Effects of enclomiphene on estradiol-induced changes in LH secretion in ewes.
Experiments were conducted to characterize the ability of the antiestrogen enclomiphene (ENC) to block the effects of estradiol on secretion of LH in ovariectomized ewes. To determine whether ENC could block an estradiol-induced LH surge, ewes (n = 4/group) were administered 10 to 250 mg ENC followed 30 min later by 25 micrograms estradiol. Ten or 25 mg ENC suppressed the estradiol-induced LH surge in one of four ewes, whereas 100- or 250-mg doses suppressed the LH surge in three and four of four ewes, respectively. In ewes that received a single treatment of 100 mg ENC plus 25 micrograms estradiol, serum concentrations of LH remained below 1 ng/ml for 3 wk. Compared with untreated ewes, the number of pituitary GnRH receptors was elevated (P less than .05) at 12 d and 28 d, but pituitary content of LH had decreased (P less than .05) by 28 d in ewes treated with 100 mg ENC. To determine whether ENC could block the inhibitory effects of estradiol on serum concentrations of LH, ewes received injections of .03, .1, 1 or 10 mg ENC every 4 d. Half the ewes treated with each dose also received estradiol implants. Injection of .03, .1 or 1 mg ENC alone did not affect serum concentrations of LH, whereas the 10-mg dose decreased serum concentrations of LH below 1 ng/ml by wk 1 of treatment. No dose prevented the inhibition of serum concentrations of LH caused by estradiol implants. In ovariectomized ewes, ENC was antagonistic to estradiol; it prevented the positive effects of estradiol required to induce an LH surge.(ABSTRACT TRUNCATED AT 250 WORDS)
Gregg
D W
DW
Dept. of Physiol., Colorado State University, Fort Collins 80523.
Nett
T M
TM
D000818:Animals; D001667:Binding, Competitive; D002996:Clomiphene / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D064695:Enclomiphene; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D007536:Isomerism; D007986:Luteinizing Hormone / Q000378:metabolism*; D010902:Pituitary Gland / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D012756:Sheep / Q000378:metabolism*
D011960:Receptors, Estrogen; D002996:Clomiphene; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D007986:Luteinizing Hormone; D064695:Enclomiphene