Conjugation of Urinary Phenolic Steroids in the Nonpregnant Human Female with Particular Reference to Estrone Sulfate<sup>1</sup>

Hobkirk, R.; Nilsen, Mona; Blahey, P. R.

doi:10.1210/jcem-29-3-328

Cited by 49 publications

(17 citation statements)

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“…Therefore, the proximal tubular cells in kidney can excrete E1S metabolized from E1S by EST. Moreover, E1S in human adult urine is known to be high (8). In the fetal kidney, the expression of EST immunoreactive protein was present in interstitial and stromal cells surrounding the urinary tubules, but not in the tubules or glomeruli.…”

Section: Discussionmentioning

confidence: 95%

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Systemic Distribution of Steroid Sulfatase and Estrogen Sulfotransferase in Human Adult and Fetal Tissues

Miki

Nakata

Suzuki

et al. 2002

The Journal of Clinical Endocrinology &Amp; Metabolism

154

125

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Estrogens play a key role in various target tissues. Enzymes involved in the biosynthesis and metabolism of these sex steroids also regulate estrogenic actions in these tissues. 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 various sex steroid-dependent human tumors. However, the distribution of STS and EST in normal adult and fetal human tissues remains largely unknown. Therefore, in this study, in addition to examining the tissue distribution of both STS and EST mRNA in human adult and fetal tissues using RT followed by quantitative PCR, we studied the activity of these enzymes using 3 H-labeled E1/E1S as substrates in the homogenates of various human adult tissues. We also examined the localization of STS and EST protein in human adult and fetal tissues using immunohistochemistry, and that of EST mRNA in the adult kidney using laser dissection microscopy and PCR. STS mRNA, enzyme activity, and immunoreactivity were either absent or detected at very low levels in all adult and fetal tissues examined in this study. EST mRNA expression, however, was detected in all of the tissues examined, except for adult spleen and pancreas. EST enzyme activities were consistent with those of mRNA expression in the great majority of the tissues examined. Marked EST immunoreactivity was detected in hepatocytes, adrenal gland (adult, zona fasciculate to the reticularis; fetus, fetal zone), and epithelial cells of the gastrointestinal tract, smooth muscle cells of the tunica media in aorta, Leydig cells of the testis, and syncytiotrophoblast of the placenta. Patterns of EST immunolocalization were similar between adult and fetal human tissues, but EST immunoreactivity was detected in the urinary tubules of adult kidney, whereas in the fetal kidney, it was localized in the interstitial cells surrounding the urinary tubules. In the adult kidney, the presence of EST mRNA was also confirmed in the cells of urinary tubules using laser dissection microscopy and RT-PCR.Although the number of human tissues available for examination in this study was limited, our results suggest that between the enzymes involved in estrogen activation or inactivation, EST and not STS is the more widely expressed enzyme in various peripheral tissues in humans. We speculate that EST may play an important role in protecting peripheral tissues from possible excessive estrogenic effects. (J Clin Endocrinol Metab 87: 5760 -5768, 2002)

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Section: Discussionmentioning

confidence: 95%

“…7). In addition, E1S has been shown to be a predominant form of estrogen in the urine and milk (8,9). E1S is transformed into a biologically active form, E1, by steroid (estrone) sulfatase (STS; Refs.…”

mentioning

confidence: 99%

Systemic Distribution of Steroid Sulfatase and Estrogen Sulfotransferase in Human Adult and Fetal Tissues

Miki

Nakata

Suzuki

et al. 2002

The Journal of Clinical Endocrinology &Amp; Metabolism

154

125

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“…10-ml blood samples were taken at i, 1, 2, 4, 6, and 8 hr and 20-35-ml blood samples were taken at 11,14,19, and 24 hr. Blood was heparinized, centrifuged immediately, and the plasma frozen at -15°C until extracted.…”

Section: Methodsmentioning

confidence: 99%

“…estradiol-6,7-3H infusions are shown in Table V (13,14). E1S has been the major urinary estrogenic metabolite.…”

Section: Conversion Of Es To Es the Data Obtained Frommentioning

confidence: 99%

Estrone Sulfate: Production Rate and Metabolism in Man

Ruder¹,

Loriaux²,

Lipsett³

1972

J. Clin. Invest.

246

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A B S T R A C T Since estrone sulfate (E1S) is present at high concentration in plasma, we have examined the parameters of the plasma estrone, estradiol, E1S system. The metabolic clearance rate of EiS was 157 liter/day (range 70-292) in men and women. Estimated plasma production rates of E1S were (/Agrams per day): men, 77; women, early follicular phase, 95; women, early luteal phase, 182. The conversion of plasma estrone and estradiol to EiS was measured and from these data and the metabolic clearance rates of the estrogens, the transfer factors were p51'18 = 0.54 and p'2'1' = 0.65. Using average production rates, all plasma E1S could be shown to be derived from plasma estrone and estradiol.The conversion of plasma E1S to plasma estrone and estradiol was studied. The calculated transfer factors were: p'1`81 = 0.21, pBis2 = 0.014. Essentially, similar data were obtained when E1S was given by mouth to two subjects.We conclude: (a) EiS is a major circulating plasma estrogen and has a long plasma half-life; (b) the large contributions of estrone and estradiol to plasma E1S are more than sufficient to account for all the circulating plasma E1S.

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“…The ester has also been noted in the urines of males and non-pregnant females after the administration of labelled oestrogen precursors (Hobkirk, Nilsen & Purre, 1966;Hobkirk, Nilsen & Blakey, 1969) whereas its presence in human plasma (Purdy, Engel & Oncley, 1961) and (in high concentration) in stallion testes (Raeside, 1969) has also been demonstrated.…”

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confidence: 95%

Metabolism of sodium oestrone [35S] sulphate in the rat

Dolly¹,

Curtis²,

Dodgson³

et al. 1970

Biochemical Journal

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Conjugation of Urinary Phenolic Steroids in the Nonpregnant Human Female with Particular Reference to Estrone Sulfate¹

Cited by 49 publications

References 0 publications

Systemic Distribution of Steroid Sulfatase and Estrogen Sulfotransferase in Human Adult and Fetal Tissues

Systemic Distribution of Steroid Sulfatase and Estrogen Sulfotransferase in Human Adult and Fetal Tissues

Estrone Sulfate: Production Rate and Metabolism in Man

Metabolism of sodium oestrone [35S] sulphate in the rat

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Conjugation of Urinary Phenolic Steroids in the Nonpregnant Human Female with Particular Reference to Estrone Sulfate1

Cited by 49 publications

References 0 publications

Systemic Distribution of Steroid Sulfatase and Estrogen Sulfotransferase in Human Adult and Fetal Tissues

Systemic Distribution of Steroid Sulfatase and Estrogen Sulfotransferase in Human Adult and Fetal Tissues

Estrone Sulfate: Production Rate and Metabolism in Man

Metabolism of sodium oestrone [35S] sulphate in the rat

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Conjugation of Urinary Phenolic Steroids in the Nonpregnant Human Female with Particular Reference to Estrone Sulfate¹