| Thyrotropic cell | |
|---|---|
| Details | |
| Location | Anterior pituitary |
| Function | Thyroid stimulating hormone secretion |
| Identifiers | |
| MeSH | D052684 |
| TH | H3.08.02.2.00005 |
| Anatomical terms of microanatomy | |
Thyrotropic cells (also called thyrotropes, or thyrotrophs) areendocrine cells in theanterior pituitary which producethyroid-stimulating hormone (TSH) in response tothyrotropin-releasing hormone (TRH) from thehypothalamus.[1] Thyroid-stimulating hormone, or thyrotropin, triggers the release ofthyroxine (T4) andtriiodothyronine (T3) from thethyroid gland.[1] Thyrotropes comprise around 5% of theanterior pituitary lobe cells.[2]
Thyrotropes appearbasophilic inhistological preparations. In the image displayed on the right, thyrotropes are the cells with the bluish-purple cytoplasm and the dark purple nucleus. Normal morphology of these cells is characterized by a round shape. However, these cells are best displayed under light microscopy performed followingimmunohistochemistry with TSH. This specific type of imaging allows for the visualization of the location of thyrotrophs in the anterior pituitary gland. Thyrotropic cells are clustered together in the anteromedial region of the gland.[3]
Thyrotrophs can be identified via immunocytochemistry as early as the 12th week of fetal development, roughly at the same time thatgonadotrophs can be detected. The active hormone, TSH, is detected at the 14th week ofgestation. Transcription factors, such asPit-1,GATA-2, and PROP1, influence cell proliferation and maturation.[3]
Thehypothalamus secretesthyrotropin-releasing hormone (TRH) into portal veins, which carry this hormone to the anterior pituitary. Thyrotropin-releasing hormone is a relatively small peptide, containing only three amino acids. TRH stimulates the thyrotropic cells through the use of aphospholipase C second messenger system.[1] TRH binds to a class AG protein-coupled receptor on the surface of a thyrotropic cell, which is known as thethyrotropin-releasing hormone receptor (TRHR). Strong hydrogen bonding interactions stabilize the binding of TRH to TRHR. This binding event induces the coupling of Gαq/G11, which activates phospholipase C. Phospholipase C cleaves PIP2 into IP3.Inositol-1,4,5-triphosphate (IP3) binds to calcium channels along the membrane of the endoplasmic reticulum causing a conformational change, which opens the channels and subsequently releases Ca2+ ions into the cytosol of the thyrotrophs.[4]
TSH consists of noncovalently associated subunits: an α-subunit that is conserved in other pituitary hormones and a β-subunit that gives the hormone its specificity. These subunits are synthesized from different genes. These subunits are transcribed in response to the signaling of TRH.[5] The direct pathway from the release of calcium ions to the expression of these genes in thyrotropic cells is unknown. The subunits areglycosylated and remodeled as they move through the cell. Further glycosylation of the subunits occurs as they progress through thesecretory pathway.[6] Thyroid stimulating hormone is stored in the secretorygranules of thyrotropic cells. Release of these granules is also induced by the signaling of TRH.[5]
Multiple neurogenic stimuli are known to affect the release of TSH from thyrotropes. Exposure to cold temperatures increases the secretion of TSH. This increased secretion results from the increased secretion of TRH, as the hypothalamus is excited by the change in body temperature.[1] Furthermore, emotions that activate thesympathetic nervous system—such as excitement and anxiety—decrease the secretion of TSH. The decrease in secretion is also connected to the change in body temperature. Activation of the sympathetic nervous system increases the body temperature, which then causes a decrease in TRH secretion and the subsequent decrease in TSH secretion.[1]
Thyroid hormones can have a direct inhibitory effect on thyrotropic cells, though the exact mechanism is unknown. At elevated levels ofthyroxine, the rate of secretion of TSH decreases to near zero, as the body tries to maintain a relatively constant level of thyroid hormone in circulation.[1] However, the inhibitory effect of thyroid hormones may decrease in thyrotropic tumor cells. The receptor affinity for T3 significantly decreases for thyrotropic tumor cells in culture when compared to healthy thyrotropes, which reduces the regulatory effect.[7]
In addition, duringpregnancy, the size of the pituitary gland increases, and consequently, the expression of TSH also increases. This increase in secretion of TSH likely results from the additional metabolic load that pregnant mothers experience in combination with the secretion ofplacental hormones.[1]
GLP-1 can also impact the secretion of TSH, though the exact mechanism is unknown. The presence of high affinitybinding sites for GLP-1 was recently discovered in the thyrotropic cells of rodents. Understanding this pathway can help the formulation of treatments fortype II diabetes mellitus, as there exists a strong association between metabolic diseases and thyroid dysfunction.[8]
This image shows the histology of a thyrotroph tumor. These thyrotroph tumors are referred to as thyrotrophadenomas, and are very rare. They typically present as functionalmacroadenomas and generally appear in individuals in their 50s. Thyrotroph adenomas are not well understood as they only comprise roughly 1% of all pituitary tumors.[9] These tumors typically result in increased secretion of TSH. Individuals with thyrotroph adenomas typically havehyperthyroidism anddiffuse goitre. Diffuse goitre refers to the elongated enlargement of the thyroid gland that results from the increased expression of TSH.[10]
In histological staining, the thyrotropic cells appear more elongated and spindle shaped and are regularly accompanied by fibrosis.[9]
TheWorld Health Organization (WHO) classifies pituitary tumors based on their transcription factors and hormones, as these factors provide insight into the cell lineage and purpose. Thyrotropic adenomas are identified as having the transcription factors,Pit-1, TEF, andGATA-2, and the hormones, β-TSH and α-subunit. Pit-1, in combination with thyrotroph embryonic factor (TEF), contributes to acell's differentiation into a thyrotroph and helps stimulate the production of β-TSH. GATA-2 is a transcription factor for cells that belong to theLhx gene family.[11] Theheterodimer formation between the α-subunit and β-TSH is critical to TSH secretion. Disruption of the α-subunit gene results in a lack of TSH secretion,hypertrophy andhyperplasia of thyrotrophs, and decreased quantities ofsomatotrophs andlactotrophs.[12]
The molecular mechanism behind the formation of these tumors is not well understood, likely due to their low prevalence. Currently, nomutations have been identified in association with thyrotroph adenomas.[9]
In the presence of other pituitary tumors, the thyrotropic cells are unaffected.
In individuals with primaryhyperthyroidism, treatment via thyroid hormone therapy can reverse thehypertrophy andhyperplasia of the thyrotrophs.
Individuals with a rare form ofdwarfism characterized by hypothyroidism lack thyrotropic cells altogether, as this syndrome results from a mutation in the Pit-1 gene.[3]
Excess iodine present in individuals withGraves’ Disease can induce thyrotoxicosis, which is the overexpression of thyroid hormone. Sudden overexpression of the thyroid hormone is referred to asthyroid storm. Thyroid storm results in substantial decreases in the amount of thyrotropic cells in the pituitary gland.[13] This decrease, if significant enough, can be fatal. However, with treatment, this decrease in the number of thyrotrophs can be reversed.[14]
{{citation}}: CS1 maint: work parameter with ISBN (link)