Testosterone or 17β-estradiol exposure reveals sex-specific effects on glucose and lipid metabolism in human myotubes
Open accessAbstract
Changes in sex hormone levels with aging or illness may lead to metabolic disorders. Moreover, the ratio changes in men versus women may have distinct pathological responses. Since little is known about sex hormone action on muscle metabolism, we examined the role of testosterone or 17β-estradiol (E 2 ) in metabolism and investigated whether either hormone may mediate a sex-specific effect. Myotubes from postmenopausal women and age-matched male donors were treated with 10 nM testosterone or E 2 for 4 days, and assays were performed to measure metabolic readouts, signal transduction, and mRNA expression. Testosterone and E 2 treatment enhanced insulin-stimulated glucose incorporation into glycogen and AKT phosphorylation in myotubes from female donors, highlighting a sex-specific role of sex hormone in glucose metabolism. Testosterone treatment increased palmitate oxidation in myotubes from both female and male donors, while E 2 enhanced palmitate oxidation in myotubes from male donors only. Testosterone-mediated increase in palmitate oxidation was attenuated at the presence of androgen receptor antagonist, which may indicate a role of nuclear steroid receptor in muscle lipid oxidation. Testosterone treatment increased mRNA expression of the insulin receptor substrate 2 in myotubes from male and female donors, whereas it increased mRNA expression of glycogen synthase 1 only in myotubes from male donors. E 2 treatment increased pyruvate dehydrogenase kinase 4 mRNA expression in myotubes from female donors. Thus, our data suggest that testosterone or E 2 modulates muscle glucose and lipid metabolism and may play a role in metabolism in a sex-dependent manner.
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Estrogens promote lipolysis and lipid oxidation in both humans and cultured muscle cells.
“Additional experimental work further supports the role of estrogens in promoting lipolysis and lipid oxidation in both humans and cultured muscle cells [38,39,40].”
From Carbohydrate and Fat Oxidation in Muscle Assessed with Exercise Calorimetry in 6465 Subjects (2026) · cites this paper as [40]
The Results section, “Sex hormone-mediated effects on palmitate oxidation” (page unavailable), reports that estradiol increased basal palmitate oxidation in cultured human myotubes from male donors, but not female donors. The Discussion also cites increased skeletal-muscle oxidation capacity in young men after estradiol treatment. Our copy does not report that estradiol promotes lipolysis, so it supports the lipid-oxidation part but not the full claim. (LLM, conf=0.88)
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Carbohydrate and Fat Oxidation in Muscle Assessed with Exercise Calorimetry in 6465 Subjects
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“Additional experimental work further supports the role of estrogens in promoting lipolysis and lipid oxidation in both humans and cultured muscle cells [38–40].”
- Authors
- Salehzadeh, F., Rune, A., Osler, M., & Al-Khalili, L.
- Affiliations
- Karolinska Institutet (SE)
- ORCID
- Salehzadeh, Firoozeh
- Venue
- Journal of Endocrinology
- Publisher
- Bioscientifica
- Published
- 2011-06-01
- Volume
- 210
- Issue
- 2
- Pages
- 219-229
- ISSN
- 0022-0795 (ISSN-L)
- 1479-6805
- OpenAlex
- W2166743106
- Cited by
- 66
- References
- 71
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 5 · 2023: 4 · 2022: 5 · 2021: 2 · 2020: 6 · 2019: 1 · 2018: 7 · 2017: 7 · 2016: 3 · 2015: 5 · 2014: 5 · 2013: 7 · 2012: 6
- FWCI
- 4.72
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- European Commission
- Fredrik och Ingrid Thurings Stiftelse
- Karolinska Institutet
- Knut och Alice Wallenbergs Stiftelse
- Novo Nordisk
- Vetenskapsrådet
- Svenska Läkaresällskapet
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- testosterone, estradiol, sex hormones, sex differences, skeletal muscle metabolism, glucose metabolism, lipid metabolism, insulin-stimulated glucose uptake, glycogen synthesis, Akt phosphorylation, palmitate oxidation, androgen receptor, insulin receptor substrate 2, glycogen synthase 1, PDK4, postmenopausal women, myotubes
- MeSH terms
- Cell Differentiation, Estradiol, Female, Glucose, Humans, Insulin, Male, Middle Aged, Testosterone, Muscle Fibers, Skeletal, Palmitic Acid
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