Modulation of LH-secretion in ovariectomized ewes by constant infusions of oestradiol and 4-hydroxyoestradiol: effects of varying infusion times and of high oestrogen doses

Abstract

Abstract. Ovariectomized ewes were infused for different times (2–24 h) during the breeding season (September to Februray) with oestradiol (E2, 2 μg/h) or the catecholoestrogen 4-hydroxyoestradiol (4-OHE2, 10 μg/h). At these infusion rates comparable plasma levels of E2 and 4-OHE2 were obtained when steady state was reached after 3 h (E2: 20 ± 4 pg/ml; 4-OHE2: 22 ± 3 pg/ml). When E2 was infused for at least 6 h, all animals had significant LH-surges, starting 14-16 h after the beginning of oestrogen treatment, even when E2 was infused for up to 24 h. 4-OHE2, however, had only to be infused for 4 h to induce significant LH-surges in all animals tested. When E2 was infused for 12 h at a rate of 100 μg/h, the LH-surges in these ewes were significantly lower than the LH-surges in the same animals treated for 12 h with E2at a rate of 2 μg/h. These data indicate: Once E2 has been administered at a specific infusion rate for a critical time period of 6 h, LH-surges occur, no matter whether the E2-infusion is continued or stopped. For the catecholoestrogen 4-OHE2 this critical time period amounts only to 4 h, if comparable plasma levels of either oestrogen are achieved. This might hint at a prolonged intracellular action of 4-OHE2 as compared to E2. At extremely high infusion rates of E2 (100 μg/h for 12 h) the positive oestrogen effect is significantly impaired, a finding supporting the concept of a bell-shaped dose-response relationship between oestrogens and their positive effect on LH-secretion.