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Membrane estrogen receptor alpha signaling modulates the sensitivity to estradiol treatment in a dose- and tissue- dependent manner
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- Jiang, Yiwen (författare)
- Gothenburg 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
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- Horkeby, Karin L (författare)
- Gothenburg 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
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- Henning, Petra, 1974 (författare)
- 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
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- Levin, E. (författare)
- visa färre...
- (creator_code:org_t)
- 2023
- 2023
- Engelska.
- Ingår i: Scientific Reports. - 2045-2322. ; 13:1
- Tidskriftsartikel (refereegranskat)
Abstract
Ämnesord
Stäng
- Estradiol (E2) affects both reproductive and non-reproductive tissues, and the sensitivity to different doses of E2 varies between tissues. Membrane estrogen receptor alpha (mER alpha)-initiated signaling plays a tissue-specific role in mediating E2 effects, however, it is unclear if mER alpha signaling modulates E2 sensitivity. To determine this, we treated ovariectomized C451A females, lacking mER alpha signaling, and wildtype (WT) littermates with physiological (0.05 mu g/mouse/day (low); 0.6 mu g/mouse/day (medium)) or supraphysiological (6 mu g/mouse/day (high)) doses of E2 (17 beta-estradiol-3-benzoate) for three weeks. Low-dose treatment increased uterus weight in WT, but not C451A mice, while non-reproductive tissues (gonadal fat, thymus, trabecular and cortical bone) were unaffected in both genotypes. Medium-dose treatment increased uterus weight and bone mass and decreased thymus and gonadal fat weights in WT mice. Uterus weight was also increased in C451A mice, but the response was significantly attenuated (- 85%) compared to WT mice, and no effects were triggered in non-reproductive tissues. High-dose treatment effects in thymus and trabecular bone were significantly blunted (- 34% and - 64%, respectively) in C451A compared to WT mice, and responses in cortical bone and gonadal fat were similar between genotypes. Interestingly, the high dose effect in uterus was enhanced (+ 26%) in C451A compared to WT mice. In conclusion, loss of mER alpha signaling reduces the sensitivity to physiological E2 treatment in both non-reproductive tissues and uterus. Furthermore, the E2 effect after high-dose treatment in uterus is enhanced in the absence of mER alpha, suggesting a protective effect of mER alpha signaling in this tissue against supraphysiological E2 levels.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
Nyckelord
- replacement therapy
- er-alpha
- bone
- extranuclear
- menopause
- complex
- roles
- serum
- risk
- Science & Technology - Other Topics
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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- Av författaren/redakt...
- Jiang, Yiwen
- Horkeby, Karin L
- Henning, Petra, ...
- Wu, Jianyao
- Lawenius, Lina
- Engdahl, Cecilia ...
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- Gupta, Priti
- Moverare-Skrtic, ...
- Nilsson, Karin H ...
- Levin, E.
- Ohlsson, Claes, ...
- Lagerquist, Mari ...
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