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  • Ohlsson, Claes,1965Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition (author)

The effects of estradiol are modulated in a tissue-specific manner in mice with inducible inactivation of ERα after sexual maturation.

  • Article/chapterEnglish2020

Publisher, publication year, extent ...

  • American Physiological Society,2020

Numbers

  • LIBRIS-ID:oai:gup.ub.gu.se/291782
  • https://gup.ub.gu.se/publication/291782URI
  • https://doi.org/10.1152/ajpendo.00018.2020DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:143770883URI

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  • Language:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Mouse models with lifelong inactivation of estrogen receptor α (ERα) show that ERα is the main mediator of estrogenic effects in bone, thymus, uterus, and fat. However, ERα inactivation early in life may cause developmental effects that confound the adult phenotypes. To address the specific role of adult ERα expression for estrogenic effects in bone and other non-skeletal tissues, we established a tamoxifen-inducible ERα-inactivated model by crossing CAG-Cre-ER and ERαflox/flox mice. Tamoxifen-induced ERα-inactivation after sexual maturation substantially reduced ERα mRNA levels in cortical bone, trabecular bone, thymus, uterus, gonadal fat, and hypothalamus, in CAG-Cre-ERαflox/flox (inducible ERαKO) compared to ERαflox/flox (control) mice. 17β-estradiol (E2) treatment increased trabecular bone volume fraction (BV/TV), cortical bone area and uterine weight, while it reduced thymus weight and fat mass in ovariectomized control mice. The estrogenic responses were substantially reduced in inducible ERαKO mice compared to control mice on BV/TV (-67%), uterine weight (-94%), thymus weight (-70%), and gonadal fat mass (-94%). In contrast, the estrogenic response on cortical bone area was unaffected in inducible ERαKO compared to control mice. In conclusion, using an inducible ERαKO model, not confounded by lack of ERa during development, we demonstrate that ERα expression in sexually mature female mice is required for normal E2 responses in most, but not all tissues. The finding that cortical, but not trabecular bone, responds normally to E2 treatment in inducible ERαKO mice strengthens the idea of cortical and trabecular bone being regulated by estrogen via different mechanisms.

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  • Farman, Helen H.,1983Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xfarhe (author)
  • Gustafsson, Karin L.,1987Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xlmarv (author)
  • Wu, JianyaoGothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xwujio (author)
  • Henning, Petra,1974Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xhenpe (author)
  • Windahl, Sara H,1971Karolinska Institutet,Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xwinds (author)
  • Sjögren, Klara,1970Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xsjokl (author)
  • Gustafsson, Jan-ÅkeKarolinska Institutet (author)
  • Movérare-Skrtic, SofiaGothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xmovso (author)
  • Lagerquist, MarieGothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xlmarv (author)
  • Göteborgs universitetCentre for Bone and Arthritis Research (creator_code:org_t)

Related titles

  • In:American journal of physiology. Endocrinology and metabolism: American Physiological Society318:5, s. 646-6541522-15550193-1849

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