| Title: |
Predominately glucocorticoid agonist actions of RU-486 in young specific-pathogen-free Zucker rats |
| Authors: |
Havel, PJ; Busch, BL; Curry, DL; Johnson, PR; Dallman, MF; Stern, JS |
| Source: |
American Journal of Physiology, vol 271, iss 3 |
| Publisher Information: |
eScholarship, University of California |
| Publication Year: |
1996 |
| Collection: |
University of California: eScholarship |
| Subject Terms: |
5202 Biological Psychology (for-2020); 3214 Pharmacology and Pharmaceutical Sciences (for-2020); 32 Biomedical and Clinical Sciences (for-2020); 52 Psychology (for-2020); Nutrition (rcdc); Obesity (rcdc); Metabolic and endocrine (hrcs-hc); Adipose Tissue (mesh); Adipose Tissue; Brown (mesh); Animals (mesh); Animals; Newborn (mesh); Blood Glucose (mesh); Body Weight (mesh); Eating (mesh); Female (mesh); Germ-Free Life (mesh); Glucocorticoids (mesh); Hormone Antagonists (mesh); Hormones (mesh); Male (mesh); Mifepristone (mesh); Obesity (mesh); Organ Size (mesh); Rats (mesh); Rats; Zucker (mesh); Reference Values (mesh); mifepristone |
| Subject Geographic: |
r710 - r717 |
| Description: |
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 (delta BW) in obese, but not lean, conventionally housed 5-wk-old female Zucker rats. We recently found that 2-wk administration of RU-486 attenuated delta BW 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 delta BW 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 delta 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), and 4) RU-486 administration suppresses the HPA axis in obese rats. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
unknown |
| Relation: |
qt8b19p8jv; https://escholarship.org/uc/item/8b19p8jv; https://escholarship.org/content/qt8b19p8jv/qt8b19p8jv.pdf |
| DOI: |
10.1152/ajpregu.1996.271.3.r710 |
| Availability: |
https://escholarship.org/uc/item/8b19p8jv; https://escholarship.org/content/qt8b19p8jv/qt8b19p8jv.pdf; https://doi.org/10.1152/ajpregu.1996.271.3.r710 |
| Rights: |
public |
| Accession Number: |
edsbas.6CD33E88 |
| Database: |
BASE |