Nishino Tsuyuki, Yamanouchi Hiroshi, Ishibashi Kanako, Hirtreiter Christian, Nishino Yukishige
Experimental Toxicology and Ecology, Reproduction Toxicology, BASF SE, Carl-Bosch-Strasse 38, Ludwigshafen, Germany.
J Steroid Biochem Mol Biol. 2009 Apr;114(3-5):152-60. doi: 10.1016/j.jsbmb.2009.01.021. Epub 2009 Feb 6.
The effects of ZK 191703 (ZK), a pure antiestrogen, on ovulation, follicle development and peripheral hormone levels were investigated in rats with 4-day estrus cycle and gonadotropin-primed immature rats in comparison to tamoxifen (TAM)-treatment. In adult rats, a single s.c. injection of ZK (5 mg/kg) or TAM (5 mg/kg) at an early stage of the estrus cycle (diestrus 9:00) inhibited ovulation, and was associated with suppression of the surge of preovulatory LH, FSH and progesterone. In rats treated with ZK or TAM at a late stage of the estrus cycle (proestrus 9:00), no inhibitory effects on ovulation, the gonadotropin and progesterone surge were detected. ZK treatment at diestrus 9:00, in contrast to TAM, increased the baseline LH level. When immature rats were treated with antiestrogens in the earlier stage of follicular development, 6 and 30 h but not 48 h or later after injection of gonadotropin (PMSG), ovulation was attenuated, associated with a lowered progesterone level. Unruptured preovulatory follicles were found in most of the ovaries from anovulatory animals treated with ZK or TAM. Antiestrogens, ZK and TAM administered at an early phase of the estrus cycle delay the follicular development functionally and inhibit ovulation in rats and suppression of the preovulatory progesterone surge.
