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ARS Home Plains Area Grand Forks, North Dakota Grand Forks Human Nutrition Research Center Dietary Prevention of Obesity-related Disease Research Research Publications at this Location





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Title:   Author  item
                                            ZHU, LING-LING - Mount Sinai School Of Medicineitem
                                            BLAIR, HARRY - University Of Pittsburgh Medical Centeritem
                                            Cao, Jayitem
                                            YUEN, TONY - Mount Sinai School Of Medicineitem
                                            LATIF, RAUF - Mount Sinai School Of Medicineitem
                                            GUO, LIDA - University Of Pittsburgh Medical Centeritem
                                            TOURKOVA, IRINA - University Of Pittsburgh Medical Centeritem
                                            LI, JIANHUA - Mount Sinai School Of Medicineitem
                                            DAVIES, TERRY - Mount Sinai School Of Medicineitem
                                            SUN, LI - Mount Sinai School Of Medicineitem
                                            BIAN, ZHUAN - Wuhan Universityitem
                                            ROSEN, CLIFFORD - Maine Medical Center Research Institute (MMCRI)item
                                            ZALLONE, ALBERTA - University Of Bariitem
                                            NEW, MARIA - Mount Sinai School Of Medicineitem
                                            ZAIDI, MONE - Mount Sinai School Of Medicine
  Submitted to: Proceedings of the National Academy of Sciences (PNAS)
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 7/25/2012
                                    Publication  Date: 8/20/2012
                                    Citation: Zhu, L., Blair, H.C., Cao, J.J., Yuen, T., Latif, R., Guo, L., Tourkova, I.L., Li, J., Davies, T.F., Sun, L., Bian, Z., Rosen, C., Zallone, A., New, M.I., Zaidi, M. 2012. Blocking antibody to the beta-subunit of FSH prevents bone loss by inhibiting bone resorption and stimulating bone synthesis. Proceedings of the National Academy of Sciences. 109(36):14574-14579.Interpretive Summary: Hyperthyroidism is accompanied by worsening osteoporosis. Elevated thyroid hormone levels are a major contributor of the bone loss in hyperthyroidism. Serum thyroid hormone suppresses the production of thyroid stimulating hormone (TSH). TSH is low in hyperthyroid states and directly affects bone metabolism. Mice lacking the TSH receptor (TSHR) have significant bone loss. We show that TSHR-deficient mice have greater bone loss in hyperthyroid state than wild type controls. Our data suggest that TSH plays an important role in bone metabolism.
                                Technical Abstract: Low estrogen levels undoubtedly underlie menopausal bone thinning. However, rapid and profuse bone loss begins three years prior to the last menstrual period, when serum estrogen is relatively normal. We have shown that the pituitary hormone FSH, the levels of which are high during the late peri-menopause, directly stimulates bone resorption by osteoclasts. Here, we generated and characterized a polyclonal antibody to a 13 amino acid long peptide sequence within the receptor-binding domain of the FSH beta-subunit. We show that the FSH antibody binds FSH specifically and blocks its action on osteoclast formation in vitro. When injected into ovariectomized mice, the FSH antibody attenuates bone loss significantly not only by inhibiting bone resorption, but also by stimulating bone formation, a yet uncharacterized action of FSH that we report herein. Mesenchymal cells isolated from mice treated with the FSH antibody show greater osteoblast precursor colony counts, similarly to mesenchymal cells isolated from FSHR-/- mice. This suggests that FSH negatively regulates osteoblast number. We confirm that this action is mediated by signaling-efficient FSHRs present on mesenchymal stem cells. Overall, the data prompt the future development of an FSH-blocking agent as a means of uncoupling bone formation and bone resorption to a therapeutic advantage in humans.


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