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The thyroid gland releases the thyroid hormone, which is the body's major metabolic hormone
and found in 2 forms. You have the T4 form also known as thyroxine, which is a major form
consisting of 2 tyrosine molecules and 4 bound iodine atoms. We also have the T3 form or the
triiodothyronine which is going to be a form that has 2 tyrosines and only 3 bound iodine
atoms. This can also be created from T4 by enzymes found at the tissue level. Both are
going to be our iodine-containing amine hormones. The thyroid hormone is a unique hormone
and that it affects virtually every cell in the body. So there are receptors on pretty much
every cell in the body. It enters the target cell and binds to intracellular receptors within the
nucleus of the target cell. It then triggers transcription of various metabolic genes. The
effects of the thyroid hormone can include things such as an increase of the basal metabolic
rate as well as heat production, which we refer to as the calorigenic effect. It also regulates
tissue growth and development and is critical for normal skeletal and nervous system
development and reproductive capacities. The thyroid hormone is also responsible for maintaining
blood pressure and it increases the adrenergic effect in the blood vessels in order to maintain
blood pressure. The thyroid gland stores hormones extracellularly in the follicle lumen until
it is triggered by the thyroid-stimulating hormone to release the thyroid hormones. There are
7 steps involved in the synthesis of thyroid hormone. The first step in the synthesis is the
synthesis of thyroglobulin. Thyroglobulin is synthesized and then discharged into the lumen of
the follicle. Iodide is trapped and from there iodide ions are going to be actively taken into
the cell and then released into the lumen. Iodine is then oxidized when electrons are removed
converting it to iodine. Now that it is in the form of iodine, the iodine is going to be attached
to the tyrosine molecules. This is mediated by peroxidase enzymes and this includes
monoiodotyrosine or MIT, which is going to be formed when only 1 iodine attaches to the
tyrosine. And diiodotyrosine or DIT, which is going to be formed when 2 iodines attach to the
tyrosine. In the next step, these iodinated tyrosines are going to link together to form either
T₃ or T₄. If we have 1 MIT and 1 DIT linked together, then we have T₃ since that's a total of
3 iodines. If 2 DITs linked together, then we get T₄ since that's a total of 4 iodines on these
tyrosine molecules. Next, the colloid is going to be endocytosed by the follicular cells. And
these vesicles then combine with lysosomes. Then within the lysosome, lysosomal enzymes
are going to cleave the T3 and the T4 from the thyroglobulin. Then these hormones are
secreted into the bloodstream where mostly T₄ is secreted but T₃ is also secreted. The T₄ that
is secreted is then converted to T₃ at the tissue level. T₄ and T₃ are transported by proteins
known as thyroxine-binding globulins. Both bind to target receptors, but T₃ is actually
10 times more active than T4 in our body. Our peripheral tissues have enzymes that are
able to convert any T₄ that is available into T₃ and they do this by removing one of the
iodines from T₄ in order to make T₃. The thyroid hormone release is going to be regulated by
negative feedback. Falling thyroid hormone levels is going to stimulate the release of
thyroid-stimulating hormone. Rising thyroid hormone levels then provide a negative feedback
which then inhibits the thyroid-stimulating hormone. Thyroid-stimulating hormone can also
be inhibited by growth hormone-inhibiting hormone as well as dopamine or increased levels of
cortisol and iodide. Hypothalamic thyrotropin-releasing hormone can sometimes overcome
this negative feedback system in cases of things like pregnancy or exposure to cold especially
in infants. The other hormone released by the thyroid is calcitonin. Calcitonin is produced
by the parafollicular cells in response to high blood calcium levels. It is the antagonist to
parathyroid hormone which we will talk about shortly. There is no known physiological role in
humans at normal physiological levels for calcitonin; however, at higher than normal doses
it's going to work to inhibit osteoclast activity in the bone and prevent the release of calcium
from the bone matrix. It also is going to stimulate calcium uptake and incorporation of that
calcium into the bone matrix.