Predominately glucocorticoid agonist actions of RU-486 in young specific-pathogen-free Zucker rats

Peter J Havel, Bonnie L. Busch, Donald L. Curry, Patricia R. Johnson, Mary F. Dallman, Judith S. Stern

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Previous studies have demonstrated antiglucocorticoid actions for the progesterone receptor antagonist RU-486. In one study, daily administration of this drug for 2 wk decreased food intake (FI) and body weight gain (ΔBW) in obese, but not lean, conventionally housed 5-wk-old female Zucker rats. We recently found that 2-wk administration of RU-486 attenuated ABW in lean but not obese 12-wk-old male Zucker rats without affecting FI. To examine the actions of RU-486 and its effects on FI and ΔBW in young (5-wk-old) specific-pathogen-free (SPF) male and female Zucker rats, RU-486 was administered at 30 mg · kg-1 · day-1 subcutaneously for 14 days. RU- 486 did not affect FI in obese or lean male or female rats. RU-486 increased adrenal weight (P < 0.05) overall and in lean female rats and modestly decreased inguinal fat weight overall and in obese female rats (P < 0.01), suggesting some antiglucocorticoid activity in these animals. However, RU- 486 also decreased thymus weight by 18-31% (P < 0.0001), increased plasma glucose by 10-16 mg/dl (P < 0.002), and increased plasma insulin by 47% in obese male rats (P < 0.028), demonstrating glucocorticoid agonist actions for the drug. Plasma corticosterone (B) and adrenocorticotropic hormone (ACTH) were elevated in vehicle-treated obese female and male rats by 150-360% (P < 0.0025) and 32-38% (P < 0.05), respectively, compared with lean rats. RU-486 treatment lowered the elevated plasma B and ACTH levels in obese female and male rats (both P < 0.02 vs. vehicle), a glucocorticoid agonist effect. We conclude that in young SPF Zucker rats 1) RU-486 administration does not alter FI or ΔBW, 2) RU-486 has predominately glucocorticoid agonist actions in several tissues, 3) obese animals have increased hypothalamic-pituitary- adrenal (HPA) axis activity (plasma B and ACTH), and 4) RU-486 administration suppresses the HPA axis in obese rats.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume271
Issue number3 40-3
StatePublished - Sep 1996

Keywords

  • adrenal
  • adrenocorticotropic hormone
  • corticosterone
  • glucagon
  • glucose
  • insulin
  • mifepristone
  • pancreatic polypeptide
  • thymus

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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