Progesterone and estrogen regulate oxidative metabolism in brain mitochondria.
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.
Irwin
Ronald W
RW
Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Pharmaceutical Sciences Center, 1985 Zonal Avenue, Los Angeles, California 90089, USA.
Yao
Jia
J
Hamilton
Ryan T
RT
Cadenas
Enrique
E
Brinton
Roberta Diaz
RD
Nilsen
Jon
J
D000818:Animals; D001921:Brain / Q000378:metabolism*; D003576:Electron Transport Complex IV / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D010052:Ovariectomy; D010101:Oxygen Consumption / Q000187:drug effects*; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D005609:Free Radicals; D011374:Progesterone; D004958:Estradiol; D006861:Hydrogen Peroxide; D003576:Electron Transport Complex IV