Desensitization, Trafficking, and Resensitization of the Pituitary Thyrotropin-Releasing Hormone Receptor

Hinkle, Patricia M.; Gehret, Austin U.; Jones, Brian W.

doi:10.3389/fnins.2012.00180

Cited by 44 publications

(33 citation statements)

References 120 publications

(185 reference statements)

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“…Under certain physiological conditions, TRH modulates prolactin or growth hormone synthesis and release (Galas et al 2009). The concentration of pituitary TRH-R1 is regulated by TRH and several other hormones (Chiamolera et al 2012, Hinkle et al 2012. Released TSH controls several steps of the synthesis of thyroid hormones (TH) at the thyroid gland, increasing serum levels of thyroxine (T 4 ) and to a minor degree, 3,5,3 0 -triiodothyronine (T 3 ).…”

Section: Introductionmentioning

confidence: 99%

Regulation of TRH neurons and energy homeostasis-related signals under stress

Joseph‐Bravo

Jaimes-Hoy

Charlí

2015

Journal of Endocrinology

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Energy homeostasis relies on a concerted response of the nervous and endocrine systems to signals evoked by intake, storage, and expenditure of fuels. Glucocorticoids (GCs) and thyroid hormones are involved in meeting immediate energy demands, thus placing the hypothalamo-pituitary-thyroid (HPT) and hypothalamo-pituitary-adrenal axes at a central interface. This review describes the mode of regulation of hypophysiotropic TRHergic neurons and the evidence supporting the concept that they act as metabolic integrators. Emphasis has been be placed on i) the effects of GCs on the modulation of transcription of Trh in vivo and in vitro, ii) the physiological and molecular mechanisms by which acute or chronic situations of stress and energy demands affect the activity of TRHergic neurons and the HPT axis, and iii) the less explored role of non-hypophysiotropic hypothalamic TRH neurons. The partial evidence gathered so far is indicative of a contrasting involvement of distinct TRH cell types, manifested through variability in cellular phenotype and physiology, including rapid responses to energy demands for thermogenesis or physical activity and nutritional status that may be modified according to stress history.

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Section: Introductionmentioning

confidence: 99%

Regulation of TRH neurons and energy homeostasis-related signals under stress

Joseph‐Bravo

Jaimes-Hoy

Charlí

2015

Journal of Endocrinology

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“…They may transport to lysosomes or after TRH removal, dephosphorylate, and accumulate in recycling endosomes which reincorporate into the plasma membrane (resensitization). As b-arrestin is a scaffold for other signaling molecules, its interaction with the receptor permits cross talk with other pathways (Hinkle et al 2012). At the turn of the 21st century the development of bioluminescence resonance energy transfer, and other techniques to detect intermolecular interactions, demonstrated the formation of the TRHR homodimers induced by TRH (Hinkle et al 2012).…”

Section: Trh At the Anterior Pituitarymentioning

confidence: 99%

“…In GH pituitary tumor cells, TRH signalling via TRHR1 is conducted through the activation of a Gq/11 protein and phospholipase C b1 mechanism: the production of inositol 3 phosphate and diacyl gycerol affects cellular calcium homeostasis (mobilizing intracellular pools) and activation of protein kinase C (PKC) (Drummond 1986). The interaction of TRH with TRHR1 induces rapid desensitization of the response due to multiple events (Hinkle et al 2012). The ligand-receptor interaction induces receptor phosphorylation, within seconds, at multiple Ser/Thr sites in the cytoplasmic C-terminal tail by a GPCR kinase.…”

Section: Trh At the Anterior Pituitarymentioning

confidence: 99%

“…As b-arrestin is a scaffold for other signaling molecules, its interaction with the receptor permits cross talk with other pathways (Hinkle et al 2012). At the turn of the 21st century the development of bioluminescence resonance energy transfer, and other techniques to detect intermolecular interactions, demonstrated the formation of the TRHR homodimers induced by TRH (Hinkle et al 2012). TRH also provokes long-term transcriptional and posttranscriptional effects that diminish Trhr1 mRNA levels in rat pituitary GH3 cells, at least in part, by stimulating Trhr mRNA degradation (Narayanan et al 1992).…”

Section: Trh At the Anterior Pituitarymentioning

confidence: 99%

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60 YEARS OF NEUROENDOCRINOLOGY: TRH, the first hypophysiotropic releasing hormone isolated: control of the pituitary–thyroid axis

Joseph‐Bravo

Jaimes-Hoy

Uribe

et al. 2015

Journal of Endocrinology

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This review presents the findings that led to the discovery of TRH and the understanding of the central mechanisms that control hypothalamus-pituitary-thyroid axis (HPT) activity. The earliest studies on thyroid physiology are now dated a century ago when basal metabolic rate was associated with thyroid status. It took over 50 years to identify the key elements involved in the HPT axis. Thyroid hormones (TH: T 4 and T 3 ) were characterized first, followed by the semi-purification of TSH whose later characterization paralleled that of TRH. Studies on the effects of TH became possible with the availability of synthetic hormones. DNA recombinant techniques permitted the identification of all the elements involved in the HPT axis, including their mode of regulation. Hypophysiotropic TRH neurons, which control the pituitary-thyroid axis, were identified among other hypothalamic neurons which express TRH. Three different deiodinases were recognized in various tissues, as well as their involvement in cell-specific modulation of T 3 concentration. The role of tanycytes in setting TRH levels due to the activity of deiodinase type 2 and the TRH-degrading ectoenzyme was unraveled. TH-feedback effects occur at different levels, including TRH and TSH synthesis and release, deiodinase activity, pituitary TRH-receptor and TRH degradation. The activity of TRH neurons is regulated by nutritional status through neurons of the arcuate nucleus, which sense metabolic signals such as circulating leptin levels. Trh expression and the HPT axis are activated by energy demanding situations, such as cold and exercise, whereas it is inhibited by negative energy balance situations such as fasting, inflammation or chronic stress. New approaches are being used to understand the activity of TRHergic neurons within metabolic circuits. A historical perspective on the hypothalamic control of the thyroid axisThe advancement of any scientific field requires the combination of creative new ideas with the development of technologies and knowledge in related areas; understanding the function of the hypothalamus-pituitarythyroid axis (HPT) is no exception (Figs 1 and 2). Since the end of the 19th century, European physicians and surgeons associated neck swelling (thyroid enlargement, goiter), with iodine deficiency, cretinism, and myxoedema, This paper is part of a thematic review section on 60 years of neuroendocrinology. The Guest Editors for this section were Ashley Grossman and Clive Coen defining hypothyroid conditions. Magnus-Levy (1895) was the first to demonstrate that respiratory metabolism was increased in hyperthyroidism and decreased in myxoedema. Indirect calorimetry allowed measurements of basal metabolic rate (BMR) and the evaluation of thyroid activity in clinical practice (Du Bois & Du Bois 1915, Harris & Benedict 1918. Soon it was recognized that stressful conditions such as fever, acidosis, or starvation modify BMR (Rowe 1920). In 1919, levothyroxine (3,3 0 ,5,5 0 -tetraiodothyronine or T 4 ) was characterized, and then ...

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“…Thyrotrophs in the anterior pituitary express the TRH receptor, TRHR1. TRHR1 function is well characterised, notably rapidly desensitizing (Hinkle et al, 2012), a fact that should be taken into account in all assay development. Thyrotrophs produce thyrotropin or thyroid stimulating hormone (TSH).…”

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confidence: 99%

New Scoping Document on in vitro and ex vivo Assays for the Identification of Modulators of Thyroid Hormone Signalling

2014

OECD Series on Testing and Assessment

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Complete document available on OLIS in its original formatThis document and any map included herein are without prejudice to the status of or sovereignty over any territory, to the delimitation of international frontiers and boundaries and to the name of any territory, city or area. About the OECDThe Organisation for Economic Co-operation and Development (OECD) is an intergovernmental organisation in which representatives of 34 industrialised countries in North and South America, Europe and the Asia and Pacific region, as well as the European Commission, meet to co-ordinate and harmonise policies, discuss issues of mutual concern, and work together to respond to international problems. Most of the OECD's work is carried out by more than 200 specialised committees and working groups composed of member country delegates. Observers from several countries with special status at the OECD, and from interested international organisations, attend many of the OECD's workshops and other meetings. Committees and working groups are served by the OECD Secretariat, located in Paris, France, which is organised into directorates and divisions. This publication was developed in the IOMC context. The contents do not necessarily reflect the views or stated policies of individual IOMC Participating Organisations.The Inter-Organisation Programme for the Sound Management of Chemicals (IOMC) was established in 1995 following recommendations made by the 1992 UN Conference on Environment and Development to strengthen co-operation and increase international co-ordination in the field of chemical safety. The Participating Organisations are FAO, ILO, UNDP, UNEP, UNIDO, UNITAR, WHO, World Bank and OECD. The purpose of the IOMC is to promote co-ordination of the policies and activities pursued by the Participating Organisations, jointly or separately, to achieve the sound management of chemicals in relation to human health and the environment. FOREWORDThis new scoping document aims at bringing forward relevant in vitro and ex vivo thyroid assays to the attention of OECD member countries, to provide recommendations for their development/use, and also, to identify aspects/blocks of the thyroid signalling pathways that are not covered and would require further development of thyroid assays. ACRONYMS, ABBREVIATIONS AND DEFINITIONS ADMEAbsorption, distribution, metabolism and excretion AhR aryl hydrocarbon receptor AMA Amphibian Metamorphosis Assay (OECD TG 231) AOP adverse outcome pathway AOP is a sequence of events from the exposure of an individual or population to a chemical substance through a final adverse (toxic) effect at the individual level (for human health) or population level (for ecotoxicological endpoints). AR androgen receptorAssay An experimental system that can be used to obtain a range of information from chemical properties through the adverse effects of a substance. The terms 'assay' and 'test method' may be used interchangeably for wildlife as well as for mammalian studies (OECD, 2005) Indicators of Hormonal activit...

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Desensitization, Trafficking, and Resensitization of the Pituitary Thyrotropin-Releasing Hormone Receptor

Cited by 44 publications

References 120 publications

Regulation of TRH neurons and energy homeostasis-related signals under stress

Regulation of TRH neurons and energy homeostasis-related signals under stress

60 YEARS OF NEUROENDOCRINOLOGY: TRH, the first hypophysiotropic releasing hormone isolated: control of the pituitary–thyroid axis

New Scoping Document on in vitro and ex vivo Assays for the Identification of Modulators of Thyroid Hormone Signalling

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