Details

Autor(en) / Beteiligte

• Pendaries, C.
• Darblade, B.
• Rochaix, P.
• Krust, A.
• Chambon, P.
• Korach, K. S.
• Bayard, F.
• J.-F. Arnal

Titel

The AF-1 Activation-Function of ERα May Be Dispensable to Mediate the Effect of Estradiol on Endothelial NO Production in Mice

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2002-02, Vol.99 (4), p.2205-2210

Ort / Verlag

National Academy of Sciences

Erscheinungsjahr

2002

Quelle

Elektronische Zeitschriftenbibliothek (Open access)

Beschreibungen/Notizen

• Two isoforms of estrogen receptor (ER) have been described: ERα and ERβ. The initial gene targeting of ERα, consisting in the introduction of a Neo cassette in exon 1 [αERKO, hereafter called ERα-Neo KO (knockout)], was reported in 1993. More recently, another mouse deficient in ERα because of the deletion of exon 2 (ERαKO, hereafter called ERα-Δ2 KO) was generated. In ovariectomized ERα-wild-type mice, estradiol (E2)increases uterine weight and basal production of endothelial nitric oxide (NO). Both of these effects are abolished in ERα-Δ2 KO mice. In contrast, we show here that both of these effects of E2are partially (uterine weight) or totally (endothelial NO production) preserved in ERα-Neo KO. We also confirm the presence of two ERα mRNA splice variants in uterus and aorta from ERα-Neo KO mice. One of them encodes a chimeric ERα protein (ERα55), partially deleted in the A/B domain, that was detected in both uterus and aorta by Western blot analysis. The other ERα mRNA splice variant codes for an isoform deleted for the A/B domain (ERα46), which was detected in uterus of ERα-Neo KO, and wild-type mice. This protein isoform was not detected in aorta. The identification of these two N-terminal modified isoforms in uterus, and at least one of them in aorta, probably explains the persistence of the E2effects in ERα-Neo KO mice. Furthermore, ERα-Neo KO mice may help in the elucidation of the specific functions of full-length ERα (ERα66) and ERα46, both shown to be physiologically generated in vivo.