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PubMed1998

Phyto-oestrogen excretion and rate of bone loss in postmenopausal women.

OBJECTIVE: The hypothesis was tested that the rate of postmenopausal bone loss is inversely associated with long-term urinary excretion of phyto-oestrogens, as a marker of habitual dietary intake. DESIGN: Secondary analysis of a 10-year follow-up study (1979 1989) among postmenopausal women in the Netherlands. SUBJECTS: From the original population of 154 women, 32 women were selected with an annual rate of radial bone loss of < or = 0.5% over the first 5 years of the study and 35 women with a rate of > or = 2.5% per year. METHODS: The isoflavonoids genistein, daidzein and equol, and the lignan enterolactone were determined by gas chromatography mass spectrometry in aggregate samples from annually collected urine samples. Cortical bone density of the radius had previously been measured annually by single-photon absorptiometry. RESULTS: Excretion of isoflavonoids did not differ between both groups, although in multivariate analysis equol excretion was weakly positively associated with rate of bone loss in the 5 years after the menopause. Enterolactone excretion was significantly higher in the group with high rate of bone loss. This positive association remained in multivariate linear regression analysis after adjustment for age, years since menopause, body mass index and intake of calcium, vegetable protein and dietary fibre. CONCLUSIONS: Enterolactone excretion is likely to be an indicator of consumption of grains and legumes; it is not clear whether the observed positive association with rate of bone loss is a causal one. Our results do not support a preventive effect of low, unsupplemented dietary intake of phyto-oestrogens on postmenopausal cortical bone loss. However, no conclusions can be drawn about effects of higher doses of phyto-oestrogens.

4-Butyrolactone↗
PubMed2006

Soya isoflavones suppress phorbol 12-myristate 13-acetate-induced COX-2 expression in MCF-7 cells.

Epidemiological studies indicate that Asian women have a lower incidence of breast cancer compared with their counterparts in the West, and soya consumption has been suggested as a contributory factor. Clinical and animal studies have revealed that cyclooxygenase-2 (COX-2) expression is associated with a risk of breast cancer. In the present study, we investigated the effect of soya isoflavones on the expression of COX-2 in the breast cell line MCF-7. Genistein, daidzein and equol were found to inhibit COX-2 expression induced by phorbol 12-myristate 13-acetate (PMA). Similar findings were observed in the COX-2 protein analysis. In order to study transcriptional control, a fragment of the 5'-flanking region of the hCOX-2 gene was amplified and inserted into a firefly luciferase reporter plasmid. The reporter assay indicated that the transactivation of the hCOX-2 promoter was induced by PMA, and activity was inhibited with the co-administration of genistein, daidzein or equol. An activator protein-1 (AP-1)/cyclic AMP response element binding protein (CREB) binding site (-59/-53) was identified in hCOX-2 promoter, and this could be critical in PMA-induced COX-2 expression. Truncation reporter plasmids with (-70/-36) and without (-51/-36) AP-1/CREB were constructed for subsequent analysis. The results revealed that the hCOX-2 promoter transactivation suppressed by isoflavone could be dependent on AP-1/CREB binding. Nonetheless, this study illustrated that the soya isoflavones reduced COX-2 expression, which could be important in the post-initiation events of breast carcinogenesis.

Anticarcinogenic Agents↗
PubMed2006

Effects of phytoestrogens on testosterone secretion by Leydig cells from Biłgoraj ganders (Anser anser).

The aim of this study was to examine ganders at different stages of the reproductive season and the effect of: (1) diets with high phytoestrogen content and (2) in vitro phytoestrogen treatment on testosterone secretion by isolated Leydig cells. Thirty-six male Biłgoraj geese were fed control diets with low phytoestrogen content (containing grass meal) and diets with high phytoestrogens (containing alfalfa meal and soy). Testes were obtained from both groups of ganders at three different times of the breeding season: peak of reproductive activity (March), second half of reproductive activity (May) and beginning of photorefractoriness (July). Isolated Leydig cells were incubated with LH as well as genistein, daidzein, equol and coumestrol and the concentration of testosterone in the medium was determined by radioimmunoassay. The mean weight of testes from ganders in May and July decreased relative to their weights in March, but no significant differences among experimental groups were noted. No differences were observed in basal and LH-stimulated testosterone secretion by Leydig cells of ganders fed the control diets and the diets with higher phytoestrogen content. In July, LH did not stimulate testosterone secretion in either group. In vitro treatment with genistein, daidzein and equol (5 and 50 microM) inhibited basal and LH-stimulated testosterone production by Leydig cells from both groups. Coumestrol (5 and 50 microM) inhibited basal testosterone secretion only in March in the control group. Dietary exposure to phytoestrogens had a slight effect on in vitro testicular secretion in ganders. In vitro treatment with phytoestrogen inhibited testosterone production by Leydig cells. Genistein showed the strongest effect and coumestrol had the weakest influence on testicular secretion.

Animal Feed↗
PubMed1995

Altered time course of urinary daidzein and genistein excretion during chronic soya diet in healthy male subjects.

Soybean consumption is associated with reduced rates of prostate and other cancers, possibly due in part to the presence of isoflavones. The metabolism and disposition of these soya-derived phytoestrogens after chronic soya exposure were studied on a metabolic unit in six healthy males (21-35 yrs of age) who consumed an unrestricted hospital diet and a 12-oz portion of soymilk with each meal for one month. The daily isoflavone intake was about 100 mg of daidzein (mostly as diadzin) and about 100 of mg of genistein (mostly as genistin). At two-week intervals, excretion of isoflavones in urine was studied, during which time the subjects consumed a constant basal diet for three to four days, ingested the full daily 36-oz portion of soymilk within 30 minutes each day for one to two days, and collected urine continuously. The urinary recovery of ingested diadzin plus daidzein (46.9 +/- 15.2%, mean +/- SD) and genistin plus genistein (14.6 +/- 9.2%) did not change with prolonged soya ingestion. The absorption half-lives (t1/2) for daidzein and genistein and the appearance t1/2 for equol (1 subject) were initially 1.5 +/- 0.4, 1.9 +/- 0.6, and 2.2 hours, respectively, and 2.5 +/- 1.1 (p = 0.06 compared with baseline) 1.4 +/- 0.9 (p = 0.03) compared with baseline), and 4.2 hours, respectively, during one month of soymilk ingestion. The excretion t1/2 for daidzein, genistein, and equol were initially 2.9 +/- 0.5, 3.8 +/- 0.7, and 5.2 hours, respectively, and 3.9 +/- 1.2 (p - 0.03), 5.5 +/- 1.6 (p = 0.02), and 9.7 hours, respectively, during one month of soymilk ingestion. These results indicate that chronic soya exposure did not induce significant changes in the metabolic pathways of isoflavones but altered the time courses of daidzein and genistein excretion. Thus chronic exposure to soya might prolong the tissue exposure to the presumed biologically active free and unconjugated forms of these isoflavones and thereby enhance their oncoprotective effects.

Absorption↗
PubMed1997

Estrogenic and antiproliferative properties of genistein and other flavonoids in human breast cancer cells in vitro.

Experimental and epidemiologic studies support the view that soyfoods prevent cancer as well as diseases and symptoms associated with estrogen deficiency. Recent research suggests that the isoflavonoid genistein, a phytoestrogen found in abundance in soyfoods, may be one of the principal molecular components responsible for these health benefits. In this study we investigated the effects of a broad physiologically relevant concentration range of genistein on estrogen receptor (ER) binding, induction of the estrogen-regulated antigen pS2, and cell proliferation rate in ER(+) and ER(-) human breast cancer cells grown in vitro. Dose response to genistein was compared with that of estradiol, tamoxifen, and several other structurally similar iso- and bioflavonoids (e.g., equol, kaempferol, and quercetin). Our results revealed that genistein has potent estrogen agonist and cell growth-inhibitory actions over a physiologically achievable concentration range (10 nM-20 microM). Other flavonoids over the same concentration range were good estrogen agonists and poor cell growth inhibitors (equol) or poor estrogen agonists and potent growth inhibitors (kaempferol and quercetin). The growth-inhibitory actions of flavonoids were distinctly different from those of triphenyl antiestrogens like tamoxifen. In summary, our results reveal that genistein is unique among the flavonoids tested, in that it has potent estrogen agonist and cell growth-inhibitory actions over a physiologically relevant concentration range.

Anticarcinogenic Agents↗
PubMed1998

Daidzein conjugates are more bioavailable than genistein conjugates in rats.

This study compared the bioavailability of conjugates of the soy isoflavones genistein and daidzein in rats. Rats were given a single oral dose of a soy extract that provided 74 micromol genistein and 77 micromol daidzein/kg body wt (as conjugates). Plasma samples were obtained from treated and untreated rats; urine and fecal samples were obtained before and after treatment. Isoflavones, equol (the main end product of bacterial degradation of daidzein), and 4-ethyl phenol (the main end product from genistein) were measured by HPLC. The plasma daidzein concentration was maximal at 2 h (9.5 +/- 0.71 micromol/L) and was almost double that of genistein (P = 0.009). Between 2 and 15 h, the plasma daidzein concentration declined by 32%, but the concentration of genistein changed little. At 15 h, the concentrations of daidzein and genistein were not significantly different. Urinary excretion of daidzein over the 48-h postdose period was 17.4 +/- 1.2% of the dose, but only 11.9 +/- 1.1% of the genistein dose was excreted in urine. Equol excretion was 5.0 +/- 1.5% of the daidzein dose, but 41.9 +/- 5.0% of the genistein dose was excreted as 4-ethyl phenol. Fecal daidzein accounted for 2.3 +/- 0.5% and fecal genistein for 3.4 +/- 0.4% of the respective doses. It is concluded that conjugates of daidzein are more bioavailable than those of genistein, probably because of the greater resistance of the former to degradation by gut bacteria.

Administration, Oral↗
PubMed2004

Influence of 10 wk of soy consumption on plasma concentrations and excretion of isoflavonoids and on gut microflora metabolism in healthy adults.

BACKGROUND: Little information is currently available on the role of the gut microflora in modulating isoflavone bioavailability or on sex differences in isoflavone metabolism and bioavailability. OBJECTIVE: We sought to determine whether chronic soy consumption influences isoflavone bioavailability as judged by plasma isoflavone concentrations and modified gut microflora activities [beta-glucoside hydrolysis and equol and O-desmethylangolensin (O-DMA) production]. We also examined whether sex differences in isoflavone metabolism exist. DESIGN: A randomized, parallel, controlled study design was used to compare a high-soy diet (104 +/- 24 mg total isoflavones/d) with a low-soy diet (0.54 +/- 0.58 mg total isoflavones/d) in 76 healthy young adults for 10 wk. RESULTS: Concentrations of isoflavones and their gut microflora metabolites in the plasma, urine, and feces were significantly higher in the subjects who consumed the high-soy diet than in those who consumed the low-soy diet. Concentrations of O-DMA in plasma and urine were higher in the men than in the women. Fecal bacteria from subjects consuming both diets could convert daidzein to equol ex vivo. Fecal beta-glucosidase activity was significantly higher in the subjects who consumed the high-soy diet than in those who consumed the low-soy diet. CONCLUSIONS: Although interindividual variation in isoflavone metabolism was high, intraindividual variation was low. Only concentrations of O-DMA in plasma and urine appeared to be influenced by sex. Chronic soy consumption does not appear to induce many significant changes to the gut metabolism of isoflavones other than higher beta-glucosidase activity.

Adolescent↗
PubMed2006

Bioavailability of isoflavones after ingestion of soy beverages in healthy adults.

It is unknown whether the bioavailability of isoflavones is affected by the concomitant ingestion of glucosides or aglycones. This study was designed to investigate the effects of soymilk-based beverages containing different types of isoflavones on their absorption, excretion, and metabolism. Twelve healthy volunteers consumed 3 kinds of soymilk: untreated soymilk, beta-glucosidase-treated soymilk, and fermented soymilk. Blood samples were collected after 0, 1, 2, 3, 4, 5, 6, 7, 8, and 24 h. Urine samples were collected from 0 to 48 h. Concentrations of isoflavones and daidzein metabolites in serum and urine were measured by liquid chromatography-mass spectrometry. After the ingestion of soymilk, the total concentration of isoflavones in serum rose slowly and reached a maximum of 0.94 +/- 0.39 micromol/L at 6.0 +/- 1.2 h. However, beta-glucosidase-treated soymilk and fermented soymilk increased the serum isoflavone concentration significantly more quickly with maximum concentrations at 1.0 h of 1.75 +/- 0.33 micromol/L and 2.05 +/- 0.32 micromol/L, respectively. The urinary excretion of isoflavones after ingesting of these aglycone-enriched preparations was significantly greater than after consumption of untreated soymilk up to 8 h after injection, but not thereafter. The total and individual concentrations of isoflavones in serum and urine did not differ when subjects consumed the 2 aglycone-enriched soymilks. However, in equol producers (n = 5), the ingestion of ESM tended to increase urinary excretion of equol compared with the consumption of FSM (P = 0.08). These results demonstrated that the isoflavone aglycones of soymilk were absorbed faster and in greater amounts than their glucosides in healthy adults and that the metabolism of isoflavones might be affected by the type of soymilk consumed.

Adult↗
PubMed1999

Phytoestrogens inhibit growth and MAP kinase activity in human aortic smooth muscle cells.

-Estrogens are known to induce cardioprotective effects by inhibiting smooth muscle cell (SMC) growth and neointima formation. However, the use of estrogens as cardioprotective agents is limited by carcinogenic effects in women and feminizing effects in men. If noncarcinogenic and nonfeminizing estrogenlike compounds, such as natural phytoestrogens, afford cardioprotection, this would provide a safe method for prevention of cardiovascular disease in both men and women. Therefore, we evaluated and compared in human aortic SMCs the effects of phytoestrogens (formononetin, genistein, biochanin A, daidzein, and equol) on 2.5% fetal calf serum-induced proliferation (3H-thymidine incorporation and cell number), collagen synthesis (3H-proline incorporation), and total protein synthesis (3H-leucine incorporation) and on PDGF-BB (25 ng/mL)-induced migration (modified Boydens chambers). Moreover, the effects of phytoestrogens on PDGF-BB (25 ng/mL)-induced mitogen-activated protein kinase (MAP kinase) activity in SMCs was also studied. Phytoestrogens inhibited proliferation, collagen and total protein synthesis, migration, and MAP kinase activity in a concentration-dependent manner and in the following order of potency: biochanin A>genistein>equol>daidzein>formononetin. In conclusion, our studies provide the first evidence that in human aortic SMCs phytoestrogens inhibit mitogen-induced proliferation, migration and extracellular matrix synthesis and inhibit/downregulate MAP kinase activity. Thus, phytoestrogens may confer protective effects on the cardiovascular system by inhibiting vascular remodeling and neointima formation and may be clinically useful as a safer substitute for feminizing estrogens in preventing cardiovascular disease in both women and men.

Adult↗
PubMed2006

Phyto- and endogenous estrogens differently activate intracellular calcium ion mobilization in bovine endometrial cells.

The main purpose of this study was to check whether phyto- and endogenous estrogens influence calcium ion mobilization [Ca(2+)](i) in bovine endometrial cells and whether this action is connected with biological effects i.e. prostaglandin (PG)F(2alpha) production. In our study we used two calcium measurement methods by comparing the microscopic method with widely used quantitative - spectrofluorometric method of [Ca(2+)](i) measurement. We also wanted to confirm whether visualization of calcium ion [Ca(2+)](i) in cells using microscopic method supported by micro image analysis (Micro Image Olympus system) reflects real, qualitative changes in the ion concentration. In both methods a cell-permeable form of fluorescent [Ca(2+)](i) indicator Fura-2 was used. Cultured bovine endometrial epithelial and stromal cells influenced by phorbol-2-myristate-13-acetate (PMA; positive control), estradiol 17-beta (E(2); endogenous estrogen) and active metabolites of phytoestrogens (environmental estrogens) were used as a model to study PGF(2alpha) secretion and [Ca(2+)](i) mobilization in the cells. Equol and para-ethyl-phenol in doses of 10(-8)-10(-6) M increased PGF(2alpha) concentration both in epithelial and stromal cells (P<0.05). In both methods, equol and para-ethyl-phenol did not cause intracellular [Ca(2+)](i) mobilization in epithelial and stromal cells (P>0.05). Both methods revealed that only E(2) and PMA induced intracellular [Ca(2+)](i) mobilization in epithelial and stromal cells (P<0.05). The results of both methods were highly correlated (P<0.001; r=0.82 for epithelial cells and r=0.89 for stromal cells). In conclusion, both methods gave approximately the same results and showed that phytoestrogens, in contrast to PMA and E(2), did not cause intracellular [Ca(2+)](i) mobilization in endometrial cells. The obtained results proved that the [Ca(2+)](i) visualization method supported by micro image analysis can produce similar results to the spectrofluorometric method.

Animals↗
PubMed1998

Phytoestrogens: dietary intake and excretion in postmenopausal Chinese women.

OBJECTIVES: The aims of this study were to estimate the dietary intake of phytoestrogens and to measure urinary phytoestrogen excretion in postmenopausal Chinese women. METHODS: Postmenopausal Chinese women were recruited from the hormone replacement clinic of the Prince of Wales Hospital. Dietary intake of phytoestrogen-rich foods was estimated using a food frequency questionnaire. Urinary output of the isoflavonoids daidzein and genistein and the metabolite of daidzein, equol, was measured using high-performance liquid chromatography. RESULTS: The mean daily excretion of daidzein, genistein and equol was 3.24 (+/- 3.63), 1.47 (+/- 1.75) and 0.64 (+/- 1.53) mumol, respectively. The total mean daily isoflavonoid excretion was 5.36 (+/- 5.27) mumol. CONCLUSIONS: Urinary excretion of isoflavonoid phytoestrogens in this Chinese population was lower than that reported in Japanese subjects. This may be due to the higher consumption of legumes, especially soy products, in the Japanese compared to the Chinese diet. The intake of green vegetables was higher in the Chinese subjects, and this food group may be the main contributor to their total phytoestrogen intake.

Adult↗
PubMed2000

[Phytoestrogens].

Epidemiological studies revealed that foodstuffs, in particular, soy foods containing isoflavonoid phytoestrogens may reduce the risk of some hormone-dependent disease such as not only postmenopausal symptoms but also certain(breast, prostate and colon) cancers and cardiovascular disease. This review introduces the metabolism of soybean isoflavonoids by human intestinal bacteria and the binding and gene-expression activity of the metabolites towards the human estrogen receptor(hER) alpha and beta. The dietary isoflavones(daidzin and genistin) in soybean were metabolized to equol and dihydrogenistein via daidzein and genistein, respectively. The metabolites bind more strongly to hER beta than hER alpha. The binding affinity of genistein is comparable that of 17 beta-estradiol. Equol induces transcription most strongly both with hER beta and hER alpha.

Bacteria↗
PubMed2004

Effects of isoflavone supplements on bone metabolic markers and climacteric symptoms in Japanese women.

A double-blind, placebo-controlled crossover study on the effects of 40~mg/d isoflavone supplements was carried out by 58 climacteric Japanese women. A questionnaire and an interview concerning climacteric symptoms, health status, dietary and exercise habit, and medical history were carried out, and the physical check-up and biochemical tests including sex-hormone analysis were made at baseline and after 4 and 8 weeks of treatment. Urinary isoflavones were separately measured from the frozen samples. Isoflavone treatment did not cause any adverse effects on anthropometric measures or blood chemistry. Urinary deoxypyridinoline, a marker of bone resorption decreased significantly with isoflavone treatment. This tendency was remarkable among equol producers. Plasma osteocalcin and bone mineral density did not change by the four-weeks treatment. As for climacteric symptoms, hot flash decreased significantly. Systolic and diastolic blood pressure of hypertensive participants decreased significantly after isoflavone treatment compared with baseline and the placebo treatment. Isoflavone supplementation offers benefits to reduce effectively on bone resorption enhanced by menopause. The treatment also showed an improvement of climacteric hot flash and hypertension. Equol producers showed better results.

Adult↗
PubMed2006

Plasma and prostate phytoestrogen concentrations in prostate cancer patients after oral phytoestogen supplementation.

BACKGROUND: Phytoestrogens have been suggested to reduce the risk of prostate cancer (CaP), but no data exists on how oral phytoestrogen supplementation influences phytoestrogen concentrations in prostate tissue. METHODS: Forty men with CaP, assigned for radical prostatectomy, received 240 mg of clover phytoestrogens or placebo daily for a 2-week period before their operation in a prospective and randomized study. Phytoestrogens were measured in plasma and prostate tissue by time-resolved fluoroimmunoassay (TR-FIA). RESULTS: All patients had low baseline phytoestrogen concentrations and only 35% had a detectable plasma concentration of equol. Oral supplementation with phytoestrogens induced a statistically significant (P<0.001) 23- and 7-fold increase in prostate tissue concentrations of the phytoestrogens genistein and daidzein, respectively. Supplemented patients demonstrated prostate tissue genistein and daidzein concentrations that were over twofold higher than their plasma. Interestingly, even though the placebo group did not receive phytoestrogen challenge, they also demonstrated twofold prostate tissue genistein and daidzein concentrations compared to their plasma values, suggesting that the prostate can concentrate available phytoestrogens. In addition, after the supplementation, 90% of the supplemented patients had a detectable plasma equol concentration. CONCLUSIONS: We conclude that prostate tissue can concentrate genistein and daidzein. Significant elevation of intraprostatic genistein and daidzein concentrations can be achieved with a short-term dietary phytoestrogen supplementation.

Administration, Oral↗
PubMed2006

Prostatic fluid concentrations of isoflavonoids in soy consumers are sufficient to inhibit growth of benign and malignant prostatic epithelial cells in vitro.

BACKGROUND: The differential intestinal metabolism of the soy isoflavones is likely to influence the ability of soy to prevent prostate cancer. While daidzein, genistein, and equol have direct antiproliferative effects on prostatic epithelial cells in vitro, there are no such data for the isoflavone glycitein, or seven metabolites: O-desmethylangolensin (ODMA), 6-hydroxyODMA (6H-ODMA), dihydrodaidzein (DHD), cis-4-hydroxyequol (C4HE), 3'-hydroxydaidzein (3HD), 6-hydroxydaidzein (6HD), and 8-hydroxydaidzein (8HD). In the current study, the in vitro activities of these compounds were elucidated, and the active ranges of concentrations were compared to that found in Caucasian prostatic fluid (PF) and plasma samples. METHODS: The effects of isoflavonoids on cell growth, cell cycle distribution, and apoptosis (active Caspase 3) were examined on benign prostatic epithelial cells (PrEC), and the prostate cancer cell line LNCaP. RESULTS: PF concentrations of genistein, equol, and daidzein (but not ODMA or DHD) were often within the ranges that reduce PrEC growth in vitro. Profound differences in sensitivities were observed with LNCaP. The hydroxydaidzeins, C4HE, and 6H-ODMA had significant inhibitory effects at 10(-5)M on PrEC growth (but not LNCaP). Glycitein had significant effects on both. Reductions in cell growth were typically associated with both changes in cell cycle distribution and Caspase 3 activation. When five isoflavonoids were used in combination at concentrations present in PF samples, synergistic effects were observed. CONCLUSION: The profound differences in sensitivities of prostatic epithelial cells to these compounds along with their synergistic effects suggest that multiple metabolites in vivo may be optimal for preventing prostate cancer.

Cell Division↗
PubMed2003

Quantification of isoflavones and lignans in serum using isotope dilution liquid chromatography/tandem mass spectrometry.

Phytoestrogens (isoflavones and lignans) are receiving increasing attention due to a potential protective effect against a number of complex diseases. However, in order to investigate these associations, it is necessary to accurately quantify the levels of phytoestrogens in foods and biological fluids. We report an assay for three isoflavones (daidzein, genistein, and glycitein), two metabolites of daidzein (O-desmethylangolensin and equol), and two lignans (enterodiol and enterolactone) in human serum using electrospray ionisation liquid chromatography/mass spectrometry (LC/MS) with selective reaction monitoring. A simple, highly automated sample preparation procedure requires only 200 microL of sample and utilises one solid-phase extraction stage. Limits of detection are in the region of 10 pg/mL for all analytes except equol, which had a limit of detection of approximately 100 pg/mL. The method developed is suitable for measuring the concentrations of phytoestrogens in blood samples collected from large epidemiological studies. The results of the analysis of serum samples from 300 men and women living in the UK are reported.

Calibration↗
PubMed2002

Effects of dietary phytoestrogens in vivo and in vitro in rainbow trout and Siberian sturgeon: interests and limits of the in vitro studies of interspecies differences.

A study of the effects of dietary genistein on trout and sturgeon in vivo showed that sturgeon was sensitive to 20 ppm of genistein, whereas trout was not. To analyze the origin of this interspecies difference in sensitivity, a cell culture technique was developed with hepatocytes from sturgeon and compared to results obtained with hepatocytes from trout in the same system. The hepatocyte culture proved to be useful as bioassay for estrogenicity. Vitellogenin (VTG), assayed by a specific enzyme-linked immunosorbent assay, was used as a biomarker of the estrogenic activity. 17 beta-Estradiol, its glucuronide and sulfate derivatives, and estradiol analogues (ethynylestradiol and diethylstilbestrol) were tested. Nonestrogenic compounds such as androgens, progesterone, and cortisol were tested as negative controls. VTG production was monitored at doses ranging from 1 nM to 10 microM estradiol. Phytoestrogens, from the isoflavone family, were tested individually at increasing doses exhibiting dose response curves for concentrations from 500 nM to 10 microM. With tamoxifen, an antagonist of estrogen receptors, the estrogenic effect was partially reduced. The effect was the same with ICI182,780 in sturgeon, whereas the effect was the opposite in trout. The estrogenic potency of the isoflavones ranged differently between the two species in the following order: biochanin A < daidzein = formononetin < genistein < equol in trout and biochanin A < genistein < daidzein < formononetin < equol in sturgeon. Further, in sturgeon, formononetin was the most potent phytoestrogen in vitro, whereas its activity was weakest in vivo. These data suggest that one must reconsider the relevance of heterologous estrogenic tests and of homologous in vitro tests for estrogenic potency of chemicals.

Animals↗
PubMed1995

Lignan and isoflavonoid conjugates in human urine.

Lignans and isoflavonoids are two groups of diphenolic phytoestrogens of plant origin which have gained increasing interest because of their possible cancer protective properties. High excretion of these compounds occur in populations at low risk of breast, prostate and colon cancer consuming either high amounts of whole-grain (lignans and some isoflavonoids) or soy products (isoflavonoids and some lignans). We determined the pattern of conjugation of the phytoestrogens in four urine samples from vegetarian or semivegetarian women and in two samples from men. Seven compounds were investigated: enterodiol, enterolactone, matairesinol, diadzein, equol, genistein and O-desmethylangolensin. The fractions quantified are the free fraction, mono- and disulfate, as well as the mono-, di- and sulfoglucuronide fractions. For the fractionation and purification we used ion-exchange chromatography and the determination of the concentrations of each compound in all fractions was done by isotope dilution gas chromatography-mass spectrometry (GLC-MS) using deuterated internal standards of all diphenols. More than 60% of all compounds determined, occurred in the monoglucuronide fraction. Daidzein, enterodiol and equol are excreted to a relatively high extent as sulfoglucuronides and genistein as diglucuronide. We conclude that the general pattern of lignan and isoflavonoid conjugates in urine is similar to that of endogenous estrogens.

Estrogens↗