The posterior pituitary expresses the serotonin receptor 2C

Justin R. Welden, Zhaiyi Zhang, Marilyn J. Duncan, Marina Falaleeva, Timothy Wells, Stefan Stamm

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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.

Original languageEnglish
Pages (from-to)132-139
Number of pages8
JournalNeuroscience Letters
Volume684
DOIs
StatePublished - Sep 25 2018

Bibliographical note

Publisher Copyright:
© 2018

Keywords

  • Alternative splicing
  • Pituitary
  • Prader-Willi syndrome
  • Serotonin receptor 2C

ASJC Scopus subject areas

  • General Neuroscience

Fingerprint

Dive into the research topics of 'The posterior pituitary expresses the serotonin receptor 2C'. Together they form a unique fingerprint.

Cite this