Dlk1 up-regulates Gli1 expression in male rat adrenal capsule cells through the activation of β1 integrin and ERK1/2

Endocrinology. 2013 Dec;154(12):4675-84. doi: 10.1210/en.2013-1211. Epub 2013 Sep 24.

Abstract

The development and maintenance of the zones of the adrenal cortex and their steroidal output are extremely important in the control of gluconeogenesis, the stress response, and blood volume. Sonic Hedgehog (Shh) is expressed in the adrenal cortex and signals to capsular cells, which can respond by migrating into the cortex and converting into a steroidogenic phenotype. Delta-like homologue 1 (Dlk1), a member of the Notch/Delta/Serrate family of epidermal growth factor-like repeat-containing proteins, has a well-established role in inhibiting adipocyte differentiation. We demonstrate that Shh and Dlk1 are coexpressed in the outer undifferentiated zone of the male rat adrenal and that Dlk1 signals to the adrenal capsule, activating glioma-associated oncogene homolog 1 transcription in a β1 integrin- and Erk1/2-dependent fashion. Moreover, Shh and Dlk1 expression inversely correlates with the size of the zona glomerulosa in rats after manipulation of the renin-angiotensin system, suggesting a role in the homeostatic maintenance of the gland.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Glands / cytology*
  • Animals
  • Cells, Cultured
  • Extracellular Signal-Regulated MAP Kinases / genetics
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Gene Expression Regulation / physiology*
  • Hedgehog Proteins / genetics
  • Hedgehog Proteins / metabolism
  • Integrin beta1 / genetics
  • Integrin beta1 / metabolism*
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism*
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Signal Transduction
  • Zinc Finger Protein GLI1

Substances

  • Dlk1 protein, rat
  • Gli1 protein, rat
  • Hedgehog Proteins
  • Integrin beta1
  • Intercellular Signaling Peptides and Proteins
  • Kruppel-Like Transcription Factors
  • Membrane Proteins
  • RNA, Messenger
  • Shh protein, rat
  • Zinc Finger Protein GLI1
  • Extracellular Signal-Regulated MAP Kinases