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

ABSTRACT: Estrogen receptor ? (ER?) signaling leads to cellular responses in several tissues and in addition to nuclear ER?-mediated effects, membrane ER? (mER?) signaling may be of importance. To elucidate the significance, in vivo, of mER? signaling in multiple estrogen-responsive tissues, we have used female mice lacking the ability to localize ER? to the membrane due to a point mutation in the palmitoylation site (C451A), so called Nuclear-Only-ER (NOER) mice. Interestingly, the role of mER? 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 mER? (<35% reduction in estrogen response in NOER mice). In conclusion, mER? signaling is important for the estrogenic response in female mice in a tissue-dependent manner. Increased knowledge regarding membrane initiated ER? actions may provide means to develop new selective estrogen receptor modulators with improved profiles.

SUBMITTER: Gustafsson KL 

PROVIDER: S-EPMC4937452 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature