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

K. L. Gustafsson, H. Farman, P. Henning, V. Lionikaite, S. Moverare-Skrtic, J. Wu, H. Ryberg, A. Koskela, J. Gustafsson, J. Tuukkanen, E. R. Levin, C. Ohlsson, M. K. Lagerquist

Research output: Contribution to journalArticle

29 Scopus citations

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.

Original languageEnglish (US)
Article number29473
JournalScientific Reports
Volume6
DOIs
StatePublished - Jul 8 2016

ASJC Scopus subject areas

  • General

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