Estrogen receptor-α and -β and aromatase knockout effects on lower limb muscle mass and contractile function in female mice
Open accessAbstract
Estrogen (E 2) is reported to regulate skeletal muscle mass and contractile function; whether E 2 exerts its effects through estrogen receptor-α (ERα) or -β (ERβ) is unclear. We determined the effect of ERα or ERβ elimination on muscle mass and contractile function in multiple muscles of the lower limb, muscles with different locomotor tasks and proportions of fiber types I and II: soleus (Sol), plantaris (Plan), tibialis anterior (TA), and gastrocnemius (Gast) in mature female mice. To determine E 2 elimination effects on muscle, we also used aromatase (Ar) knockout (KO) and wild-type (WT) mice. ERα and ArKO body weights were ∼10 and 20% higher than WT. Although muscle mass tended to show a commensurate increase in both groups, only the TA was significantly larger in ERα ( P < 0.05). Ratios of muscle mass to body mass revealed significantly lower values for Gast and TA in ArKO mice ( P < 0.05). Tetanic tension (P o) per calculated anatomical cross-sectional area (aCSA) in ERα KO was lower in TA and Gast than in WT. Lower P o/aCSA in ERα KO Gast and TA was also supported histologically by significantly less P o/fiber areas ( P < 0.05). ArKO mice also had lower P o/aCSA in Gast and TA compared with WT. ERβ KO and WT mice were comparable in all measures. Our results support the hypothesis that E 2 effects on skeletal muscle are mediated in part via the ERα but that E 2 effects may be mediated via more than one mechanism or receptor.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Skeletal muscle expresses two forms of ERs (α and β), and the effects of estrogen are mediated, in part, through these receptors.
“Skeletal muscle expresses two forms of ERs (α and β), and the effects of estrogen are mediated, in part, through these receptors (14, 21, 56, 98).”
From Sex-Based Differences in Skeletal Muscle Kinetics and Fiber-Type Composition (2015) · cites this paper as [14]
ERα-null mice have decreased tetanic tension of gastrocnemius and TA muscles in females compared with wild-type controls.
“ERα-null mice have decreased tetanic tension of gastrocnemius and TA muscles in females compared with wild-type controls (14).”
From Sex-Based Differences in Skeletal Muscle Kinetics and Fiber-Type Composition (2015) · cites this paper as [14]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Estrogen Receptor Null Mice: What Have We Learned and Where Will They Lead Us?
Couse, J. F., & Korach, K. S. (1999) · Endocrine Reviews · doi:10.1210/edrv.20.3.0370 · Cited by 2,045 · see citing works
Lubahn, D. B., Moyer, J. S., GOLDING, T. S., Couse, J. F., Korach, K. S., & Smithies, O. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.23.11162 · Cited by 1,901 · see citing works
Self-citationGeneration and reproductive phenotypes of mice lacking estrogen receptor β
Krege, J. H., Hodgin, J. B., Couse, J. F., Enmark, E., Warner, M. N., Mahler, J. F., Sar, M., Korach, K. S., Gustafsson, J.-Α., & Smithies, O. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.26.15677 · Cited by 1,692 · see citing works
Molecular diversity of myofibrillar proteins: gene regulation and functional significance
Schiaffino, S., & Reggiani, C. (1996) · Physiological Reviews · doi:10.1152/physrev.1996.76.2.371 · Cited by 1,545 · see citing works
Normal growth and development in the absence of hepatic insulin-like growth factor I
Yakar, S., Liu, J., STANNARD, B. S., Butler, A. A., Accili, D., Sauer, B., & LeRoith, D. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.13.7324 · Cited by 1,418 · see citing works
Increased adipose tissue in male and female estrogen receptor-α knockout mice
Heine, P. A., Taylor, J. A., Iwamoto, G. A., Lubahn, D. B., & Cooke, P. S. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.23.12729 · Cited by 1,282 · see citing works
Self-citationAdvances in Male Contraception
Page, S. T., Amory, J. K., & Bremner, W. J. (2008) · Endocrine Reviews · doi:10.1210/er.2007-0041 · Cited by 1,134 · see citing works
Hall, J. M., & McDonnell, D. P. (1999) · Endocrinology · doi:10.1210/endo.140.12.7179 · Cited by 1,078 · see citing works
Dupont, S., Krust, A., Gansmuller, A., Dierich, A., Chambon, P., & Mark, M. (2000) · Development · doi:10.1242/dev.127.19.4277 · Cited by 1,064 · see citing works
Production and Actions of Estrogens
Gruber, C. J., Tschugguel, W., Schneeberger, C., & Huber, J. C. (2002) · New England Journal of Medicine · doi:10.1056/nejmra000471 · Cited by 1,063 · see citing works
Couse, J. F., Lindzey, J., Grandien, K., Gustafsson, J.-A., & Korach, K. S. (1997) · Endocrinology · doi:10.1210/endo.138.11.5496 · Cited by 978 · see citing works
Pettersson, K., Grandien, K., Kuiper, G. G. J. M., & Gustafsson, J.-Α. (1997) · Molecular Endocrinology · doi:10.1210/mend.11.10.9989 · Cited by 599 · see citing works
Immunolocalisation of oestrogen receptor beta in human tissues
Taylor, A. H., & Al‐Azzawi, F. (2000) · Journal of Molecular Endocrinology · doi:10.1677/jme.0.0240145 · Cited by 529 · see citing works
Phillips, S. K., Rook, K. M., SIDDLE, N. C., Bruce, S., & WOLEDGE, R. C. (1993) · Clinical Science · doi:10.1042/cs0840095 · Cited by 506 · see citing works
Disruption of Sexual Behavior in Male Aromatase-Deficient Mice Lacking Exons 1 and 2 of thecyp19Gene
Honda, S., Harada, N., Ito, S., Takagi, Y., & Maeda, S. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.9672 · Cited by 290 · see citing works
Estrogen—the Good, the Bad, and the Unexpected
Simpson, E. R., Misso, M., Hewitt, K. N., Hill, R. A., Boon, W. C., Jones, M. E., Kovacic, A., Zhou, J., & Clyne, C. D. (2005) · Endocrine Reviews · doi:10.1210/er.2004-0020 · Cited by 266 · see citing works
Estrogen Receptors in Human Nontarget Tissues: Biological and Clinical Implications*
Ciocca, D. R., & Vargas-Roig, L. M. (1995) · Endocrine Reviews · doi:10.1210/edrv-16-1-35 · Cited by 259 · see citing works
MacLean, H. E., Chiu, W. S. M., Notini, A. J., Axell, A.-M., Davey, R. A., McManus, J. F., Ma, C., Plant, D. R., Lynch, G. S., & Zajac, J. D. (2008) · The FASEB Journal · doi:10.1096/fj.08-105726 · Cited by 209 · see citing works
Moran, A. L., Nelson, S. A., Landisch, R. M., Warren, G. L., & Lowe, D. A. (2007) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01305.2006 · Cited by 208 · see citing works
Estrogen Receptor Alpha mRNA in Human Skeletal Muscles
LEMOINE, S., GRANIER, P., TIFFOCHE, C., RANNOU-BEKONO, F., THIEULANT, M.-L., & DELAMARCHE, P. (2003) · Medicine & Science in Sports & Exercise · doi:10.1249/01.mss.0000053654.14410.78 · Cited by 201 · see citing works
Das, S. K., Taylor, J. A., Korach, K. S., Paria, B. C., Dey, S. K., & Lubahn, D. B. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.24.12786 · Cited by 164 · see citing works
Self-citationPfaffl, M. W., Lange, I. G., Daxenberger, A., & MEYER, H. H. D. (2001) · Apmis · doi:10.1034/j.1600-0463.2001.090503.x · Cited by 149 · see citing works
Estrogen status and skeletal muscle recovery from disuse atrophy
McClung, J. M., Davis, J. M., Wilson, M. A., Goldsmith, E. C., & Carson, J. A. (2006) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01583.2005 · Cited by 147 · see citing works
Receptor null mice reveal contrasting roles for estrogen receptor α and β in reproductive tissues
Couse, J. F., Hewitt, S. C., & Korach, K. S. (2000) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/s0960-0760(00)00105-9 · Cited by 144 · see citing works
Acute activation of ERα decreases food intake, meal size, and body weight in ovariectomized rats
Santollo, J., Wiley, M. D., & Eckel, L. A. (2007) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00385.2007 · Cited by 140 · see citing works
Curran, E. M., Berghaus, L. J., Vernetti, N. J., Saporita, A. J., Lubahn, D. B., & Estes, D. M. (2001) · Cellular Immunology · doi:10.1006/cimm.2002.1886 · Cited by 135 · see citing works
Self-citationPrevention of exercise-induced muscle membrane damage by oestradiol
Bär, P. R., Amelink, G. J., Oldenburg, B., & Blankenstein, M. A. (1988) · Life Sciences · doi:10.1016/0024-3205(88)90243-3 · Cited by 133 · see citing works
Ovariectomy prevents the recovery of atrophied gastrocnemius skeletal muscle mass
Sitnick, M., Foley, A. M., Brown, M., & Spangenburg, E. E. (2005) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00869.2005 · Cited by 128 · see citing works
Self-citationMoran, A. L., Warren, G. L., & Lowe, D. A. (2006) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01029.2005 · Cited by 123 · see citing works
Wiik, A., Glenmark, B., Ekman, M., Esbjörnsson‐Liljedahl, M., Johansson, O., Bodin, K., Enmark, E., & Jansson, E. (2003) · Acta Physiologica Scandinavica · doi:10.1046/j.0001-6772.2003.01186.x · Cited by 122 · see citing works
Difference in skeletal muscle function in males vs. females: role of estrogen receptor-β
Glenmark, B., Nilsson, M., Gao, H., Gustafsson, J.-Å., Dahlman-Wright, K., & Westerblad, H. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00098.2004 · Cited by 121 · see citing works
Influence of Estrogen on Skeletal Muscle Damage, Inflammation, and Repair
Tiidus, P. M. (2003) · Exercise and Sport Sciences Reviews · doi:10.1097/00003677-200301000-00008 · Cited by 120 · see citing works
Effects of Estrogen on Skeletal Myoblast Growth
Kahlert, S., Grohé, C., Karas, R. H., Löbbert, K., Neyses, L., & Vetter, H. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.6223 · Cited by 117 · see citing works
Effects of ovariectomy and estrogen on skeletal muscle function in growing rats
McCormick, K. M., Burns, K. L., Piccone, C. M., Gosselin, L. E., & Brazeau, G. A. (2004) · Journal of Muscle Research & Cell Motility · doi:10.1023/b:jure.0000021398.78327.39 · Cited by 102 · see citing works
Nilsson, S. V., & Gustafsson, J.-Α. (2002) · Critical Reviews in Eukaryotic Gene Expression · doi:10.1615/critreveukaryotgeneexpr.v12.i4.10 · Cited by 97 · see citing works
Update on animal models developed for analyses of estrogen receptor biological activity
Korach, K. S., Emmen, J. M. A., Walker, V. R., Hewitt, S. C., Yates, M. M., Hall, J. M., Swope, D. L., Harrell, J. C., & Couse, J. F. (2003) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/s0960-0760(03)00348-0 · Cited by 94 · see citing works
Disproportional Body Growth in Female Estrogen Receptor-α-Inactivated Mice
Vidal, O., Lindberg, M. K., Savendahl, L. S., Lubahn, D. B., Ritzén, E. M., Gustafsson, J.-Å., & Ohlsson, C. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.1711 · Cited by 88 · see citing works
Self-citationCharacterization of the cytosolic estrogen receptor in rat skeletal muscle
Dahlberg, E. (1982) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/0304-4165(82)90381-6 · Cited by 73 · see citing works
Effects of Gonadectomy and Estrogen Administration on Rat Skeletal Muscle
Kobori, M., & Yamamuro, T. (1989) · Clinical Orthopaedics and Related Research · doi:10.1097/00003086-198906000-00045 · Cited by 66 · see citing works
Long-term effects of estrogen on rat skeletal muscle
Suzuki, S., & Yamamuro, T. (1985) · Experimental Neurology · doi:10.1016/0014-4886(85)90219-5 · Cited by 62 · see citing works
Lemoine, S., Granier, P., Tiffoche, C., Berthon, P. M., Thieulant, M.-L., Carré, F., & Delamarche, P. (2002) · Acta Physiologica Scandinavica · doi:10.1046/j.1365-201x.2002.00992.x · Cited by 61 · see citing works
Evidence for estrogen receptor α and β expression in skeletal muscle of pigs
Kalbe, C., Mau, M., Wollenhaupt, K., & Rehfeldt, C. (2006) · Histochemistry and Cell Biology · doi:10.1007/s00418-006-0224-z · Cited by 61 · see citing works
Effects of ovariectomy and hindlimb unloading on skeletal muscle.
Fisher, J., Hasser, E. M., & Brown, M. (1998) · Journal of applied physiology · doi:10.1152/jappl.1998.85.4.1316 · Cited by 59 · see citing works
Self-citationLarionov, A. A., Vasyliev, D. A., Mason, J. I., Howie, A. F., Berstein, L. M., & Miller, W. R. (2003) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/s0960-0760(03)00059-1 · Cited by 58 · see citing works
Tamoxifen and oestrogen both protect the rat muscle against physiological damage
Koot, R. W., Amelink, G. J., Blankenstein, M. A., & Bär, P. R. (1991) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/0960-0760(91)90292-d · Cited by 42 · see citing works
The anabolic effect of estrogens on nitrogen metabolism of growing and finishing cattle and sheep.
Trenkle, A. H. (1976) · PubMed · Cited by 32 · see citing works
Zhang, S., Li, X., Burghardt, R. C., Smith, R., & Safe, S. H. (2005) · Journal of Molecular Endocrinology · doi:10.1677/jme.1.01858 · Cited by 30 · see citing works
Ovariectomy, hindlimb unweighting, and recovery effects on skeletal muscle in adult rats.
Brown, M., Foley, A. M., & Ferrería, J. (2005) · PubMed · Cited by 30 · see citing works
Self-citationPhilips, B. J., Ansell, P. J., Newton, L. G., et al. (2004) · Biochemistry · doi:10.1021/bi036154j · Cited by 22 · see citing works
Comparison of Effect of Oestrogen on Muscle Development of Male and Female Mice
Ihemelandu, E. C. (1981) · Cells Tissues Organs · doi:10.1159/000145442 · Cited by 21 · see citing works
Estrogen Receptor Biology and Lessons from Knockout Mice
Swope, D. L., & Korach, K. S. (2003) · Encyclopedia of Hormones · doi:10.1016/b0-12-341103-3/00092-9 · Cited by 4 · see citing works
Cooke, V. E., Carlisle, A. J., Talbot, R., et al. (2003) · British Poultry Science · doi:10.1080/713655286 · Cited by 3 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- [21]Knutsson A, Glenmark B, Bodin K, Jansson E, Enmark E. Estrogen receptor alpha and beta in human skeletal muscle (Abstract). FASEB J 16: A396, 2002. [Google Scholar]
- [46]Tayler AH, Al-Azzawi F. Immnunolocalization of estrogen receptor beta in human tissues. J Mol Endocrinol 24: 145–155, 2000. [DOI] [PubMed] [Google Scholar]
Cited by
Sorted by citations
Estrogens and androgens in skeletal physiology and pathophysiology
Almeida, M., Laurent, M. R., Dubois, V., Claessens, F., O'Brien, C. A., Bouillon, R., Vanderschueren, D., & Manolagas, S. C. (2017) · Physiological Reviews · doi:10.1152/physrev.00033.2015 · Cited by 860 · see citing works
Sex-Based Differences in Skeletal Muscle Kinetics and Fiber-Type Composition
Haizlip, K. M., Harrison, B. C., & Leinwand, L. A. (2015) · Physiology · doi:10.1152/physiol.00024.2014 · Cited by 521 · see citing works
Aging of the musculoskeletal system: How the loss of estrogen impacts muscle strength
Collins, B. C., Laakkonen, E. K., & Lowe, D. A. (2019) · Bone · doi:10.1016/j.bone.2019.03.033 · Cited by 227 · see citing works
Estrogen Regulates Estrogen Receptors and Antioxidant Gene Expression in Mouse Skeletal Muscle
Baltgalvis, K. A., Greising, S. M., Warren, G. L., & Lowe, D. A. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010164 · Cited by 192 · see citing works
Vascular dysfunction as a potential culprit of sarcopenia
Jeon, Y. K., Shin, M. J., Saini, S. K., Custodero, C., Aggarwal, M., Anton, S. D., Leeuwenburgh, C., & Mankowski, R. T. (2021) · Experimental Gerontology · doi:10.1016/j.exger.2020.111220 · Cited by 60 · see citing works
Verbrugge, S. A. J., Schönfelder, M., Becker, L., Yaghoob Nezhad, F., Hrabě de Angelis, M., & Wackerhage, H. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.00553 · Cited by 56 · see citing works
Aoyama, S., Jia, H., Nakazawa, K., Yamamura, J., Saito, K., & Kato, H. (2016) · The Journal of Nutrition · doi:10.3945/jn.115.226316 · Cited by 23 · see citing works
- Authors
- Brown, M., Ning, J., Ferreira, J. A., Bogener, J. L., & Lubahn, D. B.
- Affiliations
- University of Missouri (US)
- ORCID
- Ning, Jie
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2009-04
- Volume
- 296
- Issue
- 4
- Pages
- E854-E861
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- PMC
- PMC2670624
- OpenAlex
- W2169782763
- Cited by
- 60
- References
- 52
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 2 · 2021: 4 · 2020: 3 · 2019: 4 · 2018: 5 · 2017: 3 · 2016: 7 · 2015: 7 · 2014: 1 · 2013: 6 · 2012: 3
- FWCI
- 2.92
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Environmental Health Sciences (P01ES010535, P01 ES 10535)
- National Center for Complementary and Integrative Health (R01AT002978)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R21HD058834, HD058834)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Keywords
- estrogen receptor alpha, estrogen receptor beta, estrogen, skeletal muscle mass, muscle contractility, lower limb muscles, tibialis anterior, gastrocnemius, soleus muscle, plantaris, tetanic tension, muscle fiber composition, female mice
- MeSH terms
- Animals, Aromatase, Body Weight, Estradiol, Female, Mice, Inbred C57BL, Muscle Contraction, Muscle Proteins, Organ Size, Mice, Knockout, Muscle, Skeletal, Muscle Fibers, Skeletal, Lower Extremity, Estrogen Receptor alpha, Estrogen Receptor beta, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review