The Thyroid Gland

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The Thyroid Gland

• Felix E. Grissom, Ph.D
• 2219 Adams Bldg
• Howard University
• Tel. [phone]

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Thyroid Gland Hormones and Iodine Metabolism

• C-cells calcitonin (covered later)
• Follicule cells
• Amine hormones
• thyroxine, T1, T2 T3
• ? growth
• ? metabolism
• Thermogenic

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Thyroid Gland Hormones and Iodine Metabolism
Figure 23-7b The thyroid gland
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Thyroxine and its precursors Structure
Synthesis
Figure 23-8 Thyroid hormones are made from
tyrosine and iodine
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Thyroxine and its precursors Structure
Synthesis
Figure 23-9 Thyroid hormone synthesis
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Thyroid HormoneTransport

• T3 T4 leave the thyroid gland by diffusion
• Both are transported in blood by three transport
  proteins, Thyroxine binding globulin (TBG),
  transthyretin and albumin
• A majority (70) of T4 T3 is bound to TBG
• Both enter their target cells by diffusion

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Thyroxine and its precursors Activity

• T4 mainly functions as a prohormone. T3 is the
  main active thyroid hormone and has the highest
  binding affinity for thyroid hormone receptor
  (TR).
• Thyroid hormone activity can be increased in
  plasma without new synthesis by converting T4 to
  T3.
• If too much thyroid activity is present T4 is
  converted to the inactive metabolite rT3 to
  reduce activity.

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Thyroxine and its precursors Activity
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Regulation of thyroid Gland Activity

• Thyroid hormone feedback regulation of gland
  activity via suppression of TRH and TSH secretion
• Autoregulation of thyroid gland activity via the
  Wolfc-Chaikoff Effect
• Energy intake and adipose tissue stores
  regulation of thyroid gland activity via leptin
  and CNS regulation of TRH secretion

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Thyroid Hormone Feedback Regulation

• Hypothalamic TRH stimulates pituitary thyrotrope
  cells to release thyroid stimulating hormone
  (TSH).
• TSH stimulates thyroid epithelial cells to
  release T3 and T4.
• T3 (mainly) stimulates a multitude of cell types
  resulting in the activities exhibited
• T4 T3 feedback to inhibit pituitary
  hypothalamic secretion of TSH and TRH

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Regulation by Energy Intake/Adipose Stores
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T3 T4 Control Pathways Diseases from
Malfunction

• Hypothalamus
• Anterior Pituitary
• Thyroid
• Hypothyroidism
• Goiter (TSH ?)
• Grave's disease

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T3 T4 Control Pathways Diseases from
Malfunction
Figure 23-12 Thyroid hormone pathway
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T3 T4 Control Pathways Diseases from
Malfunction
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Thyroid Gland Summary I

• The thyroid gland is the source of
  tetraiodothyronine T4 and triiodothyronine (T3).
  The basic unit of the thyroid gland is the
  follicle which consists of a single layer of
  epithelial cells surrounding a centrial lumen
  that contains colloid or stored hormone.
• T4 and T3 are synthesized from tyrosine and
  iodide by the enzyme peroxidase. Tyrosine is
  incorporated in peptide linkage within the
  protein thyroglobulin. After iodination, two
  iodotyrosine molecules are coupled to yield
  iodothyronines.
• Secretion of stored T4 T3 requires retrieval of
  thyroglobulin from the follicle lumen by
  endocytosis. To support hormone synthesis,
  Iodine is actively concentrated by the gland and
  conserved within it by recycling the iodotyrosine
  molecules that escape coupling within the
  thyroglobulin.
• Thyrotropin (TSH) acts on the thyroid gland via
  its plasma membrane receptor and cAMP to
  stimulate all steps in the production of T4 T3.
  These steps include iodide uptake, iodination
  and coupling, and retrieval from thyroglobulin.
  TSH also stimulates glucose oxidation, protein
  synthesis, and growth of the thyroid epithelial
  cells. This last effect is partly mediated by
  insulin-like Growth factors.

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Thyroid Gland Summary II

• More than 99.5 of the T4 and T3 circulate bound
  to the protein thyroglobulin (TBG),
  transthyretin, and albumin. Only the free
  fraction of T4 T3 are biologically active.
  Changes in in TBG levels require corresponding
  changes in in thyroid hormone secretion to
  maintain normal concentrations of free T4 T3.
• T4 functions largely as a prohormone.
  Monodeiodination of the outer ring yields 75 of
  the daily production of T3, which is the
  principle active hormone. Alternatively,
  monodeiodination of the inner ring yields reverse
  T3 (rT3), which is biologically inactive.
  Proportioning of T4 between T3 rT3 regulates
  the availability of active hormone.
• T3 and, to a much lesser extent, T4 bind to a
  thyroid hormone receptor (TR) that itself exists
  linked to thyroid regulatory elements (TREs) in
  target DNA molecules. Activation results in
  expression or suppression of the expression of a
  large number of enzymes. As well as structural
  and other functional proteins.
• Thyroid hormone increases and is a major
  regulator of basal metabolic the rate. Oxygen
  utilization is increased by a mechanisms that
  include increases in in the size and number of
  mitochondria, Na,K-ATPase activity, and the rates
  of glucose and fatty acid oxidation and synthesis

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Thyroid Gland Summary III

• Additional important actions of thyroid hormone
  are to increase heart rate, cardiac output, and
  ventilation and to decrease peripheral
  resistance. These actions require the the
  increased tissue oxygen demand. The
  corresponding increase in heat production leads
  to increased sweating. Substrate mobilization
  and disposal of metabolic products are enhanced.
• Other thyroid hormone effects on the central
  central nervous system and skeleton are crucial
  for normal growth and development. With
  children. in the absence the hormone, brain
  development is retarded and cretinism results.
  The stature shortens and the bones fail to
  mature. With adults, thyroid hormone increases
  the rate of bone resorption and the rates of skin
  and hair degradation.
• Hyperthyroidism and hypothyroidism are usually
  easily diagnosed. Both are very amenable to
  therapy.