Steroid Sulfatase Activities in Human Leukocytes: Biochemical and Clinical Aspects.

Hirato, K; Suzuki, Takasi; Hondo, Tatsuya; Saitô, Hiroshi; Yanaihara, Takumi

doi:10.1507/endocrj1954.38.597

Cited by 14 publications

(13 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The effects of DHEA might not be exerted via DHEA-specific receptors, but rather via receptors for active androgenic metabolites of DHEA-S and DHEA generated in immune cells (44). Specifically leukocytes, including macrophages, possess the sulphatases and other enzymes important in this conversion (45,46).…”

Section: Discussionmentioning

confidence: 99%

Opposing effects of dehydroepiandrosterone and dexamethasone on the generation of monocyte-derived dendritic cells

Canning

Grotenhuis

Wit

et al. 2000

European Journal of Endocrinology

View full text Add to dashboard Cite

Background: Dehydroepiandrosterone (DHEA) has been suggested as an immunostimulating steroid hormone, of which the effects on the development of dendritic cells (DC) are unknown. The effects of DHEA often oppose those of the other adrenal glucocorticoid, cortisol. Glucocorticoids (GC) are known to suppress the immune response at different levels and have recently been shown to modulate the development of DC, thereby influencing the initiation of the immune response. Variations in the duration of exposure to, and doses of, GC (particularly dexamethasone (DEX)) however, have resulted in conflicting effects on DC development. Aim: In this study, we describe the effects of a continuous high level of exposure to the adrenal steroid DHEA (10 26 M) on the generation of immature DC from monocytes, as well as the effects of the opposing steroid DEX on this development. Results: The continuous presence of DHEA (10 26 M) in GM-CSF/IL-4-induced monocyte-derived DC cultures resulted in immature DC with a morphology and functional capabilities similar to those of typical immature DC (T cell stimulation, IL-12/IL-10 production), but with a slightly altered phenotype of increased CD80 and decreased CD43 expression (markers of maturity).The continuous presence of DEX at a concentration of 10 26 M in the monocyte/DC cultures resulted in the generation of plastic-adherent macrophage-like cells in place of typical immature DC, with increased CD14 expression, but decreased expression of the typical DC markers CD1a, CD40 and CD80. These cells were strongly reactive to acid phosphatase, but equally capable of stimulating T cell proliferation as immature DC. The production of IL-12 by these macrophage-like cells was virtually shut down, whereas the production of IL-10 was significantly higher than that of control immature DC. Conclusion:The continuous presence of a high level of GC during the generation of immature DC from monocytes can modulate this development away from DC towards a macrophage-like cell. The combination of a low CD80 expression and a shutdown of IL-12 production suggests the possibility of DEX-generated cells initiating a Th2-biased response. These effects by DEX on DC development contrast with those by DHEA, which resulted in a more typical DC although possessing a phenotype possibly indicating a more mature state of the cell.

show abstract

Section: Discussionmentioning

confidence: 99%

Opposing effects of dehydroepiandrosterone and dexamethasone on the generation of monocyte-derived dendritic cells

Canning

Grotenhuis

Wit

et al. 2000

European Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…This finding suggests that the high levels of progesterone present during the luteal phase may be involved in regulating STS activity. STS activity in PBLs obtained from men is lower than that in cells from female subjects (26,180). Because many breast tumors are infiltrated by macrophages and lymphocytes (181), it is possible that the STS activity of these cells may make an important contribution to estrogen synthesis within tumors.…”

Section: G Sts Activity In Leukocytes and Thrombocytesmentioning

confidence: 99%

Steroid Sulfatase: Molecular Biology, Regulation, and Inhibition

et al. 2005

View full text Add to dashboard Cite

Steroid sulfatase (STS) is responsible for the hydrolysis of aryl and alkyl steroid sulfates and therefore has a pivotal role in regulating the formation of biologically active steroids. The enzyme is widely distributed throughout the body, and its action is implicated in physiological processes and pathological conditions. The crystal structure of the enzyme has been resolved, but relatively little is known about what regulates its expression or activity. Research into the control and inhibition of this enzyme has been stimulated by its important role in supporting the growth of hormone-dependent tumors of the breast and prostate. STS is responsible for the hydrolysis of estrone sulfate and dehydroepiandrosterone sulfate to estrone and dehydroepiandrosterone, respectively, both of which can be converted to steroids with estrogenic properties (i.e., estradiol and androstenediol) that can stimulate tumor growth. STS expression is increased in breast tumors and has prognostic significance. The role of STS in supporting tumor growth prompted the development of potent STS inhibitors. Several steroidal and nonsteroidal STS inhibitors are now available, with the irreversible type of inhibitor having a phenol sulfamate ester as its active pharmacophore. One such inhibitor, 667 COUMATE, has now entered a phase I trial in postmenopausal women with breast cancer. The skin is also an important site of STS activity, and deficiency of this enzyme is associated with X-linked ichthyosis. STS may also be involved in regulating part of the immune response and some aspects of cognitive function. The development of potent STS inhibitors will allow investigation of the role of this enzyme in physiological and pathological processes.

show abstract

“…In 1978, Shapiro et al (2,3) demonstrated the steroid sulfatase (STS) deficiency in X-linked ichthyosis (XLI). Since then, several clinical features have been proposed to distinguish among the types, especially between XLI and ichthyosis vulgaris (IV), as both types appear at a high frequency (4)(5)(6). IV shows fine, white and irregular scales; the extremities are usually more involved than the trunk.…”

Section: Introductionmentioning

confidence: 99%

Accuracy of the Clinical Diagnosis of Recessive X‐Linked Ichthyosis vs Ichthyosis Vulgaris

Cuevas-Covarrubias

Kofman‐Alfaro

Palencia

et al. 1996

The Journal of Dermatology

View full text Add to dashboard Cite

The present study analyzes the accuracy of the clinical diagnosis of X-linked ichthyosis (XLI) vs ichthyosis vulgaris (IV), in a sample of Mexican patients. The study was double blind, using steroid sulfatase (STS) activity as the golden standard. Twenty male patients were included; 16 corresponded to XLI and 4 to IV. The clinical diagnosis was correct in 9 of the 16 XLI cases (56%) and in 2 of the 4 IV cases (50%). Some clinical findings in XLI, such as cryptorchidism in patients and delayed labor in their mothers, were important features for diagnosis. Statistical analysis of the results showed: among physicians (n = 2) Kappa value 0.50, specific concordance 0.40, and absolute concordance 0.75; other values were sensibility 0.56, specificity 0.50, positive predictive value 0.82, negative predictive value 0.22, accuracy 0.55, prevalence 0.80. In conclusion, the differential diagnosis of XLI and IV is very difficult, and we consider that this is not explained either by personal skills or by other conditions. It could be attributed to the similarities in skin manifestations of these two diseases. The performance of the STS assay is imperative in order to correctly diagnose the disease and offer adequate genetic counseling.

show abstract

Steroid Sulfatase Activities in Human Leukocytes: Biochemical and Clinical Aspects.

Cited by 14 publications

References 14 publications

Opposing effects of dehydroepiandrosterone and dexamethasone on the generation of monocyte-derived dendritic cells

Opposing effects of dehydroepiandrosterone and dexamethasone on the generation of monocyte-derived dendritic cells

Steroid Sulfatase: Molecular Biology, Regulation, and Inhibition

Accuracy of the Clinical Diagnosis of Recessive X‐Linked Ichthyosis vs Ichthyosis Vulgaris

Contact Info

Product

Resources

About