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The role of membrane ERα signaling in bone and other major estrogen responsive tissues.

  • Author(s): Gustafsson, KL;
  • Farman, H;
  • Henning, P;
  • Lionikaite, V;
  • Movérare-Skrtic, S;
  • Wu, J;
  • Ryberg, H;
  • Koskela, A;
  • Gustafsson, J-Å;
  • Tuukkanen, J;
  • Levin, ER;
  • Ohlsson, C;
  • Lagerquist, MK
  • et al.

Published Web Location

https://doi.org/10.1038/srep29473
Abstract

Estrogen receptor α (ERα) signaling leads to cellular responses in several tissues and in addition to nuclear ERα-mediated effects, membrane ERα (mERα) signaling may be of importance. To elucidate the significance, in vivo, of mERα signaling in multiple estrogen-responsive tissues, we have used female mice lacking the ability to localize ERα to the membrane due to a point mutation in the palmitoylation site (C451A), so called Nuclear-Only-ER (NOER) mice. Interestingly, the role of mERα signaling for the estrogen response was highly tissue-dependent, with trabecular bone in the axial skeleton being strongly dependent (>80% reduction in estrogen response in NOER mice), cortical and trabecular bone in long bones, as well as uterus and thymus being partly dependent (40-70% reduction in estrogen response in NOER mice) and effects on liver weight and total body fat mass being essentially independent of mERα (<35% reduction in estrogen response in NOER mice). In conclusion, mERα signaling is important for the estrogenic response in female mice in a tissue-dependent manner. Increased knowledge regarding membrane initiated ERα actions may provide means to develop new selective estrogen receptor modulators with improved profiles.

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