Ultradian glucocorticoid exposure directs gene-dependent and tissue-specific mRNA expression patterns in vivo.
George CL., Birnie MT., Flynn BP., Kershaw YM., Lightman SL., Conway-Campbell BL.
In this paper we report differential decoding of the ultradian corticosterone signal by glucocorticoid target tissues. Pulsatile corticosterone replacement in adrenalectomised rats resulted in different dynamics of Sgk1 mRNA production, with a distinct pulsatile mRNA induction profile observed in the pituitary in contrast to a non-pulsatile induction in the prefrontal cortex (PFC). We further report the first evidence for pulsatile transcriptional repression of a glucocorticoid-target gene in vivo, with pulsatile regulation of Pomc transcription in pituitary. We have explored a potential mechanism for differences in the induction dynamics of the same transcript (Sgk1) between the PFC and pituitary. Glucocorticoid receptor (GR) activation profiles were strikingly different in pituitary and prefrontal cortex, with a significantly greater dynamic range and shorter duration of GR activity detected in the pituitary, consistent with the more pronounced gene pulsing effect observed. In the prefrontal cortex, expression of Gilz mRNA was also non-pulsatile and exhibited a significantly delayed timecourse of increase and decrease when compared to Sgk1, additionally highlighting gene-specific regulatory dynamics during ultradian glucocorticoid treatment.