Rapid intra-adrenal feedback regulation of glucocorticoid synthesis

J.J. Walker, F. Spiga, R. Gupta, Z. Zhao, S.L. Lightman, J.R. Terry

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)
73 Downloads (Pure)

Abstract

The hypothalamic–pituitary–adrenal axis is a vital neuroendocrine system that regulates the secretion of glucocorticoid hormones from the adrenal glands. This system is characterized by a dynamic ultradian hormonal oscillation, and in addition is highly responsive to stressful stimuli. We have recently shown that a primary mechanism generating this ultradian rhythm is a systems-level interaction where adrenocorticotrophin hormone (ACTH) released from the pituitary stimulates the secretion of adrenal glucocorticoids, which in turn feedback at the level of the pituitary to rapidly inhibit ACTH secretion. In this study, we combine experimental physiology and mathematical modelling to investigate intra-adrenal mechanisms regulating glucocorticoid synthesis. Our modelling results suggest that glucocorticoids can inhibit their own synthesis through a very rapid (within minutes), presumably non-genomic, intra-adrenal pathway. We present further evidence for the existence of a short time delay in this intra-adrenal inhibition, and also that at the initiation of each ACTH stimulus, this local feedback mechanism is rapidly antagonized, presumably via activation of the specific ACTH receptor (MC2R) signalling pathway. This mechanism of intra-adrenal inhibition enables the gland to rapidly release glucocorticoids while at the same time preventing uncontrolled release of glucocorticoids in response to large surges in ACTH associated with stress.
Original languageEnglish
Article number20140875
Number of pages10
JournalJournal of The Royal Society Interface
Volume12
Issue number102
DOIs
Publication statusPublished - 6 Jan 2015

Keywords

  • hypothalamic – pituitary – adrenal axis
  • mathematical modelling
  • adrenal gland
  • stress response
  • glucocorticoids

Fingerprint

Dive into the research topics of 'Rapid intra-adrenal feedback regulation of glucocorticoid synthesis'. Together they form a unique fingerprint.

Cite this