The impact of early-life stress on corticosteroid carrier protein levels and 11β-hydroxysteroid dehydrogenase 1 expression in adolescent rats

Pharmacol Rep. 2019 Apr;71(2):347-350. doi: 10.1016/j.pharep.2018.11.003. Epub 2018 Nov 28.

Abstract

Background: Corticosteroid-binding globulin (CBG), albumin and 11β-hydroxysteroid dehydrogenase (11β-HSD) enzymes play crucial roles in the bioavailability of glucocorticoids. Downstream of the adrenal glands, these proteins affect glucocorticoid levels in target tissues. Early-life stress (ELS) is known to program glucocorticoid action at many levels. The effects of ELS on the concentrations and synthesis of CBG and albumin and on the expression of 11β-HSD remain unclear.

Methods: The maternal separation (MS) procedure in rats on postnatal days 1-14 was used as a model of ELS. On postnatal day 35 (adolescence), the serum corticosterone, CBG and albumin concentrations of male rats were measured by ELISA, while the mRNA and protein levels of CBG, albumin and 11β-HSD1 in the liver and brain were examined by RT-qPCR and Western blot, respectively.

Results: Under basal conditions, MS rats displayed lower levels of serum CBG and albumin. However, MS did not affect CBG or albumin synthesis in the liver, suggesting that the half-life and/or secretion of these proteins were influenced by MS. Additionally, MS rats showed increased protein expression of 11β-HSD1, specifically in the medial prefrontal cortex.

Conclusions: These results indicate that ELS may potentially program glucocorticoid action through its effects on glucocorticoid bioavailability in tissues.

Keywords: 11β-hydroxysteroid dehydrogenase; Albumin; Corticosteroid-binding globulin; Corticosterone; Early-life stress; Liver.

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / isolation & purification*
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / metabolism*
  • Animals
  • Brain / metabolism
  • Corticosterone / blood
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Glucocorticoids / metabolism
  • Liver / metabolism
  • Male
  • Maternal Deprivation*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Stress, Psychological / physiopathology*
  • Transcortin / metabolism

Substances

  • Glucocorticoids
  • RNA, Messenger
  • Transcortin
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1
  • Corticosterone