WEAK ESTROGENIC ACTIVITY FROM CONTINUOUS-RELEASE PELLETS

In the process of evaluating a proprietary compound for weak estrogeni c activity, two different types of dosing regimens were used, repeated daily dosing (three times/d) and continuous-release pellets, In studi es using the proprietary compound, rats that were dosed via intraperit oneal injection showed no estrogenic responses, while those receiving the test compound via continuous-release pellets displayed several est rogenic responses, Because of the conflicting results, the control pel lets were evaluated for estrogenic activity in the same battery of tes ts using the same number of pellets, In studies using only the control pellets, several estrogenic responses were observed including increas ed uterine weight, uterine stromal cell proliferation, estrous convers ion, uterine progesterone receptor content, and decreased uterine estr ogen receptor content, Animals receiving no pellet implant showed no e strogenic responses, In addition, a methylene chloride/DMSO extract of the control pellets promoted expression of a reporter gene controlled by the estrogen receptor and demonstrated competition with 17 beta-es tradiol for binding to the human estrogen receptor, It is concluded th at component(s) of the control pellets possess weak estrogenic activit y. (C) 1997 Elsevier Science Inc.