Ratka A, Simpkins J W
Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville 32610.
Endocr Res. 1990;16(2):165-84. doi: 10.1080/07435809009032997.
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.
将带有心房插管的去卵巢（OVX）Sprague-Dawley大鼠皮下植入含有雌二醇（E2）或孕酮（P4）的融合丸剂。通过改变丸剂中激素与胆固醇（CHOL）的比例来实现不同剂量的E2（0.1%、0.5%、1%和5%）或P4（10%、50%、75%、100%）。对照组用含CHOL的丸剂治疗。在植入丸剂前一天以及植入后1、2、5、8、11和14天的上午和下午采集血样。通过放射免疫分析法（RIA）测量E2、P4和促黄体生成素（LH）的浓度。在整个采样期间，两种类固醇的血浆浓度与丸剂组成成正比。在第1天和第2天，血浆中获得了高浓度的E2和P4，但在第5天至第14天观察到E2和P4的稳定水平。从上午的样本评估E2和P4慢性替代对LH分泌负反馈的有效性，从下午的样本评估对LH正反馈的有效性。E2植入物以时间和剂量依赖性方式抑制血浆中上午的LH水平。除第1天外，在每个采样日下午LH的浓度均显著升高。P4丸剂对LH水平的上午-下午差异没有影响，但低剂量在植入后不久抑制LH，高剂量在植入第8天后抑制LH水平。这些结果表明，E2和P4的融合丸剂能有效地将血浆E2和P4长期维持在各种正常和病理生殖状态下观察到的水平。此外，这些研究表明，E2可在去卵巢大鼠中刺激LH下午的分泌亢进至少14天。
