Mechanism of Thyroid Hormone Action

As previously discussed, the major hormone secreted by the thyroid gland is thyroxine, or tetraiodothyronine (T4). Like steroid hormones, thyroxine travels in the blood attached to carrier proteins (primarily to thyroxine-binding globulin, or TBG). The thyroid also secretes a small amount of triiodothyronine, or T3. The carrier proteins have a higher affinity for T4 than for T3, however, and, as a result, the amount of unbound (or "free") T3 in the plasma is about ten times greater than the amount of free T4.

Approximately 99.96% of the thyroxine in the blood is attached to carrier proteins in the plasma; the rest is free. Only the free thyroxine and T3 can enter target cells; the protein-bound thyroxine serves as a reservoir of this hormone in the blood (this is why it takes a couple of weeks after surgical removal of the thyroid for the symptoms of hypothyroidism to develop). Once the free thyroxine passes into the target cell cytoplasm, it is en-zymatically converted into T3. As previously discussed, it is the T3 rather than T4 that is active within the target cells.

Unlike many of the steroid receptors, the inactive receptor proteins for T3 are located in the nucleus. Until they bind to T3, however, the receptors are incapable of binding to DNA and stimulating transcription. The T3 may enter the cell from the plasma, or it may be produced in the cell by conversion from T4. In either case, it uses some nonspecific binding proteins as "stepping stones" to enter the nucleus, where it binds to the ligand-binding domain of the receptor (fig. 11.6). Once the receptor binds to T3, its DNA-binding domain can attach to the half-site of the DNA hormone-response element.

The other half-site, however, does not bind to another T3 receptor protein. Unlike the steroid hormone receptors, the nuclear receptors in the nonsteroid family bind to DNA as heterodimers. The thyroid hormone receptor (abbreviated TR) is one partner in the heterodimer; the other partner is a receptor (abbreviated RXR) for the vitamin A derivative 9-cis-retinoic acid. Once bound to their different ligands, the two partners in the heterodimer can bind to the DNA to activate the hormone-response element for thyroid hormone (fig. 11.7). In this way, thyroid hormones stimulate transcription of genes, production of specific mRNA, and therefore the production of specific enzymes (see fig. 11.6).

Interestingly, the receptor for 1,25-dihydroxyvitamin D3, the active form of vitamin D, also forms heterodimers with the receptor for 9-cis-retinoic acid (the RXR receptor) when it binds

Mechanisms Hormones Action

RXR receptor

(for 9-cis retinoic acid) -

Blood Target cell

RXR receptor

(for 9-cis retinoic acid) -

Blood Target cell

■ Figure 11.6 The mechanism of action of thyroid hormones on the target cells. T4 is first converted into T3 within the cytoplasm of the target cell. T3 then enters the nucleus and binds to its nuclear receptor. The hormone-receptor complex can then bind to a specific area of DNA and activate specific genes.

to DNA and activates genes. The RXR receptor and its vitamin A derivative ligand thus form a link between the mechanisms of action of thyroid hormone, vitamin A, and vitamin D, along with those of some other molecules that are important regulators of genetic expression.

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Responses

  • Bilcuzal
    What is the name of the target cell that thyroxine attaches to?
    7 years ago
  • gualtiero
    What thyroid hormone can enter its target cells?
    7 years ago
  • luisa esposito
    What is the structure and mode of action of the thyroid hormones T4 and T4 on human receptor cells?
    7 years ago
  • SANDRA EISENBERG
    What is the difference between the mechanism of steroid hormone and thyroid hormone on target cells?
    7 years ago
  • joseph swanson
    Is thyroid mechanism similar to steroid mechanism?
    7 years ago
  • grimalda boffin
    What is the thyroid hormone mechanism steps?
    7 years ago
  • aaron
    What is the mechanism of action of thyroid hormones?
    7 years ago
  • celendine gammidge
    What is the action of thyroid hormones on target cells?
    7 years ago
  • menegilda
    What is the mechanism of thyroid hormone action?
    6 years ago
  • Gundobad
    What is the mode of action of thyroid hormones on target cells?
    6 years ago
  • adonay
    How do thyroid hormones enter the cell?
    6 years ago
  • Aziza
    How thyroid hormones enter.the cells?
    6 years ago
  • Chica
    How thyroid hormones stimulate a responds once entering target cell?
    5 years ago
  • Tove Kuusisto
    What are the diffrent action of t3 and t4 hormones?
    5 years ago
  • PRIMROSE GAUKROGERS
    How does thyroid hormone enters a cell?
    4 years ago
  • JOHANNA
    How thyroid hormone enter in targt cell and bind with receptor?
    3 years ago
  • fosco
    Does throxine enter the cytoplasm?
    3 years ago
  • Mary
    Why thyroid hormone passes into nuclues?
    2 years ago
  • giosu
    How do thyroid cell enter blood cells?
    2 years ago
  • kaj
    Why are the recptors of thyroif horme on the nucleus?
    2 years ago
  • Markus Scherer
    Why does thyroid hormone have its receptor in the nucleus unlike protein hormones?
    2 years ago
  • gregor
    How can thairod acid activate in humon body?
    2 years ago
  • fairy
    What is the mechanism of thyroxine at the target cell?
    2 years ago
  • Makda
    Why triiodo thyroxine enter nucleus?
    2 years ago
  • ralph
    What is the difference between mode of action of hormone and mechanism of horrmones?
    2 years ago
  • ursula
    Where is the thyroid cells nucleus?
    2 years ago
  • tommy
    Why are nuclear receptors affinity ten times higher for t3 tgan t4?
    2 years ago
  • amethyst
    Can T4 directly enter the cell nucleus?
    2 years ago
  • peony
    Why tbg bound t4 enters cells?
    2 years ago
  • Amanda
    How t3 and t4 enter to cells through pumps physiology?
    1 year ago
  • KIRSI M
    What receptor does thyroxine bind to?
    10 months ago
  • Joonas Fr
    How does the thyroxine act on cells and travel in blood?
    8 months ago
  • burtuka
    What does thyroxine share attachment sites with?
    7 months ago
  • Jose
    What happens when t3 and t4 arrive at a target cell human anatomy?
    6 months ago
  • mikko m
    What happens to bone marrow when thyroxine binds to an intracellular receptor?
    5 months ago
  • Sonny
    How does thyroxine get from blood to inside target cell?
    4 months ago
  • STEFAN
    Does thyroxine bind to its receptor in the cytoplasm?
    4 months ago
  • eula
    What are the actions of the thyroid hormones?
    3 months ago
  • kirsi
    How does thyroid hormone remove cell waste?
    3 months ago
  • maximilian
    Which thyroid hormone enters the nucleous?
    3 months ago
  • Wiseman Sackville
    What cells in body use thyroid hormones?
    2 months ago

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