title: Complex effects of 17β-estradiol on mitochondrial function.
abstract: Existing literature on estradiol indicates that it affects mitochondrial functions at low micromolar concentrations. Particularly blockade of the permeability transition pore (PTP) or modulation of the enzymatic activity of one or more complexes of the respiratory chain were suspicious. We prepared mitoplasts from rat liver mitochondria (RLM) to study by single-channel patch-clamp techniques the PTP, and from rat astrocytes to study the potassium BK-channel said to modulate the PTP. Additionally, we measured respiration of intact RLM. After application of 17β-estradiol (βE) our single-channel results reveal a transient increase of activity of both, the BK-channel and the PTP followed by their powerful inhibition. Respiration measurements demonstrate inhibition of the Ca(2+)-induced permeability transition, as well, though only at higher concentrations (≥30μM). At lower concentrations, we observed an increase of endogenous- and state 2-respiration. Furthermore, we show that βE diminishes the phosphorylating respiration supported by complex I-substrates (glutamate/malate) or by the complex II-substrate succinate. Taken together the results suggest that βE affects mitochondria by several modes, including partial inhibition of the activities of ion channels of the inner membrane and of respiration. This article is part of a Special Issue entitled: 17th European Bioenergetics Conference (EBEC 2012).
authors.affiliation: Dept. of Neurology, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany.
authors.forename: Anika
authors.initials: A
authors.lastname: Thiede
authors.forename: Frank Norbert
authors.initials: FN
authors.lastname: Gellerich
authors.forename: Peter
authors.initials: P
authors.lastname: Schönfeld
authors.forename: Detlef
authors.initials: D
authors.lastname: Siemen
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D010101:Oxygen Consumption / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats
chemical_list: D004967:Estrogens; D051036:Large-Conductance Calcium-Activated Potassium Channels; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D004958:Estradiol; D002118:Calcium