Transcriptional regulation of episodic glucocorticoid secretion

Ying Liu, Lorna I Smith, Victoria Huang, Victoria Poon, Ana Coello, Mark Olah, Francesca Spiga, Stafford L Lightman, Greti Aguilera

Research output: Contribution to journalReview article (Academic Journal)peer-review

Abstract

Circadian and ultradian variations of basal glucocorticoid secretion and transient elevations during stress are essential for homeostasis. Using intronic qRT-PCR to measure changes in primary transcript (hnRNA) we have shown that secretory events induced by stress or ACTH injection are followed by episodic increases in transcription of rate limiting steroidogenic proteins, such as steroidogenic acute regulatory protein (StAR), cytochrome P450 side chain cleavage and melanocortin receptor associated protein. These transcriptional episodes imply rapid turnover of steroidogenic proteins and the need of de novo synthesis following each secretory event. In addition to episodic ACTH secretion, it is likely that intracellular feedback mechanisms at the adrenal fasciculata level contribute to the generation of episodes of transcription. The time relationship between activation and translocation of the CREB co-activator, transducer of regulated CREB activity (TORC) to the nucleus preceding transcriptional episodes suggest the involvement of TORC in the transcriptional activation of StAR and other steroidogenic proteins.

Original languageEnglish
Pages (from-to)62-70
Number of pages9
JournalMolecular and Cellular Endocrinology
Volume371
Issue number1-2
DOIs
Publication statusPublished - 22 May 2013

Bibliographical note

Published by Elsevier Ireland Ltd.

Keywords

  • Adrenal Glands/metabolism
  • Adrenocorticotropic Hormone/metabolism
  • Cyclic AMP Response Element-Binding Protein
  • Gene Expression Regulation
  • Glucocorticoids/metabolism
  • Humans
  • Phosphoproteins/biosynthesis
  • Receptors, Melanocortin/biosynthesis
  • Steroids/biosynthesis
  • Stress, Physiological
  • Transcription, Genetic
  • Transcriptional Activation

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