Angiostatic steroids. Method of discovery and mechanism of action.

A new class of steroids has been found that inhibits angiogenesis in the presence of nonanticoagulant heparin. Tetrahydrocortisol is the most potent of the naturally occurring angiostatic steroids. It is a metabolite of cortisone that circulates in the blood, appears in the urine, and was previously believed to be biologically inactive. Both the plasma form and the urinary form are antiangiogenic. The mechanism of action of these steroids depends on their ability to specifically alter basement membrane turnover in growing capillary blood vessels. These steroids represent a prototype of angiogenesis inhibitors that may find potential therapeutic use as adjuncts to anticancer therapy, and in diseases dominated by abnormal neovascularization, i.e., angiogenesis-dependent diseases.