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.

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Ovariectomized ewes were infused for different times (2-24 h) during the breeding season (September to February) with oestradiol (E2, 2 micrograms/h) or the catecholoestrogen 4-hydroxyoestradiol (4-OHE2, 10 micrograms/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 micrograms/h, the LH-surges in these ewes were significantly lower than the LH-surges in the same animals treated for 12 h with E2 at a rate of 2 micrograms/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 micrograms/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.