title: Ultradian glucocorticoid exposure directs gene-dependent and tissue-specific mRNA expression patterns in vivo.
abstract: 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.
authors: Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, School of Clinical Sciences, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol, BS1 3NY, UK; CGAT, MRC Weatherall Institute of Molecular Medicine Centre for Computational Biology, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS, UK. Electronic address: Charlotte.George@imm.ox.ac.uk.
authors: Charlotte L
authors: CL
authors: George
authors: Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, School of Clinical Sciences, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol, BS1 3NY, UK. Electronic address: Matthew.Birnie@bristol.ac.uk.
authors: Matthew T
authors: MT
authors: Birnie
authors: Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, School of Clinical Sciences, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol, BS1 3NY, UK. Electronic address: Ben.Flynn@bristol.ac.uk.
authors: Benjamin P
authors: BP
authors: Flynn
authors: Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, School of Clinical Sciences, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol, BS1 3NY, UK. Electronic address: Y.Kershaw@bristol.ac.uk.
authors: Yvonne M
authors: YM
authors: Kershaw
authors: Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, School of Clinical Sciences, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol, BS1 3NY, UK. Electronic address: Stafford.Lightman@bristol.ac.uk.
authors: Stafford L
authors: SL
authors: Lightman
authors: Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, School of Clinical Sciences, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol, BS1 3NY, UK. Electronic address: B.Conway-Campbell@bristol.ac.uk.
authors: Becky L
authors: BL
authors: Conway-Campbell
mesh_terms: D000818:Animals; D003345:Corticosterone / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology*; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D009928:Organ Specificity / Q000187:drug effects / Q000235:genetics*; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D000071218:Ultradian Rhythm / Q000187:drug effects / Q000235:genetics*; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D003345:Corticosterone; D005938:Glucocorticoids; D017874:Immediate-Early Proteins; D011333:Pro-Opiomelanocortin; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D000099184:Serum-Glucocorticoid Regulated Kinases
keywords: GR; Glucocorticoids; Pituitary; Prefrontal cortex; Transcription; Ultradian rhythm