Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2006) 11 P738

ECE2006 Poster Presentations Steroids (44 abstracts)

Long-term glucocorticoid repression of pro-opiomelanocortin (POMC) expression

A Eltobgi , L Abbott & J Newell-Price


Division of Clinical Sciences, Sheffield University, Northern General Hospital, Sheffield, United Kingdom.


Background: A functioning Hypothalamo-pituitary-adrenal (HPA) axis is essential for life. Prolonged high circulating levels of glucocorticoids inhibit pituitary Pro-opiomelanocortin (POMC) gene expression. Repression continues even in the absence of continued glucocorticoid exposure. To date there are no molecular explanations for this observation.

Hypothesis: Long-term exposure to glucocorticoids causes de-novo DNA methylation of the pituitary POMC promoter, or of the promoters of transcription factors that regulate POMC (Ptx1, NeuroD1, Tpit and Nur77), thereby imparting an inhibitory imprint and decreasing POMC expression even in the absence of ligand.

Methods: AtT-20 cells were cultured in standard growth media alone, or media supplemented with dexamethasone (10−7 M) for between 72 hours to 16 weeks. DNA and RNA were extracted by standard means. Real time quantitative PCR (qPCR) and standard RT-PCR was performed to establish expression of POMC, Ptx1, NeuroD1, Tpit and Nur77. Methylation patterns were assessed by bisulphite sequencing.

Results: At 4 weeks POMC and NeuroD1 expression were absent in treated cells and normal in untreated cells, whilst dexamethasone treatment did not affect expression of Tpit and Nur77 or Ptx1. The POMC promoter was, however, unmethylated in both treated and untreated cells.

Conclusions: De novo DNA methylation of the POMC promoter does not appear to be caused by long-term glucocorticoid exposure, at least for the doses and times studied. Prolonged glucocorticoid exposure inhibits expression of only one of the known transcription factors that stimulate POMC expression. Whether NeuroD1 is methylated in this context remains to be elucidated.

Volume 11

8th European Congress of Endocrinology incorporating the British Endocrine Societies

European Society of Endocrinology 
British Endocrine Societies 

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