MEASUREMENT OF ESTRONE SULFATASE ACTIVITY IN WHITE BLOOD-CELLS TO MONITOR IN-VIVO INHIBITION OF STEROID SULFATASE ACTIVITY BY ESTRONE-3-O-SULFAMATE

Formation of oestrone via the sulphatase pathway is considered to be a major source of the oestrogen present in breast tumours. Several inhi bitors of steroid sulphatase have now been developed for use in the tr eatment of postmenopausal women with breast cancer. In order to be abl e to monitor the extent and duration of the inhibition of oestrone sul phatase (E1-STS) readily, we have developed a method to measure the ac tivity of this enzyme in white blood cells (WBCs). Hydrolysis of oestr one sulphate by E1-STS in WBCs was linear with respect to time and the volume of WBCs used. To examine whether the extent of inhibition, of E1-STS activity in WBCs, by the inhibitor oestrone-3-O-sulphamate (EMA TE), reflected inhibition in other body tissues, activity in WBCs was compared with that in liver and spleen tissue samples from rats. Two h ours after an oral dose of EMATE the extent of inhibition of E1-STS de tected in WBCs was the same as in the liver. The duration of the inhib ition of E1-STS by EMATE, examined over a 1-28 day period in rats, was similar whether monitored in WBCs, liver or spleen. Measurements of E 1-STS activity in WBCs were also used to examine the effectiveness of EMATE (0.5 mg/kg) in two male volunteers. E1-STS activity was rapidly inhibited and had only recovered by 27% after 1 month. A marked decrea se in the ratio of plasma droepiandrosterone:dehydroepiandrosterone-su lphate (DHA:DHA-S) concentrations was also detected, confirming that E MATE also inhibits DHA-STS activity. The ability to monitor the extent and duration of steroid sulphatase inhibition in WBCs will facilitate the evaluation of this new form of endocrine therapy in women with br east cancer. (C) 1997 Elsevier Science Ltd. All rights reserved.