Mechanism of catechol estrogen formation in man

Following the administration of estrone- ³H-sulfate-³⁵S to man, estrone sulfate, 2-methoxyestrone sulfate and 2-hydroxyestrone-2-sulfate were isolated from urine and purified. Their isotope content showed that estrone sulfate and 2-methoxyestrone sulfate retained 23 and 21% of the originally present ³⁵S, while 2-hydroxyestrone estrone-2-sulfate contained only 7%. From this it is concluded that estrone sulfate-³⁵S is directly transformed to 2-hydroxyestrone-3-sulfate which is partially O-methylated to yield 2-methoxyestrone sulfate with retention of isotope and partially converted to the 2-sulfate with loss of isotope. This represents an unique example of two successive metabolic transformations at a site adjacent to an intact sulfate ester. The demonstrated direct conversion of a phenol sulfate to an O-catechol sulfate is of particular significance.