학술논문
Membrane estrogen receptor α signaling modulates the sensitivity to estradiol treatment in a dose- and tissue- dependent manner.
Document Type
Academic Journal
Author
Jiang Y; Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Vita Stråket 11, S-413 45, Göteborg, Sweden.; Horkeby K; Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Vita Stråket 11, S-413 45, Göteborg, Sweden. karin.horkeby@gu.se.; Henning P; Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Vita Stråket 11, S-413 45, Göteborg, Sweden.; Wu J; Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Vita Stråket 11, S-413 45, Göteborg, Sweden.; Lawenius L; Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Vita Stråket 11, S-413 45, Göteborg, Sweden.; Engdahl C; Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Vita Stråket 11, S-413 45, Göteborg, Sweden.; Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.; Gupta P; Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Vita Stråket 11, S-413 45, Göteborg, Sweden.; Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.; Movérare-Skrtic S; Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Vita Stråket 11, S-413 45, Göteborg, Sweden.; Nilsson KH; Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Vita Stråket 11, S-413 45, Göteborg, Sweden.; Levin E; Division of Endocrinology, Department of Medicine, University of California, Irvine, Irvine, CA, 92697, USA.; Department of Veterans Affairs Medical Center, Long Beach, Long Beach, CA, 90822, USA.; Ohlsson C; Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Vita Stråket 11, S-413 45, Göteborg, Sweden.; Department of Drug Treatment, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden.; Lagerquist MK; Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Vita Stråket 11, S-413 45, Göteborg, Sweden.
Source
Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
Subject
Language
English
Abstract
Estradiol (E2) affects both reproductive and non-reproductive tissues, and the sensitivity to different doses of E2 varies between tissues. Membrane estrogen receptor α (mERα)-initiated signaling plays a tissue-specific role in mediating E2 effects, however, it is unclear if mERα signaling modulates E2 sensitivity. To determine this, we treated ovariectomized C451A females, lacking mERα signaling, and wildtype (WT) littermates with physiological (0.05 μg/mouse/day (low); 0.6 μg/mouse/day (medium)) or supraphysiological (6 μg/mouse/day (high)) doses of E2 (17β-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 mERα 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 mERα, suggesting a protective effect of mERα signaling in this tissue against supraphysiological E2 levels.
(© 2023. The Author(s).)
(© 2023. The Author(s).)