Effects of partial versus pure antiestrogens on ovulation and the pituitary-ovarian axis in the rat.
The present study was undertaken to compare the effects of the pure antiestrogen ZM 182780 (ZM) and the partial agonist tamoxifen (TAM) on ovulation and peripheral hormone levels in the rat. Adult female rats were treated with ZM (5 mg/kg/d) or TAM (5 mg/kg/d) and sacrificed at varying times during the estrous cycle. ZM and TAM were able to inhibit ovulation to nearly the same extent (60% and 70%, respectively). ZM induced a persistent diestrus whereas TAM led to a mixed picture in the vaginal smear. Both antiestrogens suppressed the preovulatory surge of LH, FSH and progesterone but had no effect on basal FSH values. In contrast to TAM, ZM caused an increase in basal levels of LH. Moreover, basal and preovulatory levels of estradiol and androgens were increased by ZM. By contrast, TAM decreased basal and preovulatory values of LH, estradiol, and androgens. These data suggest that ZM inhibits not only the positive but also negative feedback effect of estrogens and TAM seems to inhibit only the positive feedback. Moreover, it is conceivable that the suppressed preovulatory progesterone surge induced by ZM and TAM could be responsible for the antiovulatory effect.
Donath
J
J
Research Laboratories of Schering AG, Berlin, Experimental Oncology, Germany.
Nishino
Y
Y
D000818:Animals; D004958:Estradiol / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D004971:Estrus / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood / Q000378:metabolism; D000077267:Fulvestrant; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism; D010060:Ovulation / Q000187:drug effects / Q000502:physiology*; D010902:Pituitary Gland / Q000187:drug effects / Q000502:physiology*; D011388:Prolactin / Q000097:blood / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D013629:Tamoxifen / Q000494:pharmacology*
D004965:Estrogen Antagonists; D013629:Tamoxifen; D000077267:Fulvestrant; D004958:Estradiol; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone