Cited by 289Mitochondrial Function and PathologyEstrogen and related hormone effectsReproductive Biology and Fertility

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Progesterone and Estrogen Regulate Oxidative Metabolism in Brain Mitochondria

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Irwin, Ronald W., Yao, Jia, Hamilton, Ryan T., Cadenas, Enrique, Brinton, Roberta Diaz, Nilsen, Jon·2008·Endocrinology

DOI 10.1210/en.2007-1227PMC PMC2408802

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Abstract

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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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
ORCID: Yao, Jia
Cadenas, Enrique
Nilsen, Jon
Venue: Endocrinology
Publisher: The Endocrine Society
Published: 2008-02-21
Volume: 149
Issue: 6
Pages: 3167-3175
ISSN: 0013-7227 (ISSN-L)
1945-7170
DOI: 10.1210/en.2007-1227
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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Progesterone and Estrogen Regulate Oxidative Metabolism in Brain Mitochondria

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