Isoflavonoid-based bone-sparing treatments exert a low activity on reproductive organs and on hepatic metabolism of estradiol in ovariectomized rats

Autor: Raymond Berges, Marie-Jeanne Davicco, Pascal Phrakonkham, Yves Artur, Catherine Bennetau-Pelissero, Catherine Desmetz, Marie-Chantal Canivenc-Lavier, Véronique Coxam, Marie-France Pinnert, Emmanuel Jover, Joëlle Chevalier
Přispěvatelé: FLAveur, VIsion et Comportement du consommateur (FLAVIC), Etablissement National d'Enseignement Supérieur Agronomique de Dijon (ENESAD)-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), Département Neurotransmission et sécrétion neuroendocrine, Centre National de la Recherche Scientifique (CNRS), Unité de Nutrition Humaine (UNH), Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Institut National de la Recherche Agronomique (INRA), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB), Institut des Neurosciences Cellulaires et Intégratives (INCI), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université
Jazyk: angličtina
Rok vydání: 2007
Předmět:
Genistein
Estrogen receptor
Toxicology
chemistry.chemical_compound
0302 clinical medicine
Cytochrome P-450 Enzyme System
Bone Density
[SDV.IDA]Life Sciences [q-bio]/Food engineering
ESTROGEN RECEPTORS
0303 health sciences
Estradiol
food and beverages
Organ Size
Equol
3. Good health
CYTOCHROME P450
SOY ISOFLAVONE
Hormone receptor
030220 oncology & carcinogenesis
Vagina
Microsomes
Liver
Female
Menopause
EQUOL
medicine.medical_specialty
medicine.drug_class
Ovariectomy
Phytoestrogens
Biology
03 medical and health sciences
Proliferating Cell Nuclear Antigen
Internal medicine
medicine
UTEROTROPHY
Animals
[SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering
Rats
Wistar
030304 developmental biology
Pharmacology
Uterus
Daidzein
Isoflavones
Rats
Disease Models
Animal
Endocrinology
Gene Expression Regulation
chemistry
Estrogen
ESTRADIOL METABOLISM
Osteoporosis
Steroid hormone metabolism
Zdroj: Toxicology and Applied Pharmacology
Toxicology and Applied Pharmacology, Elsevier, 2007, 224 (2), pp.105-115. ⟨10.1016/j.taap.2007.06.012⟩
Toxicology and Applied Pharmacology, 2007, 224 (2), pp.105-115. ⟨10.1016/j.taap.2007.06.012⟩
ISSN: 0041-008X
1096-0333
DOI: 10.1016/j.taap.2007.06.012⟩
Popis: International audience; The use of soy isoflavones is a potential alternative to hormone replacement therapy in post-menopausal bone-loss prevention. Nevertheless, phytoestrogens can target other organs and may disrupt cell proliferation, or could modify endogenous steroid hormone metabolism. These mechanisms could be linked to an increased risk of developing cancer. We therefore studied the possible side effects of such treatments in an experimental model of menopause. Forty adult female Wistar rats were ovariectomized and fed with a genistein-, daidzein- or equol-supplemented diet at bone-sparing levels (10 mg/kg BW/day) for 3 months. The estrogenic effects were assessed by histological and molecular analyses on reproductive organs. The impact on the oxidative metabolism of estradiol and on associated cytochrome P450 (CYP) activities was evaluated in liver microsomes. The relative wet weights of both the uterus and the vagina were increased in the equol group, but no significant changes in proliferating cell nuclear antigen or hormone receptor mRNA expression were noticed. In contrast, genistein and daidzein did not induce uterotrophy but caused an overexpression of estrogen receptor α mRNA which could correspond to a long-lasting effect of physiological concentrations of estrogens. The hepatic metabolism of estradiol was influenced by daidzein which increased the synthesis of putative mutagenic derivatives. At the same time, genistein favored estrogen 2-hydroxylation, and equol decreased 4-hydroxyestrogen production. Surprisingly, no significant alteration in hepatic CYP activities was detected. Taken together, these results demonstrate that isoflavonoid-based bone-sparing treatments are able to cause side effects on other estrogen-sensitive target organs when given in the long-term.
Databáze: OpenAIRE
Externí odkaz: