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 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 [125 I] 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 +) (3) ovariectomized (OVX) hCG + model. Male LuRKO mice showed a decrease in BMD after 5 months, apparently secondary to suppressed gonadal steroid production. Similarly, 9-10 week 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 + mice indicating that chronic exposure to hCG results in bone formation or a decrease in bone resorption. However, OVX of the hCG + mice resulted in a significant reduction in BMD comparable to OVX wild-type controls. Although gonadotropin levels are tightly linked to sex steroid titers it appears that their effects on the skeleton are indirect.