Plasma estrone-sulfate assessment of reduced estrogen production during treatment of metastatic breast carcinoma

Samojlik, E.; Santen, Richard J.; Worgul, T. J.

doi:10.1016/0039-128x(82)90050-2

Cited by 73 publications

(20 citation statements)

References 19 publications

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“…The Superscript Preamplification system RT kit (Life Technologies, Inc.) was used in the synthesis of complementary DNA. cDNA was synthesized from total RNA (2 g) using 25 ng/L of Oligo (dT) [12][13][14][15][16][17][18] Primer (Life Technologies, Inc., Gaithersburg, ND) on a PTC-200 Peltier Thermal Cycler DNA Engine (MJ Research, Inc., Watertown, MA). To test for the presence of genomic DNA contamination, we performed the RT step in the absence of Superscript II RNase H Ϫ Reverse Transcriptase (Life Technologies, Inc.) followed by PCR.…”

Section: Cdna Synthesis and Real-time Polymerase Chain Reaction (Pcr)mentioning

confidence: 99%

“…E1S has a relatively long half-life in the peripheral blood, 13 whereas serum levels of E1S are known to be 10-fold higher than those of unconjugated estrone (E1) or estradiol (E2). 14 Figure 1 represents the pathways of in situ estrogen production in human normal peripheral tissues and/or breast carcinomas. 15,16 E1 is sulfated into E1S by the cytosolic enzyme, estrogen sulfotransferase (EST).…”

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confidence: 99%

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Steroid Sulfatase and Estrogen Sulfotransferase in the Atherosclerotic Human Aorta

Nakamura

Miki

Suzuki

et al. 2003

The American Journal of Pathology

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Various epidemiological studies have demonstrated a relatively low incidence of cardiovascular events in premenopausal women and its marked increment after menopause. In addition, estrogens have been postulated to exert direct anti-atherogenic effects via binding to estrogen receptors in vascular smooth muscle cells (VSMCs). However, not all postmenopausal women develop atherosclerosis despite decreased levels of serum estrogen. Therefore, we believe it is important to examine the status of estrogen metabolism in situ in the human cardiovascular system. Estrone sulfate (E1S) is a major circulating plasma estrogen that is converted into the biologically active estrogen, estrone (E1) by steroid sulfatase (STS). E1 is also sulfated and reverted into E1S by estrogen sulfotransferase (EST). These two enzymes have recently been shown to play important roles in the in situ estrogen actions of estrogen-dependent human tissues and various sex steroid-dependent tumors. STS and EST, however, have not been studied in detail in the human vascular system associated with atherosclerotic changes. In the present study, we evaluated the relative abundance of STS-and ESTimmunoreactive protein and mRNA expression in human aorta using immunohistochemistry and reverse transcription followed by quantitative polymerase chain reaction in addition to enzyme activity. 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. EST expression levels in the VSMCs of these aortas, however, were significantly higher in female aortas with severe atherosclerotic changes and in male aortas than in female aortas with mild atherosclerotic changes. We believe it is important to examine factors regulating the expression and activity of these estrogen-metabolizing enzymes in the human aorta. Various cytokines have been proposed to function as regulators of these enzymes in other tissues. In the present study, we studied the effects of interleukin (IL)-1␤, known to be produced in human atherosclerotic lesions, on the expression of these enzymes using cultured human VSMCs originally obtained from a female patient. IL-1␤ markedly inhibited the expression of STS mRNA and enzyme activity, but stimulated the expression of EST mRNA and enzyme activity. In addition, IL-1␤ also reduced E2 production from E1S and E1 in VSMCs.Results from the present study seem to suggest that the expression levels of both STS and EST mRNA and activity may be significantly associated with the degree of atherosclerotic changes in the female aorta, which may be related to cytokines produced in situ, such as IL-1␤, in human atherosclerotic lesions. Various epidemiological studies have reported a relatively low incidence of cardiovascular events in premenopausal women and its marked increment after menopause.1 Estrogen has, therefore, been proposed as a cardioprotective agent, especially in women.2 In ...

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Section: Cdna Synthesis and Real-time Polymerase Chain Reaction (Pcr)mentioning

confidence: 99%

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confidence: 99%

Steroid Sulfatase and Estrogen Sulfotransferase in the Atherosclerotic Human Aorta

Nakamura

Miki

Suzuki

et al. 2003

The American Journal of Pathology

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“…E1S and E2S have a relatively long half-life in the peripheral blood (10), where serum levels of E1S and E2S are known to be 10-fold higher than those of unconjugated E1 or 17␤-estradiol (11). It was reported recently that in situ estrogen activity in breast cancer, which is estrogen dependent as well as endometrial cancer, may be mainly regulated by the status of intratumoral steroid sulfatase (12,13).…”

Section: Introductionmentioning

confidence: 99%

Steroid Sulfatase and Estrogen Sulfotransferase in Human Endometrial Carcinoma

Utsunomiya¹,

Itō²,

Suzuki

et al. 2004

Clinical Cancer Research

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Purpose: Intratumoral metabolism and synthesis of estrogens are considered to play important roles in the pathogenesis and/or development of human endometrial carcinoma. Steroid sulfatase hydrolyzes biologically inactive estrogen sulfates to active estrogens, whereas estrogen sulfotransferase sulfonates estrogens to estrogen sulfates. However, the status of steroid sulfatase and/or estrogen sulfotransferase in human endometrial carcinoma has not been examined.Experimental Design: We first examined the expression of steroid sulfatase and estrogen sulfotransferase in 6 normal endometrium and 76 endometrial carcinoma using immunohistochemistry to elucidate the possible involvement of steroid sulfatase and estrogen sulfotransferase. We then evaluated the enzymatic activity and the semiquantitative analysis of mRNA using reverse transcription-PCR in 21 endometrial carcinomas. We correlated these findings with various clinicopathological parameters including the expression of aromatase, 17␤-hydroxysteroid dehydrogenase type 1 and type 2.Results: Steroid sulfatase and estrogen sulfotransferase immunoreactivity was detected in 65 of 76 (86%) and 22 of 76 (29%) cases, respectively. Results of immunoreactivity for steroid sulfatase and estrogen sulfotransferase were significantly correlated with those of enzymatic activity and semiquantitative analysis of mRNA. No significant correlations were detected among the expression of the enzymes involved in intratumoral estrogen metabolism. There was a significant correlation between steroid sulfatase/estrogen sulfotransferase ratio and clinical outcomes of the patients. However, there were no significant differences between steroid sulfatase or estrogen sulfotransferase and estrogen receptor, progesterone receptor, Ki67, histologic grade, or clinical outcomes of the patients.Conclusions: Results of our study demonstrated that increased steroid sulfatase and decreased estrogen sulfotransferase expression in human endometrial carcinomas may result in increased availability of biologically active estrogens and may be related to estrogen-dependent biological features of carcinoma.

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“…Quantitatively, ES is the most important blood estrogen. 6,7 Exogenously administered ES has been shown to stimulate mammary tumor growth. 8 To determine whether the cows' milk on the market has any biologically significant hormonal effects, 2 series of uterotrophic assays were performed, 1 with ovariectomized young rats and the other with sexually immature female rats.…”

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Commercial cows' milk has uterotrophic activity on the uteri of young ovariectomized rats and immature rats

Ganmaa

Tezuka

Enkhmaa

et al. 2005

Intl Journal of Cancer

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Cows' milk contains considerable quantities of estrogens, mainly in the form of estrone sulfate (ES). To determine whether the commercial milk has any biologically significant hormonal effects, 2 series of uterotrophic tests were performed, 1 with young ovariectomized rats and the other with sexually immature rats. Thirty-six rats were used for each test. They were divided into 3 groups of 12 animals each, and were kept for 7 days on powdered chow with 1 of 3 drinking solutions: low-fat milk (LFM), artificial milk (AM, negative control), or AM containing ES at 100 ng/ml (positive control). At autopsy, both the wet and blotted uterine weights were measured. The cell heights of uterine epithelia in ovariectomized rats were also determined. The significance of differences among groups was tested by Dunnett's multiple comparisons test. In each test, the weights of the uteri in the LFM group were significantly greater than those of the respective weights in the AM group (p < 0.01). Furthermore, in ovariectomized rats, the uterine epithelialcell height in the LFM group was significantly greater than that observed in the AM group (p < 0.01). The uterotrophic effect of 100 ng/ml ES solution was greater than that of LFM in immature rats (p < 0.01), whereas the effect of the solution was almost comparable to that of LFM in young ovariectomized rats (p > 0.05). In conclusion, commercially available milk has uterotrophic effects in both young ovariectomized rats and sexually immature rats. ' 2005 Wiley-Liss, Inc.Key words: cows'milk; positive uterotrophic test; ovariectomized rats; immature rats Cows' milk contains considerable amounts of estrogens (estrone, estradiol-17b and estriol).1 Because of modern breeding practices, 75% of commercial milk comes from cows during pregnancy, when the estrogen levels in their blood, and hence in their milk, are elevated.2 The hormone levels in milk exceed those in blood, probably owing to hormone synthesis in the mammary glands. The major estrogen in milk is estrone sulfate (ES), 4 which when consumed can be readily converted into estrone or estradiol-17b. 5Because of its hydrophilic nature, this main conjugate can be easily absorbed from the gastrointestinal tract. Quantitatively, ES is the most important blood estrogen.6,7 Exogenously administered ES has been shown to stimulate mammary tumor growth. To determine whether the cows' milk on the market has any biologically significant hormonal effects, 2 series of uterotrophic assays were performed, 1 with ovariectomized young rats and the other with sexually immature female rats. Material and methodsThe low-fat (1%) milk used in this study (Holstein milk sterilized at 130°C for 2 sec) was the same one as that was used previously. The artificial milk (AM), which was used as a negative control solution, contained the same amount of protein (gluten fortified with lysine, DL-methionine, threonine and valine), fat (coconut oil) and carbohydrate (dextrin maltose) as the low-fat milk. The composition of the AM has been described elsewhere. 9 A ...

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Plasma estrone-sulfate assessment of reduced estrogen production during treatment of metastatic breast carcinoma

Cited by 73 publications

References 19 publications

Steroid Sulfatase and Estrogen Sulfotransferase in the Atherosclerotic Human Aorta

Steroid Sulfatase and Estrogen Sulfotransferase in the Atherosclerotic Human Aorta

Steroid Sulfatase and Estrogen Sulfotransferase in Human Endometrial Carcinoma

Commercial cows' milk has uterotrophic activity on the uteri of young ovariectomized rats and immature rats

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