Gene expression pattern Expression of estrogen receptor alpha and beta during mouse embryogenesis

AbstractIn adult mammals numerous target tissues and organs for estrogens exist. Little is known about possible target organs during embry-ogenesis other than the reproductive tract and the gonads. This is the first report on the expression of estrogen receptor beta (ERb)incomparison with ERamRNA during mouse embryogenesis. We found expression of estrogen receptor mRNA in the reproductive tract, butalso in the atrial wall, brain, kidney, urethra, bladder neck, mammary gland primordium, midgut, cartilage primordia and perichondria. 1999 Elsevier Science Ireland Ltd. All rights reserved.Keywords: Estrogen receptor alpha; Estrogen receptor beta; Steroid hormone receptor; Mouse embryogenesis; Reproductive tract; Mam-mary gland; Cartilage primordia; Mu¨llerian duct; Wolffian duct; Gonad; Heart; Midgut; Larynx; Kidney 1. IntroductionEstrogens are steroid hormones that regulate femalereproductive organ development and functioning uponbinding to specific receptors. However, estrogens havemany more target tissues both in male and female verte-brates. The effects of estrogens on these targets can be verydifferent and a single compound can be an agonist in onetissue while being an antagonist in another. The recentlycloned ERb (Kuiper et al., 1996) has a different tissuedistribution than the classical estrogen receptor (ERa).Differential binding and activation of ERa and ERb byestrogenic compounds (Paech et al., 1997; Kuiper et al.,1998) may explain some of the observed tissue specificeffects. Stage specificity in estrogen action forms anotherlevel of complexity in estrogen action. Particularly ex-posure to exogenous estrogens such as diethylstilbes-trol (DES) leads to abnormalities in the offspring with noeffect in the mothers. We examined the expression patternof mRNA for both estrogen receptors during mouse em-bryogenesis using highly specific probes showing thecharacteristic differential expression patterns of ERa andERb (Fig. 1A,B) in adult ovary and uterus (Kuiper et al.,1996).No expression was found in embryonic day 7.5 (E7.5)and E8.5 mouse embryos (not shown and Fig. 1C) but atthis time the decidua was positive for ERa. In the re-productive tract the earliest detectable ER expressionoccurred at E10.5 and was confined to ERb expression inthe mesenchyme surrounding the mesonephric tubuli andmesonephric (Wolffian) duct of both sexes (Fig. 1D,Table 1). At this latter site ERa takes over ERb expressionfrom E12.5 until E16.5 in male but only until E14.5 infemale embryos (Fig. 1E,F,H,I and not shown), ERbexpres-