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Mechanisms of Hormone Action |
a Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland 21201
Estrogen regulates the growth and differentiation of the uterus via binding to estrogen receptors (ERs), members of the nuclear receptor family of transcription factors. Two forms of ER exist: ER
and ERß. The former is a well-characterized mediator of estrogen-induced transcription, but the function of the latter is unclear. Recent in vitro studies suggest that both splicing forms of ERß expressed in rat tissues, ß1 and ß2, may function as inhibitors of ER
transcriptional activity. To gain insight into the role of ERß in estrogen action, we examined the effects of estrogen and relaxin, a ligand-independent activator of ERs, on the expression of ERß1 and ERß2 mRNA in the uterus in vivo. Eighteen-day-old female rats were ovariectomized and, after recovery, treated with 17ß-estradiol, relaxin, or vehicle. Quantitative reverse transcription-polymerase chain reaction analyses of uterine RNA from estrogen-treated animals revealed marked decreases in the steady-state levels of the mRNAs for both ERß1 and ERß2 at 3, 6, and 24 h after treatment. Relaxin induced a similar effect. Neither hormone had any significant effect on ER
mRNA levels. To determine if endogenous estrogen exerts this effect, we examined the expression of ERßs in the uterus during the estrous cycle. Levels of both isoforms were highest at diestrus (low estrogen), were significantly lower at early proestrus (rising estrogen), reached a nadir during late proestrus (peak estrogen), and rebounded at estrus (declining estrogen). These data suggest that down-regulation of ERß expression may be required for estrogen to exert its full trophic effects on the uterus.
2 Correspondence: Robert D. Koos, Department of Physiology, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, MD 21201-1559. FAX: 410 706 8341; rkoos{at}umaryland.edu
3 S.B.P. and J.M.J. contributed equally and should be considered co-first authors
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