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ß+) Have Bone Phenotypes
Department of Oral & Dental Sciences (S.J.Y., K.W., N.L.B., J.R.S., J.P.M.), Division of Child Dental Health, University of Bristol Dental School, Bristol BS1 2LY, United Kingdom; Department of Orthopaedics (M.J.P., T.J.C.), University of Bristol, Bristol BS2 8EJ, United Kingdom; and Department of Physiology (T.L., S.B.R., F.-P.Z., I.H.), University of Turku, FIN-20520 Turku, Finland
Address all correspondence and requests for reprints to: Dr. Jason P. Mansell, Division Child Dental Health, University of Bristol Dental School, Lower Maudlin Street, Bristol BS1 2LY, United Kingdom. E-mail: j.p.mansell{at}bris.ac.uk.
Considerable attention has been paid to the role of sex steroids during periods of major skeletal turnover, but the interaction of the gonadotropic hormones, which include LH, FSH, and human chorionic gonadotropin (hCG), within bone tissue have been overlooked. The question is pertinent due to the recent detection of extragonadal expression of gonadotropin receptors. Western blotting, immunolocalization, and RT-PCR supported the presence of osteoblast LH receptors. However, osteoblast cells failed to bind [125I]hCG and treatment with hCG failed to generate either cAMP or phosphorylated ERK 1/2. Bone mineral density (BMD) and bone histomorphometry were examined in the following models: 1) LH receptor null mutant (LuRKO) mice; 2) transgenic mice overexpressing hCG (hCG 
ß+); and 3) ovariectomized (OVX) hCG ß+ model. Male LuRKO mice showed a decrease in BMD after 5 months, apparently secondary to suppressed gonadal steroid production. Similarly, 9- to 10-wk-old female LuRKO mice exhibited decreases in histomorphometric parameters tested. The data indicate that loss of LH signaling results in a reduction in bone formation or an increase in bone resorption. By contrast, there were significant increases in BMD and histomorphometric indices for female, but not male, hCG ß+ mice, indicating that chronic exposure to hCG results in bone formation or a decrease in bone resorption. However, OVX of the hCG ß+ mice resulted in a significant reduction in BMD comparable to OVX WT controls. Although gonadotropin levels are tightly linked to sex steroid titers, it appears that their effects on the skeleton are indirect.
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