Disease relevance of STS

• Studies have shown that aberrant recombination between arrays of CRI-S232-homologous repeats flanking the steroid sulfatase ( STS ) gene results in STS deletion, which is manifested clinically as X-linked ichthyosis [1].
• In breast cancer tissues examined by laser capture microdissection/RT-PCR analyses, the mRNA for EST was localized in both carcinoma and intratumoral stromal cells, whereas that of STS was detected only in carcinoma cells [2].
• EST and STS immunoreactivity was also correlated with various clinicopathological parameters, including prognosis to examine the biological significance of these enzymes in 113 breast carcinomas [2].
• Of the 113 invasive ductal carcinomas examined in this study, EST and STS immunoreactivity was detected in 50 and 84 cases (44.2 and 74.3%), respectively [2].
• CONCLUSIONS: STS and EST are expressed and may be involved in local production and metabolism of estrogens in human prostate cancers [3].

Psychiatry related information on STS

• Identification by STS PCR screening of a microdeletion in Xp21.3-22.1 associated with non-specific mental retardation [4].
• STS 25 cells express the idiotypic (Id+) immunoglobulin (Ig) specific for the neoplastic B cells of the B-NHL patient [5].
• Does the Spiritual Transcendence Scale (STS; R. L. Piedmont, 1999) predict psychosocial outcomes from an outpatient substance abuse program [6]?
• In an attempt to demonstrate the influence of the STS on memory functions in humans, we have investigated the effects of acute administration of exogenous GRF vs. placebo on short-term memory (STM) in healthy young subjects [7].
• Frequencies of serum groups (Hp and Gc) and red cell enzyme types (PGM1, 6-PGD and ES D) were studied in 195 patients with affective disorders [8].

High impact information on STS

• We have found that these STS alterations usually involve breakpoints within highly similar sequence elements situated approximately 1.9 megabases apart on the X chromosome [9].
• Variable deletion breakpoints have been recognized at the alpha-globin and dystrophin loci, but no information is available regarding STS deletions [9].
• Exceptions in which deletions do account for the majority of observed abnormalities include the alpha-thalassemias, Duchenne muscular dystrophy, and steroid sulfatase deficiency [9].
• We have cloned and characterized the human STS X-encoded locus and a pseudogene that is present on the long arm of the Y chromosome [10].
• Human STS is a microsomal enzyme important in steroid metabolism [11].

Chemical compound and disease context of STS

• In the breast carcinoma, STS and EST are suggested to play important roles in the regulation of in situ estrogen production in the breast carcinomas [12].
• Steroid sulfatase (STS, EC 3.1.6.2) catalyzes the hydrolysis of the sulfate ester bonds of a variety of sulfated steroids, such as cholesterol, dehydroepiandrosterone, and estrone sulfate, a reaction influencing fertility and breast cancer in mammals [13].
• Large-insert clone/STS contigs in Xq11-q12, spanning deletions in patients with androgen insensitivity and mental retardation [14].
• Low maternal serum unconjugated estriol during prenatal screening as an indication of placental steroid sulfatase deficiency and X-linked ichthyosis [15].
• Expression of the estrogen-synthesizing genes aromatase, steroid sulfatase (STS) and 17beta-hydroxysteroid dehydrogenase type1 (17beta-HSD(1)) has been shown to be up-regulated in primary breast cancer tissue but their expression status in metastatic tumor tissue has yet to be determined [16].

Biological context of STS

• In the present study, we evaluated the relative abundance of STS- and EST-immunoreactive protein and mRNA expression in human aorta using immunohistochemistry and reverse transcription followed by quantitative polymerase chain reaction in addition to enzyme activity [17].
• Prior studies have shown that the STS gene escapes X-chromosome inactivation [13].
• The cytotrophoblast system may offer a new possibility to study the regulation of STS gene expression [13].
• The present study was designed to assess the existence and extent of substrate cycling between steroids and their sulfate conjugates through ARSC and SULT, and also to initiate studies of the topology of the catalytic site of ARSC in the rat liver ER [18].
• Our results indicate that substrate cycling of steroids and their sulfates does occur, and suggest that the active site of ARSC may be located within the ER membrane [18].

Anatomical context of STS

• STS expression levels were found to be significantly higher in the VSMCs obtained from female aortas with mild atherosclerotic changes than in those with severe atherosclerotic changes and in male aortas regardless of atherosclerotic changes [17].
• STS activity in freshly isolated cytotrophoblasts was low (about 17%), compared to placental tis- sue, and about 1.7-fold higher in female than in male cells [13].
• In contrast to the components of the glucose-6-phosphatase system, activity of ARSC in both intact and disrupted microsomes was substantially more resistant to protease inactivation [18].
• Studies of fibroblast clones from these females provide evidence, presented here, for differential expression of STS loci on the active and inactive X chromosome [19].
• Further evidence that the STS locus escapes inactivation is that the human inactive X chromosomes contributes STS activity to mouse-human hybrid cells [19].

Associations of STS with chemical compounds

• These findings also suggest that EST and STS plays important roles in regulation of in situ estrogen production, and EST especially is a potent prognostic factor in human breast carcinoma [20].
• Estrone sulfate (E1S) is a major circulating plasma estrogen that is converted into the biologically active estrogen, estrone (E1) by steroid sulfatase (STS) [17].
• Microsomal steroid sulfatase: interactions with cytosolic steroid sulfotransferases [18].
• In spite of its similarity with these two lysosomal sulfatases, STS does not contain mannose 6-phosphate residues and is transported to lysosomes by a mannose 6-phosphate receptor-independent mechanism [21].
• The resistance of STS toward proteinase K after translocation into microsomes suggests that most, if not all, sequences of STS are exposed at the luminal side of microsomes [21].

Physical interactions of STS

• The TDRKH gene was mapped to the Epidermal Differentiation Complex (EDC) at chromosome 1q21 by radiation hybrid mapping and STS content of genomic clones from that region [22].

Regulatory relationships of STS

• The reaction was made specific for arylsulfatase A by inhibiting arylsulfatase C activity with low pH and arylsulfatase B activity with pyrophosphate [23].
• Pharmacological inhibitors of the phosphatidylinositol 3-kinase, Akt, and PDK-1 also abrogated the retinoid-stimulated increase in steroid sulfatase activity in HL60 cells [24].

Other interactions of STS

• The revelation that CRI-S232 contains VCX offers a more precise description of the genetic etiology of X-linked ichthyosis: it results from aberrant recombination between VCX gene arrays that flank the STS locus [1].
• The final karyotype was 46,Y,der(X)t(X; Y)(p22.3; q11.2).ish der(X) (DXZ1+, KAL+, STS-, SHOX-) mat [25].
• We studied the expression of the STS gene in primary cultures of cytotrophoblasts from human term placentae and compared it with the expression of autosomally encoded placental alkaline phosphatase (PALP) and X-linked glucose-6-phosphate dehydrogenase (G6PD) [13].
• CDPX is located between 2650 and 5550 kb from Xpter, and STS is located between 7250 and 7830 kb from Xpter [26].
• It is also important to note that the status of intratumoral aromatase, 17beta-HSD type 1, EST and STS in human breast cancer tissues is variable and not necessarily correlated with each other, which suggests different potential sources of intratumoral estrogens among individual patients with breast cancer [20].

Analytical, diagnostic and therapeutic context of STS

• EST and STS immunoreactivity was detected in carcinoma cells and significantly associated with their mRNA levels (P = 0.0027 and 0.0158, respectively), as measured by RT/real-time PCR, and enzymatic activities (P = 0.0005 and 0.0089, respectively) in 35 breast carcinomas [2].
• Therefore, in this study, we examined the expression of EST and STS in 35 specimens of human breast carcinoma tissues using immunohistochemistry, reverse transcription-PCR (RT-PCR), and enzymatic assay [2].
• Western blot analysis using anti-STS antibodies was performed on patients' fibroblast extracts and revealed absence of cross-reacting material [27].
• However, some patients with the classical XLI phenotype and complete STS deficiency do not show any detectable deletions by Southern blot analysis using full-length STS cDNA as a probe [27].
• Immunoblotting experiments, performed using anti-STS polyclonal antibodies, revealed the absence of cross-reacting material to STS in all cases tested, including 4 patients without evidence of deletions [28].

References