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Investigational Drug Potent Estrogen Antagonist in Mice

Bazedoxifene exhibits lower estrogen receptor agonist activity as well as higher antagonist activity in mouse uterus and mammary gland

MONDAY, Dec. 1 (HealthDay News) -- Compared with the conventional selective estrogen receptor modulators (SERMs) raloxifene and lasofoxifene, the investigational SERM bazedoxifene is a more potent antagonist of estrogen activity in both the uterus and mammary gland of mice, according to research published online Nov. 20 in Endocrinology.

Bryan J. Peano, of Wyeth Research in Collegeville, Pa., and colleagues compared the estrogen-dependent effects of three SERMS (bazedoxifene, raloxifene and lasofoxifene) in the mouse mammary gland. The investigators evaluated each SERM both as a single-agent and as part of a tissue selective estrogen complex in which it was partnered with a conjugated estrogen (CE). To enhance their ability to detect estrogen-dependent responses, including changes in the ductal invasion of the mammary fat pad, changes in primary branching patterns, and alterations in expression of the estrogen-responsive gene AREG in the mouse mammary gland, the researchers used sexually immature ovariectomized mice.

Bazedoxifene consistently had little to no estrogen receptor agonist activity, measured as estrogen-induced uterine wet weight increase, and in fact was statistically similar with the estrogen receptor agonist activity of the vehicle used, the report indicates. Bazedoxifene antagonist activity was evident by a decrease in gene expression of amphiregulin in the mammary gland.

"In summary, in an animal model evaluating estrogen-modulated uterine effects and mammary gland development, bazedoxifene exhibited less estrogen receptor agonist activity than raloxifene or lasofoxifene, and, as a tissue selective estrogen complex, bazedoxifene/CE demonstrated less mammary gland stimulation than raloxifene/CE and lasofoxifene/CE," the authors conclude.

All of the study authors are employees of Wyeth Research.

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