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Title: Diurnal signalling of the vitamin A metabolite, retinoic acid, and its role in the mammalian pineal gland
Author: Ashton, Anna
ISNI:       0000 0004 7425 7765
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2018
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Vitamin A is an essential dietary component which primarily acts through its active metabolite, retinoic acid (RA), a potent transcriptional regulator that also has non-genomic activities. There is increasing evidence for a role for vitamin A in the regulation of circadian rhythms, and previous studies suggest that it serves important roles in the pineal gland, an integral component of the circadian system due to its function of melatonin production. However very little is currently known about how these effects are mediated, or about RA signalling in the pineal gland. This study aimed to establish whether RA is synthesised in the rat pineal gland and determine its role here. This included investigating whether RA is subject to diurnal changes in synthesis and signalling, and examining its involvement in the key rhythms in this gland: melatonin synthesis, kinase activation and clock gene expression. Organotypic culture of rat pineal glands, qPCR and western blotting were among the techniques employed to do this, as well as RA quantification using a reporter cell line. The rat pineal gland was found to produce RA and robust diurnal changes in synthesis were detected. Furthermore, diurnal changes in expression of RA signalling genes suggested there are corresponding changes in RA activity. RA was not found to rapidly regulate Aanat transcription, melatonin synthesis or clock gene expression in vitro, however it was found to rapidly down-regulate extracellular signal-regulated kinase (ERK) 1/2 phosphorylation. Furthermore, strong cytoplasmic expression of RA receptor α was detected in pinealocytes. These results suggest RA has a non-genomic role in the pineal gland and may be involved in driving the diurnal rhythm in kinase activation.
Supervisor: McCaffery, Peter Sponsor: Biotechnology and Biological Sciences Research Council (BBSRC) ; East of Scotland Bioscience Doctoral Training Partnership
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Tretinoin ; Circadian rhythms ; Melatonin ; Pineal gland