Retinoic Acid Signalling in the Pineal Gland Is Conserved across Mammalian Species and Its Transcriptional Activity Is Inhibited by Melatonin

Anna Ashton* (Corresponding Author), Jason Clark, Julia Fedo, Angelo Sementilli, Yara D Fragoso, Peter McCaffery

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)
5 Downloads (Pure)


The pineal gland is integral to the circadian timing system due to its role in nightly melatonin production. Retinoic acid (RA) is a potent regulator of gene transcription and has previously been found to exhibit diurnal changes in synthesis and signalling in the rat pineal gland. This study investigated the potential for the interaction of these two systems. PCR was used to study gene expression in mouse and human pineal glands, ex-vivo organotypic cultured rat pineal gland and cell lines. The mouse and human pineal glands were both found to express the necessary components required for RA signalling. RA influences the circadian clock in the brain, therefore the short-term effect of RA on clock gene expression was determined in ex vivo rat pineal glands but was not found to rapidly regulate Per1, Per2, Bmal1, or Cry1. The interaction between RA and melatonin was also investigated and, unexpectedly, melatonin was found to suppress the induction of gene transcription by RA. This study demonstrates that pineal expression of the RA signalling system is conserved across mammalian species. There is no short-term regulation of the circadian clock but an inhibitory effect of melatonin on RA transcriptional activity was demonstrated, suggesting that there may be functional cross-talk between these systems.

Original languageEnglish
Article number286
Number of pages15
Issue number2
Publication statusPublished - 11 Jan 2023

Bibliographical note

This article belongs to the Collection Functions of Nuclear Receptors

We thank David Hazlerigg for providing the MSM mice. qPCR was performed with the help of the Institute of Medical Sciences qPCR Core Facility at the University of Aberdeen.

Data Availability Statement

All data are contained within the article or supplementary material. Raw data are available on request


  • Rats
  • Mice
  • Humans
  • Animals
  • Pineal Gland/metabolism
  • Melatonin/pharmacology
  • Tretinoin/pharmacology
  • Signal Transduction
  • Mammals/metabolism


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