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In vivo inhibition of oestrone sulphatase and dehydroepiandrosterone sulphatase by oestrone‐3‐O‐sulphamate
Author(s) -
Purohit A.,
Williams G. J.,
Roberts C. J.,
Potter B. V. L.,
Reed M. J.
Publication year - 1995
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910630119
Subject(s) - endocrinology , medicine , in vivo , androstenediol , dehydroepiandrosterone , steroid sulfatase , chemistry , in vitro , hormone , steroid , androgen , biology , biochemistry , microbiology and biotechnology
Many tumours in endocrine‐sensitive tissues, such as the breast and endometrium, are hormone‐dependent and the hydrolysis of oestrone sulphate (EIS) to oestrone by oestrone sulphatase (EI‐STS) is a major source of oestrogen in such tumours. Oestrone‐3‐O‐sulphamate (EMATE) has been shown to be a potent EI‐STS inhibitor in vitro , and in this study its ability to inhibit enzyme activity in vivo was examined. EMATE was initially administered to female rats for 7 days, after which liver EI‐STS activity was measured. As EMATE also inhibits a related sulphatase in vitro , dehydroepiandrosterone sulphatase (DHA‐STS), its effect on the activity of this enzyme in vivo was also investigated. DHA‐STS has a pivotal role in regulating the synthesis of another steroid with potent oestrogenic properties, androstenediol. Administration of EMATE almost completely inhibited liver EI ‐STS (99%) and DHA‐STS (99%) activities and was active when given by the oral or subcutaneous routes. After a single dose of EMATE or following the cessation of multiple doses for 10 days, liver EI‐STS activity remained inhibited (>95%) for up to 7 and 10 days, respectively. Other compounds, such as 4‐hydroxytamoxifen and the “pure” anti‐oestrogen ICI 182,780, which are reported to inhibit EI‐STS activity in vitro , did not inhibit activity in vivo . In a preliminary study, EMATE, when injected over a 12‐day period, effectively reduced the growth of EI S‐stimulated nitrosomethyl‐urea‐induced mammary tumours in ovariectomised rats and inhibited tumour sulphatase activity in treated animals.