The objective of this study was to determine whether anti-oestrogens (nafoxidine, MER-25) would block the suppressive effects of
ACTH on gonadotrophin secretion in immature rats. Female rats were castrated at 25-26 days of age, and an Alzet osmotic minipump containing
ACTH (1-24) or saline was implanted in each animal.
ACTH was administered at a rate of 1 IU/day by constant infusion. Beginning on the day of surgery, animals were injected daily for 5 days with 0.25, 5 or 25 micrograms/100 g
body weight of
nafoxidine or 5 mg
MER-25 and sacrificed on the sixth day following
castration.
ACTH lowered serum LH concentrations and increased pituitary LH levels. Serum
androstenedione concentrations were more than two times greater in
ACTH-infused than in control rats, but serum oestrone levels were not affected. Serum
testosterone and
oestradiol concentrations in
ACTH-infused rats remained below levels of detection. Administration of 0.25 micrograms of
nafoxidine prevented the suppressive effects of
ACTH on serum LH. Serum levels of LH in these animals were comparable to saline-treated controls (418 +/- 94 vs 443 +/- 73 ng/ml). The two higher doses of
nafoxidine and
MER-25 were ineffective in suppressing the actions of
ACTH on serum LH.
MER-25 reduced serum LH values in both controls and
ACTH-infused rats. Serum FSH concentrations were not altered by
ACTH or
nafoxidine treatment.
MER-25 elevated pituitary FSH concentrations in both control and
ACTH-infused rats.(ABSTRACT TRUNCATED AT 250 WORDS)