Dose-dependent effects of chronic treatment with estradiol or progesterone on LH secretion in ovariectomized rats

Ovariectomized (OVX) Sprague-Dawley rats bearing atrial cannulae were implanted subcutaneously with fused pellets containing estradiol (E2) or progesterone (P4). Variable doses of E2 (0.1, 0.5, 1 and 5%) or P4 (10, 50, 75, 100%) were achieved by varying the ratio of the hormone to cholesterol (CHOL) in the pellet. Control groups were treated with CHOL containing pellets. Blood samples were collected in the morning and afternoon the day before and 1, 2, 5, 8, 11 and 14 days after pellet implantation. The concentrations of E2, P4 and LH were measured by RIA. Throughout the sampling period, plasma concentrations of both steroids were proportional to pellet composition. On days 1 and 2, high concentrations of E2 and P4 in plasma were obtained, but between days 5 and 14 stable levels at E2 and P4 were observed. The effectiveness of chronic replacement with E2 and P4 on the negative feedback on LH secretion was assessed from morning samples and positive feedback on LH from afternoon samples. E2 implants suppressed the morning LH levels in plasma in a time and dose-dependent manner. The afternoon concentrations of LH were significantly elevated on each sampling day, except for day 1. P4 pellets had no effect on morning-afternoon difference in LH level, but low doses suppressed LH shortly after the implantation and high doses suppressed LH level after the 8th day of implantation. These results indicate that fused pellets of E2 and P4 are effective in chronically maintaining plasma E2 and P4 at levels observed during various normal and pathological reproductive states. Further, these studies indicate that E2 can stimulate afternoon hypersecretion of LH for at least 14 days in ovariectomized rats.