Meeting Abstract

P3.144  Jan. 6  Steroid Sulfatase in Xenopus laevis: Characterization and inhibition. SELCER, KW*; FINNEGAN, D; Duquesne University; Duquesne University selcer@duq.edu

Steroid hormones are often conjugated to a sulfate moiety in the 3-position. The addition of a sulfate group to the steroid backbone is catalyzed by an enzyme called steroid sulfotransferase. In contrast, the enzyme steroid sulfatase removes the sulfate group from the conjugated steroids. The physiological significance of the addition and removal of the sulfate group from steroids is poorly understood, but there are indications that sulfated estrogens may be used as substrates for estrogen-dependent cancers in mammals. Inhibitors of steroid sulfatase, therefore, may be important agents for cancer therapies. Consequently, our lab and others have developed inhibitors of steroid sulfatase. One potent inhibitor is a steroidal compound called estrone sulfamate (EMATE). Another potent inhibitor that our lab has developed is a nonsteroidal compound named (p-O-sulfamoyl)-N-tetradecanoyl tyramine (DU-14). These compounds have been shown to be effective at inhibiting steroid sulfatase in several mammalian systems. However, little is known about steroid sulfatases in nonmammalian systems. We sought to determine if a steroid sulfatase enzyme was present in the liver of the frog, Xenopus laevis, and to assess whether inhibitors of this enyme developed for mammals would work in frogs. Frog liver microsomes were prepared and tested for steroid sulfatase activity using tritiated substrate conversion assays. Frog liver microsomes were able to convert 3H-estrone sulfate and 3H-dehydroepiandrosterone sulfate to their respective unsulfated counterparts, indicating the presence of a steroid sulfatase enzyme. Steroid sulfatase activity in frog microsomes was substantially inhibited by EMATE and by DU-14. These data indicate that inhibitors of mammalian steroid sulfatases are effective at inhibiting amphibian steroid sulfatase. These inhibitors could be useful for studies of the role of steroid sulfatases in amphibian physiology.