Download Thyroid-stimulating hormone TSH receptor Regulation of thyroid

Thyroid-stimulating hormone
Thyroid-stimulating hormone (also known as thyrotropin,
TSH, or TSH for human TSH) is a pituitary hormone that
stimulates the thyroid gland to produce thyroxine (T4 ), and
then triiodothyronine (T3) which stimulates the metabolism of
almost every tissue in the body.It is a glycoprotein hormone
synthesized and secreted by thyrotrope cells in the anterior
pituitary gland, which regulates the endocrine function of the
thyroid gland.
TSH receptor
The TSH receptor is found mainly on thyroid follicular cells. Stimulation of the
receptor increases T3 and T4 production and secretion. Stimulating antibodies to this
receptor mimic TSH and cause Graves' disease. In addition, hCG shows some crossreactivity to the TSH receptor and therefore can stimulate production of thyroid
hormones. In pregnancy, prolonged high concentrations of hCG can produce a
transient condition termed gestational hyperthyroidism. This is also the mechanism of
trophoblastic tumors increasing the production of thyroid hormones
Regulation of thyroid hormone levels
TSH stimulates the thyroid gland to secrete the hormone thyroxine (T4), which has
only a slight effect on metabolism. T4 is converted to triiodothyronine (T3), which is
the active hormone that stimulates metabolism. About 80% of this conversion is in the
liver and other organs, and 20% in the thyroid itself.TSH is secreted throughout life but
particularly
reaches
high
levels
during
the
periods
of
rapid growth and
development.The hypothalamus, in the base of the brain, produces thyrotropinreleasing hormone (TRH). TRH stimulates the pituitary gland to produce TSH.
Somatostatin is also produced by the hypothalamus, and has an opposite effect on the
pituitary production of TSH, decreasing or inhibiting its release.The concentration of
thyroid hormones (T3 and T4) in the blood regulates the pituitary release of TSH;
when T3 and T4 concentrations are low, the production of TSH is increased, and,
conversely, when T3 and T4 concentrations are high, TSH production is decreased.
This is an example of a negative feedback loop. Any inappropriateness of measured
values, for instance a low-normal TSH together with a low-normal T4 may signal
tertiary disease and a TSH to TRH pathology. Elevated reverse T3 (RT3) together with
low-normal TSH and low-normal T3, T4 values, which is regarded as indicative for
euthyroid sick syndrome, may also have to be investigated for chronic subacute
thyroiditis (SAT) with output of subpotent hormones. Absence of antibodies in patients
with diagnoses of an autoimmune thyroid in their past would always be suspicious for
development to SAT even in the presence of a normal TSH because there is no known
recovery from autoimmunity.
Anti-thyroid Autoantibodies
Thyroid microsomal antibodies were discovered in 1964, which were subsequently
renamed anti-TPO antibodies due to the identification of their autoantigen. Antithyroid autoantibodies (or simply anti-thyroid antibodies) are autoantibodies targeted
against one or more components of the thyroid. The most clinically relevant antithyroid autoantibodies are anti-thyroid peroxidase antibodies (anti-TPO antibodies),
thyrotropin receptor antibodies (TRAbs) and thyroglobulin antibodies. TRAbs are
subdivided into activating, blocking and neutral antibodies, depending on their effect
on the TSH receptor. Graves' disease and Hashimoto's thyroiditis are commonly
associated with the presence of anti-thyroid autoantibodies. Although there is overlap,
anti-TPO antibodies are most commonly associated with Hashimoto's thyroiditis and
activating TRAbs are most commonly associated with Graves' disease. Thyroid
microsomal antibodies were a group of anti-thyroid antibodies, they were renamed
after the identification of their target antigen (TPO).
Anti-thyroid peroxidase (anti-TPO) antibodies are specific for the autoantigen TPO, a
105kDa glycoprotein that catalyses iodine oxidation and thyroglobulin tyrosyl
iodination reactions in the thyroid gland. Most antibodies produced are directed to
conformational epitopes of the immunogenic carboxyl-terminal region of the TPO
protein, although antibodies to linear epitopes have been seen. Anti-TPO antibodies
are the most common anti-thyroid autoantibody, present in approximately 90% of
Hashimoto's thyroiditis, 75% of Graves' disease and 10-20% of nodular goitre or
thyroid carcinoma. Also, 10-15% of normal individuals can have high level anti-TPO
antibody titres. High serum antibodies are found in active phase chronic autoimmune
thyroiditis. Thus, an antibody titer can be used to assess disease activity in patients that
have developed such antibodies.The majority of anti-TPO antibodies are produced by
thyroid infiltrating lymphocytes, with minor contributions from lymph nodes and the
bone marrow. They cause thyroid cell damage by complement activation and antibody
dependent cell cytotoxicity.
Effect on human reproduction
The presence of anti-thyroid antibodies is associated with an increased risk of
unexplained subfertility, miscarriage, recurrent miscarriage, preterm birth and maternal
Postpartum thyroiditis .Activating TSH receptor antibodies were discovered.