Dynamic responses of the adrenal steroidogenic regulatory network

Research output: Contribution to journalArticlepeer-review

Authors

  • Francesca Spiga
  • Jamie J. Walker
  • Zidong Zhao
  • Stafford L. Lightman

Colleges, School and Institutes

Abstract

The hypothalamic–pituitary–adrenal axis is a dynamic system regulating glucocorticoid hormone synthesis in the adrenal glands. Many key factors within the adrenal steroidogenic pathway have been identified and studied, but little is known about how these factors function collectively as a dynamic network of interacting components. To investigate this, we developed a mathematical model of the adrenal steroidogenic regulatory network that accounts for key regulatory processes occurring at different timescales. We used our model to predict the time evolution of steroidogenesis in response to physiological adrenocorticotropic hormone (ACTH) perturbations, ranging from basal pulses to larger stress-like stimulations (e.g., inflammatory stress). Testing these predictions experimentally in the rat, our results show that the steroidogenic regulatory network architecture is sufficient to respond to both small and large ACTH perturbations, but coupling this regulatory network with the immune pathway is necessary to explain the dissociated dynamics between ACTH and glucocorticoids observed under conditions of inflammatory stress.

Details

Original languageEnglish
Pages (from-to)E6466-E6474
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number31
Early online date17 Jul 2017
Publication statusPublished - 1 Aug 2017