The capacity of the adrenal to produce steroids is controlled in part through the transcriptional regulation of steroid enzymes. Steroidogenic factor 1 (SF-1), an orphan nuclear receptor is thought to be central to the transcriptional regulation of all steroid hydroxylase enzymes. Recently co-regulatory proteins have been implicated in the modulation of nuclear receptor transcriptional activity. We hypothesised that classic and novel secretogogues, including forskolin, angiotensin II (A-II) and insulin can regulate expression and activity of SF-1 and the co-regulator protein, steroid receptor co-activator (SRC-1). Using northern and western blotting increases in SF-1 mRNA and protein were detected in H-295 adrenocortical cells, treated with forskolin, A-II and insulin. Increased binding of SF-1 to its response element was also detected in the presence of these secretogogues. SF-1 and SRC-1 were co-localised to the same adrenocortical cells throughout the adrenal cortex, and furthermore SF-1 transcripts were shown to be regulated in the presence of these secretogogues. These data implicate SRC-1 in the secretogogue induced transcriptional regulation of steroid enzymes by SF-1.
22 - 24 Mar 2004
British Endocrine Societies