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Progesterone and Estrogen Regulate Oxidative Metabolism in Brain Mitochondria
Open accessAbstract
The ovarian hormones progesterone and estrogen have well-established neurotrophic and neuroprotective effects supporting both reproductive function and cognitive health. More recently, it has been recognized that these steroids also regulate metabolic functions sustaining the energetic demands of this neuronal activation. Underlying this metabolic control is an interpretation of signals from diverse environmental sources integrated by receptor-mediated responses converging upon mitochondrial function. In this study, to determine the effects of progesterone (P4) and 17β-estradiol (E2) on metabolic control via mitochondrial function, ovariectomized rats were treated with P4, E2, or E2 plus P4, and whole-brain mitochondria were isolated for functional assessment. Brain mitochondria from hormone-treated rats displayed enhanced functional efficiency and increased metabolic rates. The hormone-treated mitochondria exhibited increased respiratory function coupled to increased expression and activity of the electron transport chain complex IV (cytochrome c oxidase). This increased respiratory activity was coupled with a decreased rate of reactive oxygen leak and reduced lipid peroxidation representing a systematic enhancement of brain mitochondrial efficiency. As such, ovarian hormone replacement induces mitochondrial alterations in the central nervous system supporting efficient and balanced bioenergetics reducing oxidative stress and attenuating endogenous oxidative damage.
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“Estrogen and progesterone contributed to sex differences in cellular respiration and anti-oxidative functions of brain mitochondria in uninjured female rodents.”
From Sex Differences in Traumatic Brain Injury: What We Know and What We Should Know (2019) · cites this paper as [141]
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Metadata
- Authors
- Irwin, R. W., Yao, J., Hamilton, R. T., Cadenas, E., Brinton, R. D., & Nilsen, J.
- Affiliations
- University of Southern California (US)
- Department of Pharmacology and Pharmaceutical Sciences (R.W.I., J.Y., R.T.H., E.C., R.D.B., J.N.), University of Southern California, Pharmaceutical Sciences Center, University of Southern California, Los Angeles, California, 90033
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2008-02-21
- Volume
- 149
- Issue
- 6
- Pages
- 3167-3175
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- PMC
- PMC2408802
- OpenAlex
- W2069825814
- Cited by
- 289
- References
- 39
- Citations by year
- 2026: 14 · 2025: 8 · 2024: 17 · 2023: 27 · 2022: 10 · 2021: 17 · 2020: 12 · 2019: 15 · 2018: 19 · 2017: 14 · 2016: 15 · 2015: 18 · 2014: 13 · 2013: 14 · 2012: 21
- FWCI
- 7.55
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Endocrinology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (T32AG000093, T32-AG000093-24/25, P01AG026572)
- National Institute of Mental Health (R01MH067159, 1R01 MH67159-01)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Health Sciences › Medicine › Reproductive Medicine › Reproductive Biology and Fertility
- Keywords
- progesterone, estradiol, ovarian hormones, brain mitochondria, mitochondrial respiration, cytochrome c oxidase, electron transport chain, reactive oxygen species, lipid peroxidation, oxidative stress, brain energy metabolism, hormone replacement therapy, ovariectomy
- MeSH terms
- Animals, Brain, Electron Transport Complex IV, Estradiol, Female, Free Radicals, Hydrogen Peroxide, Mitochondria, Ovariectomy, Oxygen Consumption, Progesterone, Lipid Peroxidation, Rats, Sprague-Dawley, Reverse Transcriptase Polymerase Chain Reaction, Rats
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