Predominately glucocorticoid agonist actions of ru-486 in young
specific-pathogen-free (spf) zucker rats.
Havel, Peter J., Bonnie L. Busch, Donald L. Curry, Patricia R.
Johnson, Mary F. Dallman, and Judith S. Stern.
Departments of Nutrition and Internal Medicine, Department of
Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine
and Section of Neurobiology, Physiology, and Behavior, Division of
Biological Sciences, University of California, Davis, CA 95616,
Department of Biology, Middle Tennessee Stae University,
Murfreesboro, TN 37132 and Department of Physiology, University of
California, San Francisco, CA 94143
APStracts 3:0113R, 1996.
Previous studies have demonstrated antiglucocorticoid actions for the
progesterone receptor antagonist, RU-486. In one study, daily
administration of this drug for 2 weeks, decreased food intake (FI)
and body weight gain (_BW) in obese, but not lean, conventionally
-housed 5 week-old female Zucker rats. We recently found that 2 week
administration of RU-486 attenuated _BW in lean, but not obese 12
week-old, male Zucker rats without affecting FI. In order to examine
the actions of RU-486 and its effects on FI and _BW, in young (5
week-old) specific-pathogen-free (SPF) male and female Zucker rats,
RU-486 was administered 30 mg/kg/day subcutaneously for 14 days. RU
-486 did not affect FI in obese or lean, male or female rats. RU-486
increased adrenal wt. (p< 0.05) overall and in lean female rats
and modestly decreased inguinal fat wt. 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 ACTH were elevated in vehicle
-treated obese female and male rats compared to lean rats, by 150-360%
(p< 0.0025) and by 32-38% (p< 0.05), respectively. 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 _BW. 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). 4) RU-486 administration suppresses the HPA axis
in obese rats.
Received 11 December 1995; accepted in final form 12 March 1996.
APS Manuscript Number R781-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 27 March 96