| Discovery | This is a thyrotropic glycoprotein hormone secreted from
the anterior pituitary. TSH stimulates thyroid growth and
function as well as thyroid hormone secretion. Bovine TSH was the first purified TSH, and its primary
structure was determined in 1971. The structure and full
nucleotide sequence of the human TSH β-subunit gene
was determined in 1985. |
| Structure | TSH is a glycoprotein consisting of noncovalently
linked glycoprotein hormone (GPH) α- and TSH
β-subunits. The GPH α-subunit is common to the
follicle-stimulating hormone (FSH), luteinizing hormone
(LH), and chorionic gonadotropin (CG) . The TSH β-subunit contains a
cysteine-knot motif, which is critical for the heterodimer
assembly and its biological activity. The N-linked oligosaccharide chain is important for the intracellular folding,
secretion, metabolic clearance, and biological activity of
the hormone. Mr 25,000–30,000, pI 6.8–8.5. Multiple isoforms exist
due to the microheterogeneity of oligosaccharide chains.
Soluble in water. Inactivated by heating; treatment with
trypsin, chymotrypsin, and pepsin; and oxidation (potassium permanganate, elemental iodine). |
| Synthesis and release | The synthesis and release of TSH are directly stimulated by thyrotropin-releasing hormone (TRH). The
administration of estrogen and insulin, and cold exposure, have stimulatory effects on TSH release. Thyroid
hormones (T3 and T4) inhibit the synthesis and release
of TSH through binding to the thyroid hormone receptor.
Somatostatin and melanin-concentrating hormone
(MCH) also inhibit TSH release. In the pars tuberalis,
TSH secretion is regulated by melatonin that transmits
photoperiodic information to regulate seasonal reproduction in mammals. |
| Receptors | The receptor of TSH (TSHR) is a glycoprotein that
belongs to a subclass of the rhodopsin/β-adrenergic subfamily of the membrane-bound GPCR superfamily. The
TSHR consists of around 770 aa residues containing a
large N-terminal extracellular domain (~410 aa residues),
seven transmembrane domains, and a C-terminal intracellular domain. TSHR is mainly coupled to Gs and Gq proteins, and
TSH activates the cAMP and PLC cascades. |
| Agonist and antagonists | Recombinant human TSH and small molecule TSHR
ligands are agonists. Deglycosylated TSH7 and small molecule TSHR antagonist are antagonists. |
| Gene, mRNA, and precursor | The human TSH β-subunit gene, TSHB, location 1p13,
consists of three exons. Human TSH
β-subunit mRNA has 867 b that encode a signal peptide
of 19 aa residues and a mature protein of 119 aa residues. The TSH β-subunit mRNA is present in the basophilic
thyrotropes distributed in the pars distalis and pars
tuberalis of the anterior pituitary. |
| Biological functions | TSH derived from the pars distalis of the pituitary
binds to the TSHR located on the membrane of thyroid
follicular cells. TSH stimulates thyroid hormone production, iodine uptake and organification, and thyroid
growth. TSH derived from the pars tuberalis of the pituitary binds to the TSHR in the ependymal cells and
induces the expression of type 2 deiodinase (Dio2), which
converts T4 into bioactive T3. This leads to seasonal reproduction. TSHR is also expressed in a variety of extrathyroidal tissues including fat, fibroblasts, bone, and
cardiomyocytes. |
| Clinical implications | Familial TSH deficiency with point mutations in
TSHB and numerous mutations in the TSHR gene
have been identified and associated with thyroid diseases. Graves’ disease is an autoimmune thyroid disorder in which the body produces antibodies to TSHR
(TSAbs) that mimic the effects of TSH. TSAbs induce
increased metabolic rate, and the associated symptoms
result in thyroid eye disease, exophthalmos (protuberance of one or both eyes), fatigue, weight loss with
increased appetite, and other symptoms of
hyperthyroidism. |
| Uses | Thyrogen (Genzyme). |
| Uses | Thyrotropic hormone from porcine pituitary can be used as a NCTC-135 medium supplement for isolating the thyroid cells which in turn is used for studying the impact of retinoids on non-transformed cells like thyrocytes. The product can also be used in cell proliferation experiment for studying the impact of increased IGF binding proteins 1 level on the function and growth of the thyroid gland in transgenic mice. |
| Definition | A hormone secreted by the anterior lobe of the pituitary gland. It increases the rate of removal of iodine from the blood by the thyroid gland, synthesis of the thyroid hormone, and its release into the bloodstream. The thyrotropic hormone is a protein with a low molecular weight (about 10,000) that contains some carbohydrate.
|
| Indications | TSH, or thyrotropin, is a glycosylated protein of two
subunits, and . TSH stimulates the thyroid gland to
produce thyroid hormones. Deficiencies are treated by
giving thyroxine itself rather than TSH, but TSH is
available for diagnostic purposes to differentiate between
pituitary and thyroid gland failure as causes of
hypothyroidism. |
| Brand name | Thyrotrophin is INN and BAN. |
| General Description | The thyrotropic hormone, also called thyrotropin and thyroidstimulatinghormone (TSH), is a glycoprotein consisting oftwo polypeptide chains. This hormone promotes productionof thyroid hormones by affecting the kinetics of the mechanismby which the thyroid concentrates iodide ions from thebloodstream, thereby promoting incorporation of the halogeninto the thyroid hormones and release of hormones by thethyroid.
TSH (Thyropar) appears to be a glycoprotein (relativemolecular mass [Mr] 26,000–30,000) containing glucosamine,galactosamine, mannose, and fucose, whose homogeneityis yet to be established. It is produced by thebasophil cells of the anterior lobe of the pituitary gland.TSH enters the circulation from the pituitary, presumablytraversing cell membranes in the process. After exogenousadministration, it is widely distributed and disappears veryrapidly from circulation. Some evidence suggests that thethyroid may directly inactivate some of the TSH by an oxidationmechanism that may involve iodine. TSH thus inactivatedcan be reactivated by certain reducing agents.TSH regulates the production by the thyroid gland of thyroxine,which stimulates the metabolic rate. Thyroxinefeedback mechanisms regulate the production of TSH bythe pituitary gland. |
| Biochem/physiol Actions | Two-chain glycoprotein hormone. The α-chain is not active, biological specificity attributed rather to the β-chain. Activates adenylate cyclase in the thyroid gland, stimulating iodine uptake, thyroxine synthesis and release. Goitrogenic. |
| Clinical Use | Recombinant form of human thyroidstimulating hormone (rhTSH). Used
diagnostically for serum thyroglobulin
testing. |
| Clinical Use | TSH levels are measured as part of a thyroid function
test in patients suspected of hyperthyroidism and hypothyroidism as the simplest and most sensitive indicator.
Primary hypothyroidism/hypothyroidism is characterized by a high/low serum TSH concentration and a
low/high serum free T4 concentration. Subclinical
hypothyroidism/hypothyroidism is defined biochemically as a normal free T4 concentration in the presence
of an increased/decreased TSH concentration. Central
hypothyroidism is characterized by a low serum T4 concentration and a low or normal serum TSH concentration,
whereas TSH-secreting pituitary adenomas may lead to the development of hyperthyroidism through a condition
called the syndrome of the inappropriate secretion of TSH
(SITSH). Recombinant human TSH is used in the follow up of patients with thyroid cancer to ablate the thyroid
remnant following thyroid cancer surgery, and to obtain
reliable diagnostic test results for the recurrence of differentiated thyroid cancer. |
| Veterinary Drugs and Treatments | The labeled indications for the formerly available veterinary product
Dermathycin? (Mallinckrodt) was for “the treatment of acanthosis
nigricans and for temporary supportive therapy in hypothyroidism
in dogs.” In actuality however, TSH is used in veterinary
medicine principally as a diagnostic agent in the TSH stimulation
test to diagnose primary hypothyroidism. |
