Effects of continuous infusions of 4-hydroxyoestradiol and oestradiol on plasma LH-levels in the ovariectomized ewe.

Ovariectomized ewes were infused over a period of 12 h at constant rates with different doses of the catecholoestrogen 4-hydroxyoestradiol (4-OHE2) or the primary oestrogen oestradiol (E2) via a catheter placed in the right atrium. Blood samples were drawn every hour for a total period of 48 h starting 1 h before the beginning of the steroid infusion. Luteinizing hormone (LH), 4-OHE2 and E2 concentrations were measured in these samples by specific radioimmunoassays. Infusions of low doses E2 (0.5 microgram/h) or 4-OHE2 (2 micrograms/h) caused only a suppression of LH-secretion. At doses of 1 microgram E2/h or 5 micrograms 4-OHE2/h this negative effect was followed by inconsistent elevations of plasma LH. Beyond this threshold dose, E2 at infusion rates of 2, 5 and 10 micrograms/h and 4-OHE2 at infusion rates of 10, 25 and 50 micrograms/h produced the negative effect and massive LH-surges. At still higher infusion rates (E2: 20 micrograms/h, 4-OHE2: 100 micrograms/h) lower elevations of plasma LH levels were observed. 4-OHE2 had to be infused at 4-5 times higher rates than E2 to obtain comparable plasma concentrations of either oestrogen. Under this condition the effects of 4-OHE2 and E2 were similar indicating that 4-OHE2 has the same potency as E2 at central target sites.