6-keto-prostaglandin E1-stimulated bone resorption in organ culture

Abstract

Previous investigations have shown that prostaglandin E₂ (PGE₂), 13,14-dihydro-PGE₂, and prostacyclin (PGI₂) are among the most potent prostaglandin stimulators of bone resorption. 6-Ketoprostaglandin F_1α (6-keto-F_1α; also called 6-oxo-prostaglandin F_1α), a metabolite of PGI₂ formed by spontaneous hydrolysis, has little bone resorptive or other biological activity. The present study demonstrated that another metabolite of PGI₂, 6-keto-prostaglandin E₁ (6-keto-PGE₁; also called 6-oxo-prostaglandin E₁), was active in stimulating bone resorption in fetal rat long bone organ culture. 6-Keto-PGE₁ stimulated significant release of previously incorporated⁴⁵Ca over the concentration range of 10⁻⁹ to 10⁻⁵ M. The potency of 6-keto-PGE₁ was one-twelfth that of PGE₂. If 6-keto-PGE₁ is formed by bone or adjacent tissues, or reaches bone through the circulation, it could significantly affect bone mineral metabolism.