Search

Testicular steroids can alter the activity and expression of enzymes within the liver and may influence the metabolism of skatole and androstenone, which are responsible for boar taint. Plasma levels of estrone sulfate (E1S) are indicative of the steroidogenic capacity of the boar and are variable between animals of similar live weights at slaughter. This study aimed to characterize the relationship between steroidogenic capacity and the metabolism of boar taint compounds by relating plasma E1S levels at slaughter weight to the expression levels of genes regulating the metabolism of androstenone and skatole, along with their respective metabolite profiles. RT-qPCR was used to evaluate gene expression in the liver. Hepatocytes were also isolated and treated with androstenone or skatole, with metabolite levels in the incubation media quantified by high-performance liquid chromatography. Plasma E1S levels ranged from 2.2–108.5 ng/mL and were positively correlated with overall skatole metabolism (p = 0.038), the production of metabolites 3-methyloxindole (p = 0.026) and 3-hydroxy-3-methyloxindole (p = 0.036), and expression levels of key genes involved in skatole metabolism, specifically CYP2C33 (p = 0.0042), CYP2C49 (p = 0.022), and CYB5R1 (p = 0.017). There was no association between androstenone metabolism and plasma E1S concentrations; however, there was evidence of possible co-regulation amongst genes involved in the metabolism of androstenone, skatole, and estrogens. These findings indicate that steroidogenic capacity is related to the rate of skatole, but not androstenone metabolism, in slaughter-weight boars. [ABSTRACT FROM AUTHOR]

Surgical castration is a significant welfare concern within the swine industry; however, it is currently the most effective method to prevent boar taint, which is a meat quality issue that develops in entire male pigs due to the accumulation of androstenone and skatole in the fat. Metabolism of the boar taint compounds occurs within the liver and promotes their excretion, ultimately reducing the extent of their accumulation in the fat. Previous research has demonstrated that plasma concentrations of estrone sulfate (E1S), which are indicative of steroid hormone status in the boar, are highly variable between individual animals of similar live body weights at slaughter. Testicular steroids are known to influence the activity and expression of some enzymes regulating the metabolism of skatole, but the effect of hormone concentrations on the entire expression profile of enzymes responsible for boar taint metabolism has not been characterized. Therefore, the objective of this study was to relate plasma E1S concentrations at slaughter to expression levels of genes regulating the metabolism of androstenone and skatole and their respective metabolite profiles in isolated hepatocytes, to further characterize the relationship between hormone status and boar taint metabolism. Blood and liver samples were collected from 5-mo-old crossbred [(Yorkshire x Landrace) x Duroc] boars (n = 8)] at slaughter. Plasma E1S concentrations were quantified using a radioimmunoassay and gene expression in the liver was evaluated by RT-qPCR. Hepatocytes were also isolated and incubated with androstenone or skatole, with metabolite concentrations in the incubation media quantified by high-performance liquid chromatography. Statistical analysis was performed using Pearson correlation. Plasma E1S concentrations at slaughter ranged from 2.2-108.5 ng/mL and were positively correlated with overall skatole metabolism (r = 0.77, P = 0.0265), the production of the Phase I skatole metabolites 3-methyloxindole (3MOI; r = 0.80, P = 0.0183), and 3-hydroxy-3-methyloxindole (HMOI; r = 0.73, P = 0.0413), as well as expression levels of CYP2C33 (r = 0.88, P = 0.0042), CYP2C49 (r = 0.78, P = 0.0221), and CYB5R1 (r = 0.80, P = 0.0165), which regulate skatole metabolism. A strong positive relationship was also identified between overall skatole metabolism and the production of 3MOI (r = 0.96, P = 0.0001) and HMOI (r = 0.93, P = 0.001). Androstenone metabolism primarily resulted in the production of Phase II glucuronide metabolites, but the levels produced were not related to E1S concentrations or gene expression levels. Taken together, these results demonstrate that plasma E1S concentrations are related to the rate of skatole, but not androstenone, metabolism in mature boars. Additional research is required to assess the potential of E1S concentrations as a biomarker for the rate of skatole metabolism in vivo and establish thresholds that could be used to identify boars with high and low rates of metabolism. This may provide an opportunity to develop targeted treatments for boar taint based on the metabolic status of the animal. [ABSTRACT FROM AUTHOR]

Quantitation of endogenous steroids and their precursors is essential for diagnosis of a wide range of endocrine disorders. Usually, these analyses have been carried out using immunoassays. However, immunoassays often overestimate concentrations due to assay interference by other endogenous steroids, especially for low concentrations. Mass spectrometry based methods offer superior specificity, accuracy, and sensitivity. We therefore present a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with automated sample preparation for determination of 17α-hydroxyprogesterone (17OHP), cortisol, cortisone, dehydroepiandrosterone sulfate (DHEAS), androstenedione (A4), testosterone (T), and estrone sulfate (E1S). Samples were prepared using protein precipitation and 96-well filter plates, fully automated in a pipetting robot and analyzed by LC-MS/MS. Serum samples from 187 healthy children and adolescents aged 5-18 years were used to study hormone changes in relation to sex and pubertal stage. Lower limit of quantification for 17OHP was 0.7 nmol/L, for cortisol 11 nmol/L, for cortisone 2 nmol/L, for DHEAS 0.1 µmol/L, and for A4, T, and E1S, 0.2 nmol/L. This study showed a general increase in 17OHP, DHEAS, A4, T and E1S in both genders during puberty. In boys, A4 and T increased significantly throughout pubertal development. Girls had significantly higher A4 and E1S concentrations, while boys had higher T concentrations. No sex- or puberty-specific differences were seen in cortisol or cortisone concentrations. To the best of our knowledge, this is the first presentation of changes in serum E1S concentrations during pubertal development in healthy children. [ABSTRACT FROM AUTHOR]

Estrone sulfate (E1S) is the most abundant circulating estrogen and it has the potential to be used as a biomarker in certain conditions where estimation of low levels of estrogen or changes in relative levels of estrogens are important. This review will critically consider the role of estimating E1S for clinical laboratory practice. As E1S is an estrogen, a wider discussion of estrogens is included to contextualize the review. Assays have been available for a number of years for these estrogens and they have been measured in a number of clinical research studies. However, E1S remains a rarely ordered test. This review highlights the literature that suggests the possible advantages of measuring E1S in addition to, or possibly in place of, the more commonly measured estradiol (E2) and the less commonly measured estrone (E1). The potential biomarker role of E1S in risk stratification for breast cancer, in promotion of proliferation of endometrial cancer, in prognostic information in advanced prostatic carcinoma, and in the monitoring of response to certain hormonal therapy for malignancy is discussed. The methods available for the measurement of E1S are reviewed and the limitations of the current methodologies are described. In conclusion, E1S has some interesting potential applications in clinical laboratory medicine that require further investigation. [ABSTRACT FROM AUTHOR]

Purpose: Inter-individual differences in estrogen concentrations during treatment with aromatase inhibitors (AIs) may contribute to therapeutic response and toxicity. The aim of this study was to determine plasma concentrations of estradiol (E2), estrone (E1), and estrone sulfate (E1S) in a large cohort of AI-treated breast cancer patients. Methods: In a randomized, multicenter trial of postmenopausal women with early-stage breast cancer starting treatment with letrozole ( n = 241) or exemestane ( n = 228), plasma estrogen concentrations at baseline and after 3 months were quantitated using a sensitive mass spectrometry-based assay. Concentrations and suppression below the lower limit of quantification (LLOQ) were compared between estrogens and between drugs. Results: The ranges of baseline estrogen concentrations were

Gynecological diseases such as endometriosis, adenomyosis and uterine fibroids, and gynecological cancers including endometrial cancer and ovarian cancer, affect a large proportion of women. These diseases are estrogen dependent, and their progression often depends on local estrogen formation. In peripheral tissues, estrogens can be formed from the inactive precursors dehydroepiandrosterone sulfate and estrone sulfate. Sulfatase and sulfotransferases have pivotal roles in these processes, where sulfatase hydrolyzes estrone sulfate to estrone, and dehydroepiandrosterone sulfate to dehydroepiandrosterone, and sulfotransferases catalyze the reverse reactions. Further activation of estrone to the most potent estrogen, estradiol, is catalyzed by 17-ketosteroid reductases, while estradiol can also be formed from dehydroepiandrosterone by the sequential actions of 3b-hydroxysteroid dehydrogenase-Δ4-isomerase, aromatase, and 17-ketosteroid reductase. This review introduces the sulfatase and sulfotransferase enzymes, in terms of their structures and reaction mechanisms, and the regulation and different transcripts of their genes, together with the importance of their currently known single nucleotide polymorphisms. Data on expression of sulfatase and sulfotransferases in gynecological diseases are also reviewed. There are often unchanged mRNA and protein levels in diseased tissue, with higher sulfatase activities in cancerous endometrium, ovarian cancer cell lines, and adenomyosis. This can be indicative of a disturbed balance between the sulfatase and sulfotransferases enzymes, defining the potential for sulfatase as a drug target for treatment of gynecological diseases. Finally, clinical trials with sulfatase inhibitors are discussed, where two inhibitors have already concluded phase II trials, although so far with no convincing clinical outcomes for patients with endometrial cancer and endometriosis. [ABSTRACT FROM AUTHOR]

The development of boar taint is dependent on the balance between the rate of androstenone synthesis and metabolism, which regulates the quantity of androstenone available for accumulation in the fat. The pubertal production of androstenone and other sex steroids is influenced by sexual maturity status and preceded by a significant period of hormone production during postnatal development that occurs from 14 to 35 days of age (DOA). However, the relationship between postnatal and pubertal hormone production is not well understood. Therefore, the purpose of this study was to determine if postnatal hormone concentrations can be used to predict sexual maturity status and boar taint development at puberty. Crossbred [(Yorkshire x Landrace) x Duroc] boars (n=90)] were housed in groups of 10. Blood samples were taken at 14, 21, 28, and 35 DOA and again at 120, 130, and 140kg live weights (LWs) along with backfat samples. Plasma and fat androstenone concentrations were quantified using an androstenone-specific ELISA. Plasma estrone sulfate (E1S) concentrations were determined by RIA and used as an indicator of sexual maturity status. Statistical analysis was performed using Spearman correlation. Several nonlinear monotonic relationships were identified between postnatal and pubertal hormone concentrations and are presented in Table 1. A moderate positive correlation was identified between plasma androstenone concentrations at 21 and 28 DOA and fat androstenone concentrations at 120, 130, and 140kg LWs, and between E1S concentrations at 21 DOA and E1S concentrations at 120, 130, 140kg LWs. However, the strength of the relationship between postnatal and pubertal hormone concentrations was insufficient for accurately predicting sexual maturity status or boar taint at puberty. These results suggest that additional factors regulating the development of boar taint, such as the rate of metabolism or accumulation, should be considered in future efforts to develop a predictive model using postnatal hormone concentrations. [ABSTRACT FROM AUTHOR]

Among solute carrier proteins, the organic anion transporters (OATs) play an important role for the elimination or reabsorption of endogenous and exogenous negatively charged anionic compounds. Among OATs, SLC22A9 (hOAT7) transports estrone sulfate with high affinity. The net decrease of estrogen, especially in post-menopausal women induces rapid bone loss. The present study was performed to search the SNP within exon regions of SLC22A9 in Korean females with osteoporosis. Fifty healthy controls and 50 osteoporosis patients were screened for the genetic polymorphism in the coding region of SLC22A9 using GC-clamped PCR and denaturing gradient gel electrophoresis (DGGE). Six SNPs were found on the SLC22A9 gene from Korean women with/without osteoporosis. The SNPs were located as follows: two SNPs in the osteoporosis group (A645G and T1277C), three SNPs in the control group (G1449T, C1467T and C1487T) and one SNP in both the osteoporosis and control groups (G767A). The G767A, T1277C and C1487T SNPs result in an amino acid substitution, from synonymous vs nonsynonymous substitution arginine to glutamine (R256Q), phenylalanine to serine (F426S) and proline to leucine (P496L), respectively. The Km values and Vmax of the wild type, R256Q, P496L and F426S were 8.84, 8.87, 9.83 and 12.74 μ M, and 1.97, 1.96, 2.06 and 1.55 pmol/oocyte/h, respectively. The present study demonstrates that the SLC22A9 variant F426S is causing inter-individual variation that is leading to the differences in transport of the steroid sulfate conjugate (estrone sulfate) and, therefore this could be used as a marker for certain disease including osteoporosis. [ABSTRACT FROM AUTHOR]

ABSTRACT Blood estrone sulfate (E1S), estrone (E1), estradiol (E2) and progesterone (P4) in newborn piglets were measured to clarify the relationships among birth and placental weight, vitality of offspring and litter size. First, the association between vital status (normal, weak and stillborn) from 165 newborn piglets of 18 litters and steroid concentrations; second, steroid concentrations from 152 newborn normal piglets and litter size; and third, steroid content in fetal placenta from 50 newborn normal piglets of six litters and litter size, were investigated. In the normal group, the birth and placental weight were significantly higher than those in the other groups. Blood E1S levels in the stillborn group were significantly lower, whereas E1, E2 and P4 were significantly higher compared to the normal group. Blood and placental E1S levels in the small litter group were significantly higher than those in the other groups. However, there was no significant difference among the three litter size groups in the levels of steroid hormones in maternal blood. These results indicate that vitality of newborn piglets is related to E1S concentration of neonate, to birth weight and placental weight. However, steroid hormone concentrations of newborn piglets were greatly affected by the number of littermates. [ABSTRACT FROM AUTHOR]

The aim of this review is to describe the associations between circulating plasma estrogens and prostate cancer (PCa). We recall the origins of estrogens, which derive from the aromatization of androgens, but also by sulfatase hydrolysis of estrone sulfate (E1-S), the main circulating plasma estrogen. We evoke that the carcinogenic effects of estrogens were demonstrated in the rat and murine prostate when estrogens and androgens were simultaneously administered to them. We also describe estrogen proliferative activity and the genotoxicity of estrogen-hydroxylated metabolites with the formation of DNA adducts. We report published aromatase and CYP1B1 polymorphisms found in men with PCa. We published a bibliography on the relation between PCa and prostate inflammation, as well as the possible role of obesity in the aggressiveness of PCa. In this review, we provide an exhaustive list of assays carried out in subjects at high risk for PCa compared with Caucasians, showing that higher estrogen levels were found in the plasma of these subjects at high risk for PCa. Plasma estrone was the estrogen for which plasma concentration was highest in subjects of African descent. We recall the links observed between plasma estrogens, particularly E1-S, and PCa aggressiveness. Finally, we describe assays for determining hydroxylated estrogens and DNA adducts in the urine of men with PCa. We insist on the importance of the technology employed in estrogen measurement and propose the use of mass spectrometry methods to carry out estrogen assays, in order to decrease variability in the results of plasma estrogen assays. [ABSTRACT FROM AUTHOR]

Single nucleotide polymorphisms (SNPs) are the most common form of human genetic variation. Nonsynonymous SNPs (nsSNPs) change an amino acid. Organic anion transporters (OATs) play an important role in eliminating or reabsorbing endogenous and exogenous organic anionic compounds. Among OATs, hOAT4 mediates high affinity transport of estrone sulfate and dehydroepiandrosterone sulfate. The rapid bone loss that occurs in post-menopausal women is mainly due to a net decrease of estrogen. In the present study we searched for SNPs within the exon regions of hOAT4 in Korean women osteoporosis patients. Fifty healthy subjects and 50 subjects with osteoporosis were screened for genetic polymorphism in the coding region of SLC22A11 (hOAT4) using GC-clamp PCR and denaturing gradient gel electrophoresis (DGGE). We found three SNPs in the hOAT4 gene. Two were in the osteoporosis group (C483A and G832A) and one in the normal group (C847T). One of the SNPs, G832A, is an nsSNP that changes the 278th amino acid from glutamic acid to lysine (E278K). Uptake of [3H] estrone sulfate by oocytes injected with the hOAT4 E278K mutant was reduced compared with wild-type hOAT4. Km values for wild type and E278K were 0.7 µM and 1.2 µM, and Vmax values were 1.8 and 0.47 pmol/oocyte/h, respectively. The present study demonstrates that hOAT4 variants can causing inter-individual variation in anionic drug uptake and, therefore, could be used as markers for certain diseases including osteoporosis. [ABSTRACT FROM AUTHOR]

The aim was to evaluate the relationship of prepartum plasma estrone sulfate (E1S) and estradiol-17β (E2β) concentrations with the weight of the calf and the placental parameters. Holstein–Friesian cows ( n = 33) inseminated artificially with Japanese Black beef bull semen at Hiroshima University Farm in Japan were used for the experiment. Blood samples were taken every day from day 270 of gestation until the day after calving. The plasma samples were analyzed for E1S and E2β by enzyme immunoassay. The calf birth weight was taken immediately after calving. Complete fetal membranes were collected from 19 cattle and the weights of the placental components and the number of cotyledons were recorded. All 33 cattle delivered singleton normal calves. The prepartum plasma E1S concentration was found to correlate significantly ( P < 0.01) with the calf birth weight ( r = 0.83), total fetal membrane weight ( r = 0.81), cotyledonary weight ( r = 0.79) and inter-cotyledonary membrane weight ( r = 0.64), but it did not correlate significantly with the number of cotyledons, whereas prepartum plasma E2β was not found to correlate significantly with the weight of either the calf or any of the placental components except the number of cotyledons. In conclusion, prepartum plasma E1S, not plasma E2β, was found to correlate significantly with the weight of the calf and the placental components. [ABSTRACT FROM AUTHOR]

The sulfatase family of enzymes catalyzes hydrolysis of sulfate ester bonds of a wide variety of substrates. Seventeen genes have been identified in this class of sulfatases, many of which are associated with genetic disorders leading to reduction or loss of function of the corresponding enzymes. Amino acid sequence homology suggests that the enzymes have similar overall folds, mechanisms of action, and bivalent metal ion-binding sites. A catalytic cysteine residue, strictly conserved in prokaryotic and eukaryotic sulfatases, is post-translationally modified into a formylglycine. Hydroxylation of the formylglycine residue by a water molecule forming the activated hydroxylformylglycine (a formylglycine hydrate or a gem-diol) is a necessary step for the enzyme’s sulfatase activity. Crystal structures of three human sulfatases, arylsulfatases A and B(ARSA and ARSB), and estrone/dehydroepiandrosterone sulfatase or steroid sulfatase (STS), also known as arylsulfatase C, have been determined. While ARSA and ARSB are water-soluble enzymes, STS has a hydrophobic domain and is an integral membrane protein of the endoplasmic reticulum. In this article, we compare and contrast sulfatase structures and revisit the proposed catalytic mechanism in light of available structural and functional data. Examination of the STS active site reveals substrate-specific interactions previously identified as the estrogen-recognition motif. Because of the proximity of the catalytic cleft of STS to the membrane surface, the lipid bilayer has a critical role in the constitution of the active site, unlike other sulfatases. [ABSTRACT FROM AUTHOR]

Inhibitors of steroid sulfatase are being developed as a novel therapy for hormone-dependent breast cancer in postmenopausal women. Data suggest that steroid sulfatase (STS) activity is much higher than aromatase activity in breast tumors and high levels of STS mRNA expression in tumors are associated with a poor prognosis. STS hydrolyzes steroid sulfates, such as estrone sulfate and dehydroepiandrosterone sulfate (DHEAS), to estrone and DHEA, which can be converted to steroids with potent estrogenic properties, that is, estradiol and androstenediol, respectively. Several potent irreversible STS inhibitors have now been identified, including STX64 (BN83495), a tricyclic sulfamate ester. This drug recently completed the first-ever trial of this new type of therapy in postmenopausal women with estrogen receptor-positive metastatic breast cancer. STX64, tested at 5-mg and 20-mg doses, was able to almost completely block STS activity in peripheral blood lymphocytes and tumor tissues. Inhibition of STS activity was associated with significant reductions in serum concentrations of androstenediol and estrogens. Unexpectedly, serum androstenedione concentrations also decreased by up to 86%, showing that this steroid, which is the main substrate for the aromatase in postmenopausal women, is derived mainly from the peripheral conversion of DHEAS. Of eight patients who completed therapy, five showed evidence of stable disease for up to 7.0 months. This new endocrine therapy offers considerable potential for the treatment of hormone-dependent breast cancer in postmenopausal women. [ABSTRACT FROM AUTHOR]

Although the sulfate/anion transporter (sat-I; SLC26A1) was isolated from a rat liver cDNA library by expression cloning, localization of sat-I within the liver and its contribution to the transport of sulfate and organo sulfates have remained unresolved. In situ hybridization and immunohistochemical studies were undertaken to demonstrate the localization of sat-I in liver tissue. RT-PCR studies on isolated hepatocytes and liver endothelial and stellate cells in culture were performed to test for the presence of sat-I in these cells. In sulfate uptake and efflux experiments, the substrate specificity of sat-I was evaluated. Sat-I mRNA was found in hepatocytes and endothelial cells. Sat-I protein was localized in sinusoidal membranes and along the borders of hepatocytes. The canalicular region and bile capillaries were not stained. Sulfate uptake was only slightly affected by sulfa- moyl diuretics or organo sulfates. Sulfate efflux from sat-I-expressing oocytes was enhanced in the presence of bicarbonate, indicating sulfate/bicarbonate exchange. Estrone sulfate was not transported by sat-I. Sat-I may be responsible for the uptake of inorganic sulfate from the blood into hepatocytes to enable sulfation reactions. In hepatocytes and endothelial cells, sat-I may also supply sulfate for proteoglycan synthesis. [ABSTRACT FROM AUTHOR]

The human organic anion transporter, OAT3 (SLC22A8), plays a critical role in renal drug elimination, by mediating the entry of a wide variety of organic anions, including a number of commonly used pharmaceuticals, into the renal proximal tubular cells. To understand the nature and extent of genetic variation in OAT3, and to determine whether such variation affects its function, we identified OAT3 variants in a large, ethnically diverse sample population and studied their transport activities in cellular assays. We identified a total of 10 distinct coding-region variants, which altered the encoded amino acid sequence, in DNA samples from 270 individuals (80 African-Americans, 80 European-Americans, 60 Asian-Americans, and 50 Mexican- Americans). The overall prevalence of these OAT3 variants was relatively low among the screened population, with only three variants having allele frequencies of > 1% in a particular ethnic group. Clones of each variant were created by site-directed mutagenesis, expressed in HEK-293 cells, and tested for function using the model substrates, estrone sulfate (ES) and cimetidine (CIM). The results revealed a high degree of functional heterogeneity among OAT3 variants, with three variants (p. Arg149Ser, p. Gln239Stop, and p. Ile260Arg) that resulted in complete loss of function, and several others with significantly reduced function. One of the more common variants (p. Ile305Phe), found in 3.5% of Asian-Americans, appeared to have altered substrate specificity. This variant exhibited a reduced ability to transport ES, but a preserved ability to transport CIM. These data suggest that genetic variation in OAT3 may contribute to variation in the disposition of drugs. [ABSTRACT FROM AUTHOR]

The rat organic anion transporter 3 (rOAT3) has recently been identified as the third isoform of the OAT family. The mechanisms that regulate rOAT3's functions remain to be elucidated. rOAT3 contributes for moving a number of negatively charged organic compounds between cells and their extracellular milieu. Caveolin (Cav) also plays a role as a membrane transporter. To address the relationship of these two proteins, we investigated the protein-protein interaction between rOAT3 and Cav-1. The rOAT3 mRNA and protein expression were observed in the rat kidney, and the expressions of Cav-1 mRNA and protein were also detected in the kidney. Confocal microscopy of the immuno-cytochemistry experiments using primary cultured renal proximal tubular cells showed that rOAT3 and Cav-1 were co-localized at the plasma membrane. This finding was confirmed by Western blot analysis using isolated caveolae-enriched membrane fractions from the rat kidney and immuno-precipitation experimentation. When rOAT3's synthesized cRNA of rOAT3 along with the antisense oligo deoxynucleotide ofXenopusCav-1 were co-injected intoXenopusoocytes, the [ 3 H] estrone sulfate uptake was significantly decreased. These findings suggest that rOAT3 and caveolin-1 share a cellular expression in the plasma membrane and Cav-1 up-regulates the organic anionic compound uptake via rOAT3 under normal physiological conditions. IUBMB Life, 57: 109–117, 2005 [ABSTRACT FROM AUTHOR]

The article offers information on the treatment of lactating and nonlactating parous cows with 12 mg of follicle-stimulating hormone (FSH-P) to evaluate development of multiple bovine fetuses. It mentions the ovulation rate is the first limiting factor to increasing cow productivity for beef cattle; and also mentions some bovine females had the capacity to gestate up to three fetuses per uterine horn.

The effect of diet on serum estrogen levels was investigated in 17 healthy premenopausal women consuming defined diets prepared in a metabolic unit. During an initial 4-wk control period all women consumed a typical Western diet (40% of total calories from fat, 400 mg cholesterol/d, 12 g dietary fiber/d, and a ratio of polyunsaturated to saturated fatty acids [P:S] of 0.5). After this control period they were switched to a low-fat, high-fiber diet for 8-10 wk, which consisted of 25% of calories from fat, P:S of 1.0, cholesterol of 200 mg cholesterol/ d, and 40 g dietary fiber/d. Compared with the control period 16 of 17 women had lower serum estrone sulfate levels on the low-fat, high-fiber diet. There was an average decrease of 36% with mean levels decreasing from 2. 1 1 ± 0.25 nmol/L (x ± SEM) on the control diet to 1.29 ± 0. 19 nmol/L on the experimental diet (p < 0.001). We conclude that a low-fat, high-fiber diet can significantly reduce serum estrone sulfate levels. [ABSTRACT FROM AUTHOR]