Estrogen and androgen play distinct roles in bone turnover in male mice before and after reaching sexual maturity

Aromatase is the sole enzyme which converts androgen into estrogen. We have reported that aromatase-knockout (ArKO) mice showed bone loss by increased bone resorption not only in female but also in male mice, suggesting essential roles of estrogen in bone metabolism in both sexes. However, loss of testicular androgen by orchidectomy (ORX) could induce bone loss in male mice. To clarify the relationship between estrogen and androgen in bone metabolism in male mice, 7-week-old ArKO mice were orchidectomized (ORX) to induce a double deficiency of estrogen and androgen. Bone loss in ORX/ArKO mice was more severe than that in ORX/wild-type and sham/ArKO mice because of advanced bone resorption, indicating that androgen and estrogen individually regulate bone mass by suppressing bone resorption in male mice after reaching sexual maturity. Cortical bone formation was elevated in sham/ArKO mice, but ORX did not influence cortical bone formation in the adult male mice. To examine the influence of androgen deficiency in weaning stage, 3-week-old wild-type mice were orchidectomized. Four weeks after operation, periosteal bone formation in the femur was markedly reduced in ORX mice. Since cortical bone in the same age of ArKO mice was normal, testicular androgen is indispensable for cortical bone formation especially at puberty in male mice. Therefore, estrogen and androgen may play distinct roles in bone turnover of male mice before and after reaching sexual maturity.