Thyrotropic cell

Last updated
Thyrotropic cell
Details
Location Anterior pituitary
Function Thyroid stimulating hormone secretion
Identifiers
MeSH D052684
TH H3.08.02.2.00005
Anatomical terms of microanatomy

Overview

Thyrotropic cells (also called thyrotropes, or thyrotrophs) are endocrine cells in the anterior pituitary which produce thyroid-stimulating hormone (TSH) in response to thyrotropin-releasing hormone (TRH) from the hypothalamus. [1] Thyroid-stimulating hormone, or thyrotropin, triggers the release of thyroxine (T4) and triiodothyronine (T3) from the thyroid gland. [1] Thyrotropes comprise around 5% of the anterior pituitary lobe cells. [2]

Contents

H&E staining of the pituitary gland. Thyrotrophs appear basophilic. Histology of pars distalis of the anterior pituitary with chromophobes, basophils, and acidophils.jpg
H&E staining of the pituitary gland. Thyrotrophs appear basophilic.

Visualization

Thyrotropes appear basophilic in histological 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 following immunohistochemistry 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]

Development

Thyrotrophs can be identified via immunocytochemistry as early as the 12th week of fetal development, roughly at the same time that gonadotrophs can be detected. The active hormone, TSH, is detected at the 14th week of gestation. Transcription factors, such as Pit-1, GATA-2, and PROP1, influence cell proliferation and maturation. [3]

Mechanisms of Stimulation and Secretion

Effect of TRH Signaling

The hypothalamus secretes thyrotropin-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 a phospholipase C second messenger system. [1] TRH binds to a class A G protein-coupled receptor on the surface of a thyrotropic cell, which is known as the thyrotropin-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]

Biosynthesis of Thyroid-Stimulating Hormone (TSH)

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 are glycosylated and remodeled as they move through the cell. Further glycosylation of the subunits occurs as they progress through the secretory pathway. [6] Thyroid stimulating hormone is stored in the secretory granules of thyrotropic cells. Release of these granules is also induced by the signaling of TRH. [5]

Effect of Stimuli on the Release of TSH

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 the sympathetic 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 of thyroxine, 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, during pregnancy, 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 of placental hormones. [1]

GLP-1 can also impact the secretion of TSH, though the exact mechanism is unknown. The presence of high affinity binding sites for GLP-1 was recently discovered in the thyrotropic cells of rodents. Understanding this pathway can help the formulation of treatments for type II diabetes mellitus, as there exists a strong association between metabolic diseases and thyroid dysfunction. [8]

Pathologies associated with Thyrotropic Cells

Thyrotroph Adenomas

H&E staining of a biopsied thyrotroph adenoma. Basophilic cells (thyrotropes) appear spindle-shaped. TSHoma HE.jpg
H&E staining of a biopsied thyrotroph adenoma. Basophilic cells (thyrotropes) appear spindle-shaped.

This image shows the histology of a thyrotroph tumor. These thyrotroph tumors are referred to as thyrotroph adenomas, and are very rare. They typically present as functional macroadenomas 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 have hyperthyroidism and diffuse 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]

The World 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, and GATA-2, and the hormones, β-TSH and α-subunit. Pit-1, in combination with thyrotroph embryonic factor (TEF), contributes to a cell's differentiation into a thyrotroph and helps stimulate the production of β-TSH. GATA-2 is a transcription factor for cells that belong to the Lhx gene family. [11] The heterodimer 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 and hyperplasia of thyrotrophs, and decreased quantities of somatotrophs and lactotrophs. [12]

The molecular mechanism behind the formation of these tumors is not well understood, likely due to their low prevalence. Currently, no mutations have been identified in association with thyrotroph adenomas. [9]

In the presence of other pituitary tumors, the thyrotropic cells are unaffected.

Other Conditions

In individuals with primary hyperthyroidism, treatment via thyroid hormone therapy can reverse the hypertrophy and hyperplasia of the thyrotrophs.

Individuals with a rare form of dwarfism 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 with Graves’ Disease can induce thyrotoxicosis, which is the overexpression of thyroid hormone. Sudden overexpression of the thyroid hormone is referred to as thyroid 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]

See also

Related Research Articles

<span class="mw-page-title-main">Endocrine system</span> Hormone-producing glands of a body

The endocrine system is a messenger system in an organism comprising feedback loops of hormones that are released by internal glands directly into the circulatory system and that target and regulate distant organs. In vertebrates, the hypothalamus is the neural control center for all endocrine systems.

<span class="mw-page-title-main">Thyroid</span> Endocrine gland in the neck; secretes hormones that influence metabolism

The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans, it is a butterfly-shaped gland located in the neck below the Adam's apple. It consists of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the isthmus. Microscopically, the functional unit of the thyroid gland is the spherical thyroid follicle, lined with follicular cells (thyrocytes), and occasional parafollicular cells that surround a lumen containing colloid.

<span class="mw-page-title-main">Thyrotropin-releasing hormone</span> Hormone

Thyrotropin-releasing hormone (TRH) is a hypophysiotropic hormone produced by neurons in the hypothalamus that stimulates the release of thyroid-stimulating hormone (TSH) and prolactin from the anterior pituitary.

Thyroid-stimulating hormone (also known as thyrotropin, thyrotropic hormone, or abbreviated 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 produced by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid.

<span class="mw-page-title-main">Anterior pituitary</span> Anterior lobe of the pituitary gland

The anterior pituitary is a major organ of the endocrine system. The anterior pituitary is the glandular, anterior lobe that together with the makes up the pituitary gland (hypophysis) which, in humans, is located at the base of the brain, protruding off the bottom of the hypothalamus.

<span class="mw-page-title-main">Paraventricular nucleus of hypothalamus</span>

The paraventricular nucleus of hypothalamus is a nucleus in the hypothalamus, that lies next to the third ventricle. Many of its neurons project to the posterior pituitary where they secrete oxytocin, and a smaller amount of vasopressin. Other secretions are corticotropin-releasing hormone (CRH) and thyrotropin-releasing hormone (TRH). CRH and TRH are secreted into the hypophyseal portal system, and target different neurons in the anterior pituitary. Dysfunctions of the PVN can cause hypersomnia in mice. In humans, the dysfunction of the PVN and the other nuclei around it can lead to drowsiness for up to 20 hours per day. The PVN is thought to mediate many diverse functions through different hormones, including osmoregulation, appetite, wakefulness, and the response of the body to stress.

A prolactin cell is a cell in the anterior pituitary which produces prolactin in response to hormonal signals including dopamine, thyrotropin-releasing hormone and estrogen, which are stimulatory. Prolactin is responsible for actions needed for body homeostasis, the development of breasts, and for lactation. The inhibitory effects of dopamine override the stimulatory effects of TRH in non-pregnant, non-lactating sexually mature females. Depending on the sex of the individual, prolactin cells account for 20% - 50% of all cells in the anterior pituitary gland. The inhibitory effects of dopamine override the stimulatory effects of TRH in non-pregnant, non-lactating sexually mature females. Other regulators include oxytocin and progesterone.

<span class="mw-page-title-main">Hypopituitarism</span> Medical condition

Hypopituitarism is the decreased (hypo) secretion of one or more of the eight hormones normally produced by the pituitary gland at the base of the brain. If there is decreased secretion of one specific pituitary hormone, the condition is known as selective hypopituitarism. If there is decreased secretion of most or all pituitary hormones, the term panhypopituitarism is used.

<span class="mw-page-title-main">Thyroid hormone resistance</span> Medical condition

Thyroid hormone resistance (also resistance to thyroid hormone (RTH), and sometimes Refetoff syndrome) describes a rare syndrome in which the thyroid hormone levels are elevated but the thyroid stimulating hormone (TSH) level is not suppressed, or not completely suppressed as would be expected. The first report of the condition appeared in 1967. Essentially this is decreased end organ responsiveness to thyroid hormones. A new term "impaired sensitivity to thyroid hormone" has been suggested in March 2014 by Refetoff et al.

<span class="mw-page-title-main">Endocrine gland</span> Glands of the endocrine system that secrete hormones to blood

The endocrine system is a network of glands and organs located throughout the body. It is similar to the nervous system in that it plays a vital role in controlling and regulating many of the body's functions. Endocrine glands are ductless glands of the endocrine system that secrete their products, hormones, directly into the blood. The major glands of the endocrine system include the pineal gland, pituitary gland, pancreas, ovaries, testicles, thyroid gland, parathyroid gland, hypothalamus and adrenal glands. The hypothalamus and pituitary glands are neuroendocrine organs.

Neuroendocrine cells are cells that receive neuronal input and, as a consequence of this input, release messenger molecules (hormones) into the blood. In this way they bring about an integration between the nervous system and the endocrine system, a process known as neuroendocrine integration. An example of a neuroendocrine cell is a cell of the adrenal medulla, which releases adrenaline to the blood. The adrenal medullary cells are controlled by the sympathetic division of the autonomic nervous system. These cells are modified postganglionic neurons. Autonomic nerve fibers lead directly to them from the central nervous system. The adrenal medullary hormones are kept in vesicles much in the same way neurotransmitters are kept in neuronal vesicles. Hormonal effects can last up to ten times longer than those of neurotransmitters. Sympathetic nerve fiber impulses stimulate the release of adrenal medullary hormones. In this way the sympathetic division of the autonomic nervous system and the medullary secretions function together.

Releasing hormones and inhibiting hormones are hormones whose main purpose is to control the release of other hormones, either by stimulating or inhibiting their release. They are also called liberins and statins (respectively), or releasing factors and inhibiting factors. The principal examples are hypothalamic-pituitary hormones that can be classified from several viewpoints: they are hypothalamic hormones, they are hypophysiotropic hormones, and they are tropic hormones.

<span class="mw-page-title-main">Thyrotropin receptor</span> Mammalian protein found in Homo sapiens

The thyrotropin receptor is a receptor that responds to thyroid-stimulating hormone and stimulates the production of thyroxine (T4) and triiodothyronine (T3). The TSH receptor is a member of the G protein-coupled receptor superfamily of integral membrane proteins and is coupled to the Gs protein.

<span class="mw-page-title-main">Thyrotropin-releasing hormone receptor</span> Protein-coding gene in the species Homo sapiens

Thyrotropin-releasing hormone receptor (TRHR) is a G protein-coupled receptor which binds thyrotropin-releasing hormone.

<span class="mw-page-title-main">Hypothalamic–pituitary–thyroid axis</span> Part of the neuroendocrine system

The hypothalamic–pituitary–thyroid axis is part of the neuroendocrine system responsible for the regulation of metabolism and also responds to stress.

Euthyroid sick syndrome (ESS) is a state of adaptation or dysregulation of thyrotropic feedback control wherein the levels of T3 and/or T4 are abnormal, but the thyroid gland does not appear to be dysfunctional. This condition may result from allostatic responses of hypothalamus-pituitary-thyroid feedback control, dyshomeostatic disorders, drug interferences, and impaired assay characteristics in critical illness.

Hypothalamic–pituitary hormones are hormones that are produced by the hypothalamus and pituitary gland. Although the organs in which they are produced are relatively small, the effects of these hormones cascade throughout the body. They can be classified as a hypothalamic–pituitary axis of which the adrenal, gonadal, thyroid, somatotropic, and prolactin axes are branches.

Hypothalamic disease is a disorder presenting primarily in the hypothalamus, which may be caused by damage resulting from malnutrition, including anorexia and bulimia eating disorders, genetic disorders, radiation, surgery, head trauma, lesion, tumour or other physical injury to the hypothalamus. The hypothalamus is the control center for several endocrine functions. Endocrine systems controlled by the hypothalamus are regulated by antidiuretic hormone (ADH), corticotropin-releasing hormone, gonadotropin-releasing hormone, growth hormone-releasing hormone, oxytocin, all of which are secreted by the hypothalamus. Damage to the hypothalamus may impact any of these hormones and the related endocrine systems. Many of these hypothalamic hormones act on the pituitary gland. Hypothalamic disease therefore affects the functioning of the pituitary and the target organs controlled by the pituitary, including the adrenal glands, ovaries and testes, and the thyroid gland.

Prior to the availability of sensitive TSH assays, thyrotropin releasing hormone or TRH stimulation tests were relied upon for confirming and assessing the degree of suppression in suspected hyperthyroidism. Typically, this stimulation test involves determining basal TSH levels and levels 15 to 30 minutes after an intravenous bolus of TRH. Normally, TSH would rise into the concentration range measurable with less sensitive TSH assays. Third generation TSH assays do not have this limitation and thus TRH stimulation is generally not required when third generation TSH assays are used to assess degree of suppression.

Pulsatile secretion is a biochemical phenomenon observed in a wide variety of cell and tissue types, in which chemical products are secreted in a regular temporal pattern. The most common cellular products observed to be released in this manner are intercellular signaling molecules such as hormones or neurotransmitters. Examples of hormones that are secreted pulsatilely include insulin, thyrotropin, TRH, gonadotropin-releasing hormone (GnRH) and growth hormone (GH). In the nervous system, pulsatility is observed in oscillatory activity from central pattern generators. In the heart, pacemakers are able to work and secrete in a pulsatile manner. A pulsatile secretion pattern is critical to the function of many hormones in order to maintain the delicate homeostatic balance necessary for essential life processes, such as development and reproduction. Variations of the concentration in a certain frequency can be critical to hormone function, as evidenced by the case of GnRH agonists, which cause functional inhibition of the receptor for GnRH due to profound downregulation in response to constant (tonic) stimulation. Pulsatility may function to sensitize target tissues to the hormone of interest and upregulate receptors, leading to improved responses. This heightened response may have served to improve the animal's fitness in its environment and promote its evolutionary retention.

References

  1. 1 2 3 4 5 6 7 Guyton, A.C. & Hall, J.E. (2006) Textbook of Medical Physiology (11th ed.) Philadelphia: Elsevier Saunder ISBN   0-7216-0240-1
  2. ↑ "Costanzo, Linda S. (2014). "Physiology" (5th ed.). Philadelphia: Saunders Elsevier. ISBN 978-1-4557-0847-5
  3. 1 2 3 Werner, Sidney C.; Ingbar, Sidney H.; Braverman, Lewis E.; Utiger, Robert D., eds. (2005). Werner & Ingbar's the thyroid: a fundamental and clinical text, Volume 549 (9th ed.). Philadelphia: Lippincott Williams & Wilkins. pp. 26–35. ISBN   978-0-7817-5047-9.
  4. ↑ Yang, Fan; Zhang, Huanhuan; Meng, Xianyu; Li, Yingge; Zhou, Yingxin; Ling, Shenglong; Sun, Demeng; Lv, Pei; Liu, Lei; Shi, Pan; Tian, Changlin (2022). "Structural insights into thyrotropin-releasing hormone receptor activation by an endogenous peptide agonist or its orally administered analogue". Cell Research. 32 (9): 858–861. doi:10.1038/s41422-022-00646-6. ISSN   1748-7838. PMC   9437008 . PMID   35352031.
  5. 1 2 Sarapura, Virginia D.; Samuel, Mary H. (2017-01-01), Melmed, Shlomo (ed.), "Chapter 6 - Thyroid-Stimulating Hormone", The Pituitary (Fourth Edition), Academic Press, pp. 163–201, doi:10.1016/b978-0-12-804169-7.00006-4, ISBN   978-0-12-804169-7 , retrieved 2024-12-03
  6. ↑ Chin, William W.; Maloof, Farahe; Habener, Joel F. (1981). "Thyroid-stimulating hormone biosynthesis. Cellular processing, assembly, and release of subunits". Journal of Biological Chemistry. 256 (6): 3059–3066. doi: 10.1016/s0021-9258(19)69724-3 . PMID   7204390 – via Elsevier Science Direct.
  7. ↑ Gershengorn, M C; Geras, E; Marcus-Samuels, B E; Rebecchi, M J (1979). "Receptor affinity and biological potency of thyroid hormones in thyrotropic cells". American Journal of Physiology. Endocrinology and Metabolism. 237 (2): E142-6. doi:10.1152/ajpendo.1979.237.2.E142. ISSN   0193-1849. PMID   223453.
  8. ↑ Capuccio, Stefania; Scilletta, Sabrina; La Rocca, Francesca; Miano, Nicoletta; Di Marco, Maurizio; Bosco, Giosiana; Di Giacomo Barbagallo, Francesco; Scicali, Roberto; Piro, Salvatore; Di Pino, Antonino (2024). "Implications of GLP-1 Receptor Agonist on Thyroid Function: A Literature Review of Its Effects on Thyroid Volume, Risk of Cancer, Functionality and TSH Levels". Biomolecules. 14 (6): 687. doi: 10.3390/biom14060687 . ISSN   2218-273X. PMC   11202033 . PMID   38927090.
  9. 1 2 3 Larkin, Sarah; Ansorge, Olaf (2000), Feingold, Kenneth R.; Anawalt, Bradley; Blackman, Marc R.; Boyce, Alison (eds.), "Pathology And Pathogenesis Of Pituitary Adenomas And Other Sellar Lesions", Endotext, South Dartmouth (MA): MDText.com, Inc., PMID   28402620 , retrieved 2024-12-03
  10. ↑ Can, Ahmet S.; Rehman, Anis (2024), "Goiter", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID   32965832 , retrieved 2024-12-03
  11. ↑ Al-Shraim, Mubarak; Asa, Sylvia L. (2006-01-01). "The 2004 World Health Organization classification of pituitary tumors: What is new?". Acta Neuropathologica. 111 (1): 1–7. doi:10.1007/s00401-005-1093-6. ISSN   1432-0533. PMID   16328527.
  12. ↑ Stahl, Justin H.; Kendall, Susan K.; Brinkmeier, Michelle L.; Greco, Tamara L.; Watkins-Chow, Dawn E.; Campos-Barros, Angel; Lloyd, Ricardo V.; Camper, Sally A. (1999-04-01). "Thyroid Hormone Is Essential for Pituitary Somatotropes and Lactotropes*". Endocrinology. 140 (4): 1884–1892. doi:10.1210/endo.140.4.6627. ISSN   0013-7227. PMID   10098528.
  13. ↑ Blick, Carly; Nguyen, Minhthao; Jialal, Ishwarlal (2024), "Thyrotoxicosis", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID   29489233 , retrieved 2024-12-03
  14. ↑ Toro-Tobon, David; Stan, Marius N. (2024-09-24), "Graves' Disease and the Manifestations of Thyrotoxicosis", Endotext [Internet], MDText.com, Inc., PMID   25905422 , retrieved 2024-12-03
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