Effects of age and soybean isoflavones on hepatic cholesterol metabolism and thyroid hormone availability in acyclic female rats.
Soy-food and its isoflavones, genistein (G) and daidzein (D), were reported to exert mild cholesterol-lowering effect, but the underlying mechanism is still unclear. In this research, first we studied age-related alterations in hepatic cholesterol metabolism of acyclic middle-aged (MA) female rats. Then we tested if purified isoflavones may prevent or reverse these changes, and whether putative changes in hepatic thyroid hormone availability may be associated with this effect. Serum and hepatic total cholesterol (TChol), bile acid and cholesterol precursors, as well as serum TSH and T4concentrations, hepatic deiodinase (Dio) 1 enzyme activity and MCT8 protein expression were determined by comparing data obtained for MA with young adult (YA) intact (IC) females. Effects of subcutaneously administered G or D (35mg/kg) to MA rats were evaluated versus vehicle-treated MA females. MA IC females were characterized by: higher (p<0.05) serum TChol, lower (p<0.05) hepatic TChol and its biosynthetic precursors, lower (p<0.05) hepatic 7α-hydroxycholesterol but elevated (p<0.05) 27- and 24-hydroxycholesterol in comparison to YA IC. Both isoflavone treatments decreased (p<0.05) hepatic 27-hydroxycholesterol, G being more effective than D, without affecting any other parameter of Chol metabolism. Only G elevated hepatic Dio1 activity (p<0.05). In conclusion, age-related hypercholesteremia was associated with lower hepatic Chol synthesis and shift from main neutral (lower 7α-hydroxycholesterol) to alternative acidic pathway (higher 27-hydroxycholesterol) of Chol degradation to bile acid. Both isoflavones lowered hepatic 27-hydroxycholesterol, which may be considered beneficial. Only G treatment increased hepatic Dio1 activity, thus indicating local increase in thyroid hormones, obviously insufficient to induce prominent cholesterol-lowering effect.
Institute for Biological Research "Siniša Stanković", University of Belgrade, Despot Stefan Blvd. 142, 11000 Belgrade, Serbia. Electronic address: brankasj@ibiss.bg.ac.rs.
Branka
B
Šošić-Jurjević
Institut für Klinische Chemie und Klinische Pharmakologie Universitätsklinikum Bonn, Sigmund-Freud-Str. 25, D-53127 Bonn, Germany.
Dieter
D
Lütjohann
Institute for Biological Research "Siniša Stanković", University of Belgrade, Despot Stefan Blvd. 142, 11000 Belgrade, Serbia.
Ivana
I
Jarić
Institute for Biological Research "Siniša Stanković", University of Belgrade, Despot Stefan Blvd. 142, 11000 Belgrade, Serbia.
Marko
M
Miler
Institute for Biological Research "Siniša Stanković", University of Belgrade, Despot Stefan Blvd. 142, 11000 Belgrade, Serbia.
Danijela
D
Vojnović Milutinović
Institute for Biological Research "Siniša Stanković", University of Belgrade, Despot Stefan Blvd. 142, 11000 Belgrade, Serbia.
Branko
B
Filipović
Institute for Biological Research "Siniša Stanković", University of Belgrade, Despot Stefan Blvd. 142, 11000 Belgrade, Serbia.
Vladimir
V
Ajdžanović
Institut für Experimentelle Endokrinologie, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, D-13353 Berlin, Germany.
Kostja
K
Renko
Institut für Experimentelle Endokrinologie, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, D-13353 Berlin, Germany.
Eva Katrin
EK
Wirth
Institute for Science Application in Agriculture, University of Belgrade, Despot Stefan Blvd. 68b, 11000 Belgrade, Serbia.
Snežana
S
Janković
Institut für Experimentelle Endokrinologie, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, D-13353 Berlin, Germany.
Josef
J
Kӧhrle
Institute for Biological Research "Siniša Stanković", University of Belgrade, Despot Stefan Blvd. 142, 11000 Belgrade, Serbia.
Verica
V
Milošević
D000375:Aging; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D005260:Female; D006888:Hydroxycholesterols / Q000097:blood* / Q000378:metabolism; D007529:Isoflavones / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D048789:Phytoestrogens / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013025:Glycine max / Q000737:chemistry; D013963:Thyroid Hormones / Q000097:blood*
D006888:Hydroxycholesterols; D007529:Isoflavones; D048789:Phytoestrogens; D013963:Thyroid Hormones
Cholesterol metabolism; Daidzein; Genistein; Isoflavones; Liver; Rats; Thyroid