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Title: Candidate role for nuclear hormone receptors in gene regulation in magnocellular neurones in the hypothalamus
Author: Armstrong, M. E.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2001
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In this thesis, the expression of the unliganded, orphan receptor NGFI-B was investigated in rats which were exposed to acute- and chronic hyperosmotic stress, acute suckling and central administration of histamine. These stimuli are proven activators of OT and VP transcription in magnocellular supraoptic neurones. Using in situ hybridisation, a significant induction of NGFI-B mRNA was demonstrated in magnocellular neurones in response to acute-hyperosmotic stress and central administration of histamine, but not chronic-hyperosmotic stress or acute suckling. This may imply a differential role for NGFI-B in gene regulation in magnocellular neurones. The expression of other NHRs in the SON of acutely hyperosmotic animals was investigated using a PCR-based homology cloning strategy. This cloning strategy was based on the high degree of homology which exists within the DNA-binding domain (DBD) of all NHR superfamily members. Using degenerate primers directed against the highly conserved DBD, a number of NHRs were PCR amplified from a microdissected SON of acutely hyperosmotic rats including COUP-TFI, COUP-TFII, ERα, NGFI-B, TR4, THRα, ERR1, GCNF, COUP-gamma, Nor1 and a FTZ-F1 isoform(s). An investigation was made of the expression of the most relevant NHRs found during cloning in magnocellular neurones using in situ hybridisation. Results from these studies revealed the presence of mRNA for the orphans Nor1 and COUP-gamma in the SON of acutely hyperosmotic rats. NGFI-B and Nor1 are known to act as transcriptional activators, while COUP-gamma acts as a transcriptional repressor. Regulation of the OT and VP genes by these orphans may be mediated through the AGGTCA half-sites and DRO motif present in their promoter regions.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available