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The posterior pituitary expresses the serotonin receptor 2C

Welden, Justin R., Zhang, Zhaiyi, Duncan, Marilyn J., Falaleeva, Marina, Wells, Timothy and Stamm, Stefan 2018. The posterior pituitary expresses the serotonin receptor 2C. Neuroscience Letters 684 , pp. 132-139. 10.1016/j.neulet.2018.06.051

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Abstract

The serotonin receptor 2C (5HT2C) is an important drug target to treat obesity and depression. Its pre-mRNA undergoes alternative splicing, encoding a short RNA1 isoform that is localized intracellularly and a full-length isoform (RNA2) that can reach the cell membrane. These splicing isoforms are deregulated in Prader-Willi syndrome (PWS), due to the loss of a trans-acting regulatory RNA, SNORD115. Here we show that the 5HT2C mRNA is expressed in the posterior pituitary, suggesting that 5HT2C mRNA is generated in the hypothalamus and subsequently conveyed by axonal transport. In the pituitary, the ratio of 5HT2C isoforms is regulated by feeding, and can be manipulated using a splice-site changing oligonucleotide injected into the blood. The pituitary expression of the 5HT2C mRNA may constitute a previously unknown mechanism whereby serotonin in the circulation or drugs targeting the 5HT2C might induce side-effects. Finally, the deregulation of 5HT2C splicing isoforms in PWS could contribute to the known hormonal imbalances.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Biosciences
Publisher: Elsevier
ISSN: 0304-3940
Date of First Compliant Deposit: 13 August 2018
Date of Acceptance: 27 June 2018
Last Modified: 14 Aug 2018 09:30
URI: http://orca.cf.ac.uk/id/eprint/114138

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