fatty
    acids and causes hyperglycemia.
  • There is evidence to suggest that there is a
    significant interaction between thyroid hormones
    and GH.
  • Release of GH is reduced when thyroid hormones
    are elevated.
  • Thyroidectomy causes depression of growth in
    birds.

59
  • Moulting
  • Thyroids hormones produce stimulatory effects on
    skin and feathers, that are normally thought of
    as being associated with moulting.
  • Moulting is usually regulated along with
    reproduction.
  • Unlike lower vertebrates, thyroid hormones may
    act in a permissive role in mouloting.

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  • Migration
  • Migratory birds seem to have more active thyroid
    glands than non-migratory birds (within and
    between species).
  • May be involved in inducing elevated metabolic
    rates associated with the strenuous act of
    migration.
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