Lack of effect of ovariectomy on divalent cation regulation of skeletal adenylate cyclase.

Both estrogen and androgen have been reported to attenuate cyclic AMP responses to parathyroid hormone stimulation in cultured bone cells. The present study examines the effect of in vivo estrogen deficiency on skeletal adenylate cyclase (AC) activity. The AC activity was compared in bone membranes prepared from normal female guinea pigs and from age-matched guinea pigs 3 weeks after ovariectomy. Histomorphometric analysis of femoral specimens from the ovariectomized guinea pigs demonstrated significant decreases in percentage bone volume, the percentage eroded surfaces and osteoclast numbers, and increased osteoid thickness, compared with the normal controls. No differences were found in basal AC activity, the ability of bone AC to be stimulated by parathyroid hormone (bPTH(1-34)) or isoproterenol, or in the regulation of AC activity by calcium and magnesium. We conclude that bone AC is not a direct target for estrogen effects on bone cells and that the reported effects of sex steroids on cAMP levels in bone cells probably act via an indirect mechanism.