Progesterone and estrogen regulate oxidative metabolism in brain mitochondria.

TitleProgesterone and estrogen regulate oxidative metabolism in brain mitochondria.
Publication TypeJournal Article
Year of Publication2008
AuthorsIrwin RW, Yao J, Hamilton RT, Cadenas E, Brinton RDiaz, Nilsen J
JournalEndocrinology
Volume149
Issue6
Pagination3167-75
Date Published2008 Jun
ISSN0013-7227
KeywordsAnimals, Brain, Electron Transport Complex IV, Estradiol, Female, Free Radicals, Hydrogen Peroxide, Lipid Peroxidation, Mitochondria, Ovariectomy, Oxygen Consumption, Progesterone, Rats, Rats, Sprague-Dawley, Reverse Transcriptase Polymerase Chain Reaction
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 17beta-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.

DOI10.1210/en.2007-1227
Alternate JournalEndocrinology
PubMed ID18292191
PubMed Central IDPMC2408802
Grant ListR01 MH067159 / MH / NIMH NIH HHS / United States
1R01 MH67159-01 / MH / NIMH NIH HHS / United States
5P01AG026572 / AG / NIA NIH HHS / United States
P01 AG026572 / AG / NIA NIH HHS / United States
T32 AG000093 / AG / NIA NIH HHS / United States
T32-AG000093-24/25 / AG / NIA NIH HHS / United States
Faculty Member Reference: 
Roberta Diaz Brinton, Ph.D