The AF-1 activation-function of ERalpha may be dispensable to mediate the effect of estradiol on endothelial NO production in mice - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2002

The AF-1 activation-function of ERalpha may be dispensable to mediate the effect of estradiol on endothelial NO production in mice

Résumé

Two isoforms of estrogen receptor (ER) have been described: ERalpha and ERbeta. The initial gene targeting of ERalpha, consisting in the introduction of a Neo cassette in exon 1 [alphaERKO, hereafter called ERalpha-Neo KO (knockout)], was reported in 1993. More recently, another mouse deficient in ERalpha because of the deletion of exon 2 (ERalphaKO, hereafter called ERalpha-delta2 KO) was generated. In ovariectomized ERalpha-wild-type mice, estradiol (E(2)) increases uterine weight and basal production of endothelial nitric oxide (NO). Both of these effects are abolished in ERalpha-delta2 KO mice. In contrast, we show here that both of these effects of E(2) are partially (uterine weight) or totally (endothelial NO production) preserved in ERalpha-Neo KO. We also confirm the presence of two ERalpha mRNA splice variants in uterus and aorta from ERalpha-Neo KO mice. One of them encodes a chimeric ERalpha protein (ERalpha55), partially deleted in the A/B domain, that was detected in both uterus and aorta by Western blot analysis. The other ERalpha mRNA splice variant codes for an isoform deleted for the A/B domain (ERalpha46), which was detected in uterus of ERalpha-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 E(2) effects in ERalpha-Neo KO mice. Furthermore, ERalpha-Neo KO mice may help in the elucidation of the specific functions of full-length ERalpha (ERalpha66) and ERalpha46, both shown to be physiologically generated in vivo.

Dates et versions

hal-04145146 , version 1 (28-06-2023)

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Citer

C. Pendaries, B. Darblade, P. Rochaix, Andree Krust, Pierre Chambon, et al.. The AF-1 activation-function of ERalpha may be dispensable to mediate the effect of estradiol on endothelial NO production in mice. Proceedings of the National Academy of Sciences of the United States of America, 2002, 99 (4), pp.2205-2210. ⟨10.1073/pnas.042688499⟩. ⟨hal-04145146⟩
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