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Int. J. Mol. Sci. 2012, 13(1), 56-70; doi:10.3390/ijms13010056

The Bone-Protective Effect of Genistein in the Animal Model of Bilateral Ovariectomy: Roles of Phytoestrogens and PTH/PTHR1 Against Post-Menopausal Osteoporosis

Received: 5 September 2011 / Revised: 13 November 2011 / Accepted: 7 December 2011 / Published: 22 December 2011
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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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.
Keywords: genistein; phytoestrogen; osteoporosis; PTH; PTHR1 genistein; phytoestrogen; osteoporosis; PTH; PTHR1
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Miao, Q.; Li, J.-G.; Miao, S.; Hu, N.; Zhang, J.; Zhang, S.; Xie, Y.-H.; Wang, J.-B.; Wang, S.-W. The Bone-Protective Effect of Genistein in the Animal Model of Bilateral Ovariectomy: Roles of Phytoestrogens and PTH/PTHR1 Against Post-Menopausal Osteoporosis. Int. J. Mol. Sci. 2012, 13, 56-70.

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Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert