Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2003) 5 P121

BES2003 Poster Presentations Endocrine Tumours and Neoplasia (47 abstracts)

Differential modulation of key steroidogenic enzymes through orphan nuclear transcriptional regulation may control the diverse production of cortisol and adrenal androgens

SN Kelly 1,3 , JI Mason 2 , TJ Mc Kenna 1,3 & LS Young 3,4


1Department of Endocrinology, St Vincents University Hospital, Dublin, Ireland; 2Department of Reproductive and Developmental Sciences, University of Edinburgh Medical School, Scotland, UK; 3Department of Surgery, St Vincents University Hospital, Dublin, Ireland; 4Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Ireland.


The capacity of the adrenal to produce cortisol is controlled in part by the transcription of 21 hydroxylase(CYP21) and production of androgens by 17 hydroxylase/17-20 lyase(CYP17) in response to secretogoues including ACTH, angiotensin-II(A-II) and forskolin. Both mRNA and protein expression of CYP21 was upregulated in the presence of forskolin and A-II alone and in combination in vitro H-295 adrenocortical cells, as detected by northern and western blotting. Whereas, mRNA expression of CYP17 was up-regulated in the presence of forskolin and insulin. CYP17 protein expression was found to be increased in the presence of insulin and A-II. Response elements for the orphan nuclear receptor SF-1 and nur-77 were identified on the promoter region of CYP17 and CYP21. The ability of SF-1 and nur-77 to regulate transcription of these enzymes was examined. SF-1 was expressed throughout the adrenal cortex and was localised predominantly to the nucleus. Forskolin, A-II and insulin increased the protein expression and nuclear translocation of SF-1. Using mobility shift assays increased binding of SF-1 to its response element in the presence of forskolin, A-II and insulin but not A-II in combination with forskolin was observed. Nur-77 was expressed primarily in the zona fasciculata. Increased protein expression of nur-77 and the greatest binding of nur-77 to its response element was seen when cells were stimulated with A-II in combination with forskolin. Insulin had no effect on protein expression or activity of nur-77. These data indicate that nur-77 may regulate steroid enzyme genes relevant to cortisol production and thereby regulate differential cortisol and adrenal androgen production.

Volume 5

22nd Joint Meeting of the British Endocrine Societies

British Endocrine Societies 

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