Dataset Information

A Glial-Neuronal Circuit in the Median Eminence Regulates Thyrotropin-Releasing Hormone-Release via the Endocannabinoid System.

ABSTRACT: Based on the type-I cannabinoid receptor (CB1) content of hypophysiotropic axons and the involvement of tanycytes in the regulation of the hypothalamic-pituitary-thyroid (HPT) axis, we hypothesized that endocannabinoids are involved in the tanycyte-induced regulation of TRH release in the median eminence (ME). We demonstrated that CB1-immunoreactive TRH axons were associated to DAGL?-immunoreactive tanycyte processes in the external zone of ME and showed that endocannabinoids tonically inhibit the TRH release in this tissue. We showed that glutamate depolarizes the tanycytes, increases their intracellular Ca2+ level and the 2-AG level of the ME via AMPA and kainite receptors and glutamate transport. Using optogenetics, we demonstrated that glutamate released from TRH neurons influences the tanycytes in the ME. In summary, tanycytes regulate TRH secretion in the ME via endocannabinoid release, whereas TRH axons regulate tanycytes by glutamate, suggesting the existence of a reciprocal microcircuit between tanycytes and TRH terminals that controls TRH release.

SUBMITTER: Farkas E

PROVIDER: S-EPMC7058404 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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A Glial-Neuronal Circuit in the Median Eminence Regulates Thyrotropin-Releasing Hormone-Release via the Endocannabinoid System.

Farkas Erzsébet E Varga Edina E Kovács Balázs B Szilvásy-Szabó Anett A Cote-Vélez Antonieta A Péterfi Zoltán Z Matziari Magdalini M Tóth Mónika M Zelena Dóra D Mezriczky Zsolt Z Kádár Andrea A Kővári Dóra D Watanabe Masahiko M Kano Masanobu M Mackie Ken K Rózsa Balázs B Ruska Yvette Y Tóth Blanka B Máté Zoltán Z Erdélyi Ferenc F Szabó Gábor G Gereben Balázs B Lechan Ronald M RM Charli Jean-Louis JL Joseph-Bravo Patricia P Fekete Csaba C

iScience 20200217 3

Based on the type-I cannabinoid receptor (CB1) content of hypophysiotropic axons and the involvement of tanycytes in the regulation of the hypothalamic-pituitary-thyroid (HPT) axis, we hypothesized that endocannabinoids are involved in the tanycyte-induced regulation of TRH release in the median eminence (ME). We demonstrated that CB1-immunoreactive TRH axons were associated to DAGLα-immunoreactive tanycyte processes in the external zone of ME and showed that endocannabinoids tonically inhibit t ...[more]

PMID: 32143135

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Project description:Thyrotropin releasing hormone (TRH: Glp-His-Pro-NH2) is a peptide mainly produced by brain neurons. In mammals, hypophysiotropic TRH neurons of the paraventricular nucleus of the hypothalamus integrate metabolic information and drive the secretion of thyrotropin from the anterior pituitary, and thus the activity of the thyroid axis. Other hypothalamic or extrahypothalamic TRH neurons have less understood functions although pharmacological studies have shown that TRH has multiple central effects, such as promoting arousal, anorexia and anxiolysis, as well as controlling gastric, cardiac and respiratory autonomic functions. Two G-protein-coupled TRH receptors (TRH-R1 and TRH-R2) transduce TRH effects in some mammals although humans lack TRH-R2. TRH effects are of short duration, in part because the peptide is hydrolyzed in blood and extracellular space by a M1 family metallopeptidase, the TRH-degrading ectoenzyme (TRH-DE), also called pyroglutamyl peptidase II. TRH-DE is enriched in various brain regions but is also expressed in peripheral tissues including the anterior pituitary and the liver, which secretes a soluble form into blood. Among the M1 metallopeptidases, TRH-DE is the only member with a very narrow specificity; its best characterized biological substrate is TRH, making it a target for the specific manipulation of TRH activity. Two other substrates of TRH-DE, Glp-Phe-Pro-NH2 and Glp-Tyr-Pro-NH2, are also present in many tissues. Analogs of TRH resistant to hydrolysis by TRH-DE have prolonged central efficiency. Structure-activity studies allowed the identification of residues critical for activity and specificity. Research with specific inhibitors has confirmed that TRH-DE controls TRH actions. TRH-DE expression by β2-tanycytes of the median eminence of the hypothalamus allows the control of TRH flux into the hypothalamus-pituitary portal vessels and may regulate serum thyrotropin secretion. In this review we describe the critical evidences that suggest that modification of TRH-DE activity in tanycytes, and/or in other brain regions, may generate beneficial consequences in some central and metabolic disorders and identify potential drawbacks and missing information needed to test these hypotheses.

Project description:It is known that growth hormone (GH) is expressed in immune cells, where it exerts immunomodulatory effects. However, the mechanisms of expression and release of GH in the immune system remain unclear. We analyzed the effect of growth hormone-releasing hormone (GHRH), thyrotropin-releasing hormone (TRH), ghrelin (GHRL), and somatostatin (SST) upon GH mRNA expression, intracellular and released GH, Ser133-phosphorylation of CREB (pCREBS133), intracellular Ca2+ levels, as well as B-cell activating factor (BAFF) mRNA expression in bursal B-lymphocytes (BBLs) cell cultures since several GH secretagogues, as well as their corresponding receptors (-R), are expressed in B-lymphocytes of several species. The expression of TRH/TRH-R, ghrelin/GHS-R1a, and SST/SST-Rs (Subtypes 1 to 5) was observed in BBLs by RT-PCR and immunocytochemistry (ICC), whereas GHRH/GHRH-R were absent in these cells. We found that TRH treatment significantly increased local GH mRNA expression and CREB phosphorylation. Conversely, SST decreased GH mRNA expression. Additionally, when added together, SST prevented TRH-induced GH mRNA expression, but no changes were observed in pCREBS133 levels. Furthermore, TRH stimulated GH release to the culture media, while SST increased the intracellular content of this hormone. Interestingly, SST inhibited TRH-induced GH release in a dose-dependent manner. The coaddition of TRH and SST decreased the intracellular content of GH. After 10 min. of incubation with either TRH or SST, the intracellular calcium levels significantly decreased, but they were increased at 60 min. However, the combined treatment with both peptides maintained the Ca2+ levels reduced up to 60-min. of incubation. On the other hand, BAFF cytokine mRNA expression was significantly increased by TRH administration. Altogether, our results suggest that TRH and SST are implicated in the regulation of GH expression and release in BBL cultures, which also involve changes in pCREBS133 and intracellular Ca2+ concentration. It is likely that TRH, SST, and GH exert autocrine/paracrine immunomodulatory actions and participate in the maturation of chicken BBLs.

Dataset Information

A Glial-Neuronal Circuit in the Median Eminence Regulates Thyrotropin-Releasing Hormone-Release via the Endocannabinoid System.

Publications

A Glial-Neuronal Circuit in the Median Eminence Regulates Thyrotropin-Releasing Hormone-Release via the Endocannabinoid System.

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