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The bone-protective effect of genistein in the animal model of bilateral ovariectomy: roles of phytoestrogens and PTH/PTHR1 against post-menopausal osteoporosis.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2012; Vol. 13 (1), pp. 56-70. Date of Electronic Publication: 2011 Dec 22. - Publication Year :
- 2012
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Abstract
- Genistein, a major phytoestrogen of soy, is considered a potential drug for the prevention and treatment of post-menopausal osteoporosis. Mounting evidence suggested a positive correlation between genistein consumption and bone health both in vivo and in vitro. Earlier studies have revealed that genistein acted as a natural estrogen analogue which activated estrogen receptor and exerted anti-osteoporotic effect. However, it remains unclear whether PTH, the most crucial hormone that regulates mineral homeostasis, participates in the process of genistein-mediated bone protection. In the present study, we compared the therapeutic effects between genistein and nilestriol and investigated whether PTH and its specific receptor PTHR1 altered in response to genistein-containing diet in the animal model of ovariectomy. Our results showed that genistein administration significantly improved femoral mechanical properties and alleviates femoral turnover. Genistein at all doses (4.5 mg/kg, 9.0 mg/kg and 18.0 mg/kg per day, respectively) exerted improved bending strength and b-ALP limiting effects than nilestriol in the present study. However, genistein administration did not exert superior effects on bone protection than nilestriol. We also observed circulating PTH restoration in ovariectomized rats receiving genistein at the dose of 18 mg/kg per day. Meanwhile, PTHR1 abnormalities were attenuated in the presence of genistein as confirmed by RT-PCR, Western blot and immunohistochemistry. These findings strongly support the idea that besides serving as an estrogen, genistein could interact with PTH/PTHR1, causing a superior mineral restoring effect than nilestriol on certain circumstance. In conclusion, our study reported for the first time that the anti-osteoporotic effect of genistein is partly PTH/PTHR1-dependent. Genistein might be a potential option in the prevention and treatment of post-menopausal osteoporosis with good tolerance, more clinical benefits and few undesirable side effects.
- Subjects :
- Alkaline Phosphatase blood
Animals
Bone Density drug effects
Creatinine blood
Creatinine urine
Disease Models, Animal
Estriol analogs & derivatives
Estriol chemistry
Estriol pharmacology
Female
Femur physiology
Genistein chemistry
Genistein therapeutic use
Humans
Kidney metabolism
Kidney pathology
Osteoporosis, Postmenopausal metabolism
Osteoporosis, Postmenopausal pathology
Osteoporosis, Postmenopausal prevention & control
Ovariectomy
Parathyroid Hormone blood
Parathyroid Hormone urine
Phytoestrogens chemistry
Phytoestrogens therapeutic use
Protective Agents chemistry
Protective Agents therapeutic use
Quinestrol analogs & derivatives
Rats
Rats, Sprague-Dawley
Receptor, Parathyroid Hormone, Type 1 genetics
Tensile Strength
Femur drug effects
Genistein pharmacology
Parathyroid Hormone metabolism
Phytoestrogens pharmacology
Protective Agents pharmacology
Receptor, Parathyroid Hormone, Type 1 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 13
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 22312238
- Full Text :
- https://doi.org/10.3390/ijms13010056