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Biphasic effects of manganese on hormone-stimulated bone resorption.

Manganese, at concentrations of greater than 0.3 mM, inhibited PTH-stimulated resorption of fetal rat limb bones. At lower concentrations, 0.01 to 0.3 mM, manganese stimulated resorption. The bone resorbing effects of manganese were additive with those of PTH, prostaglandin E2, 1,25-dihydroxyvitamin D3, or isobutylmethylxanthine, but were potentiated by ionophore A23187. The stimulatory effects of manganese were inhibited by calcitonin but not by indomethacin. Manganese appeared to act intracellularly to stimulate resorption, in that the enhancing effects were also seen when the manganese was encapsulated in liposomes. Both stimulatory and inhibitory manganese concentrations increased cAMP in the culture medium. Manganese concentrations that inhibited PTH-stimulated resorption also inhibited the effect of PTH on medium cAMP. The enhancement of PTH-induced resorption by manganese was, however, not accompanied by increases in cAMP in the culture medium. This suggests that the PTH-Mn interaction is not mediated through the adenylate cyclase system.