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Tanycytes modulate the feedback regulation of the axis by regulating the local thyroid hormone availability in the median eminence where the hypophysiotropic axons terminate. Recently, we showed that tanycytes produce diacylglycerol lipase alpha (DAGL\u03b1), the synthesizing enzyme of the endocannabinoid 2\u2010arachidonoylglycerol (2\u2010AG) that inhibits the release of TRH from the hypophysiotropic terminals in median eminence explants. To determine the importance of the endocannabinoid production of tanycytes, adult male Rax\u2010CreERT2\/\/DAGL\u03b1\n                    <jats:sup>fl\/fl<\/jats:sup>\n                    mice were treated with tamoxifen to induce a tanycyte specific decrease of DAGL\u03b1 expression (T\u2010DAGL\u03b1 KO). The effect of this genetic manipulation on the activity of the HPT axis was determined. Tanycyte specific decrease of DAGL\u03b1 expression resulted in an approximately 2\u2010fold increase of TSH\u03b2 mRNA level that was accompanied by increased levels of circulating free T4. The TRH mRNA level was, however, not influenced by the genetic manipulation. In addition to the effects on the HPT axis, the T\u2010DAGL\u03b1 KO mice showed increased fat mass ratio and decreased blood glucose levels. These data indicate that when endocannabinoid release of tanycytes is decreased, the disinhibition of the TRH release induces increased TSH synthesis and higher circulating T4\u00a0levels. Thus it suggests that in wild\u2010type mice, tanycytes exert a tonic inhibitory effect on the TRH release of hypophysiotropic axons. Furthermore, the endocannabinoid release of tanycytes also influences glucose homeostasis and fat deposition.\n                  <\/jats:p>","DOI":"10.1111\/jne.13079","type":"journal-article","created":{"date-parts":[[2021,12,17]],"date-time":"2021-12-17T11:51:49Z","timestamp":1639741909000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Tanycyte specific ablation of diacylglycerol lipase alpha stimulates the hypothalamic\u2010pituitary\u2010thyroid axis by decreasing the endocannabinoid mediated inhibition of TRH release"],"prefix":"10.1111","volume":"34","author":[{"given":"D\u00f3ra","family":"K\u0151v\u00e1ri","sequence":"first","affiliation":[{"name":"Laboratory of Integrative Neuroendocrinology Institute of Experimental Medicine Budapest Hungary"},{"name":"J\u00e1nos Szent\u00e1gothai Doctoral School of Neurosciences Neuroendocrinology Program Semmelweis University Budapest 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