TY - JOUR
T1 - Predominately glucocorticoid agonist actions of RU-486 in young specific-pathogen-free Zucker rats
AU - Havel, Peter J
AU - Busch, Bonnie L.
AU - Curry, Donald L.
AU - Johnson, Patricia R.
AU - Dallman, Mary F.
AU - Stern, Judith S.
PY - 1996/9
Y1 - 1996/9
N2 - 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.
AB - 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.
KW - adrenal
KW - adrenocorticotropic hormone
KW - corticosterone
KW - glucagon
KW - glucose
KW - insulin
KW - mifepristone
KW - pancreatic polypeptide
KW - thymus
UR - http://www.scopus.com/inward/record.url?scp=0029796709&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029796709&partnerID=8YFLogxK
M3 - Article
C2 - 8853395
AN - SCOPUS:0029796709
VL - 271
JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
SN - 1931-857X
IS - 3 40-3
ER -