Many breast tumors are hormone dependent, and there is evidence that hydrolysis of estrone sulfate (EIS) to estrone, by estrone sulfatase, is an important source of the estrogen which is found in tumors. In this study, we have developed a novel pathway for the synthesis of estrone-3-methylthiophosphonate (EI-3-MTP) and examined its ability to inhibit estrone suifatase activity in MCF-7 breast c...

We have isolated several cDNA clones from a lambda gt11 expression library by screening with antibodies prepared against the microsomal enzyme steroid sulfatase, which is deficient in classical X-chromosome-linked ichthyosis patients. One of these clones (p422) has been assigned by mapping with a somatic cell hybrid panel and by in situ hybridization to Xp22.3. Clone p422 therefore has a coinci...

The extragonadal synthesis of biological active steroid hormones from their inactive precursors in target tissues is named "intracrinology." Of particular importance for the progression of estrogen-dependent cancers is the in situ formation of the biological most active estrogen, 17beta-estradiol (E2). In cancer cells, conversion of inactive steroid hormone precursors to E2 is accomplished from...

Schwann cell (SC) transplantation following spinal cord injury (SCI) may have therapeutic potential. Functional recovery is limited however, due to poor SC interactions with host astrocytes and the induction of astrogliosis. Olfactory ensheathing cells (OECs) are closely related to SCs, but intermix more readily with astrocytes in culture and induce less astrogliosis. We previously demonstrated...

I N previous publications from this laboratory, we have described two loci, called cys-3 and eth-lr, that control a family of enzymes of sulfur anabolism in Neurospora ( MARZLUF and METZENBERG 1968; METZENBERG 1968). These could be viewed as regulatory genes in search of a locus to control, since no proven structural mutants for any of the regulated enzymes were available. KERR and FLAVIN (1970...

We report a new assay of N-acetylgalactosamine-4-sulfatase (aryl sulfatase B) activity in dried blood spots (DBS) for the early detection of mucopolysaccharidosis VI (Maroteaux-Lamy syndrome) in newborn screening. The assay uses a synthetic substrate consisting of N-acetylgalactosamine-4-sulfate moiety glycosidically linked to a hydrophobic residue and furnished with a tert-butyloxycarbamido gr...

The present study describes the biological in vitro and in vivo evaluation of 2-methoxy derivatives of estrogenic inhibitors of steroid sulfatase, namely 3-sulfamoyloxy-17 -p-tert-butylbenzyl(or benzyl)-1,3,5 (10)estratrien-17 -ols. The addition of the 2-methoxy group conserves the potent inhibitory effect on steroid sulfatase activity (IC50s of 0.024 and 0.040 nM) while removing the estrogenic...

The present study describes the biological in vitro and in vivo evaluation of 2-methoxy derivatives of estrogenic inhibitors of steroid sulfatase, namely 3-sulfamoyloxy-17alpha-p-tert-butylbenzyl(or benzyl)-1,3,5 (10)-estratrien-17beta-ols. The addition of the 2-methoxy group conserves the potent inhibitory effect on steroid sulfatase activity (IC(50)s of 0.024 and 0.040 nM) while removing the ...