Plasma Levels Of Estrone Sulfate Research Articles

Hepatic Gene Expression and Metabolite Profiles of Androstenone and Skatole Relative to Plasma Estrone Sulfate Levels in Boars.

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.

Effect of one-month treatment with vaginal promestriene on serum estrone sulfate levels in cancer patients: A pilot study

Vaginal promestriene was tested in gynecological cancer patients who suffered from severe vaginal dryness and dyspareunia. This form of estrogen has a low level of vaginal absorption and proved to be effective for vaginal atrophy. Method17 patients were treated with a 10mg soft vaginal suppository daily for one month. Plasma levels of estrone sulfate (E1S), used as the marker of overall estrogenicity, were measured by liquid chromatography in combination with mass spectrometry. ResultsMean E1S levels changed from 533 (22–2920) to 374 (81–856) pg/ml (p=0.39). ConclusionIn highly symptomatic gynecological cancer patients the level of circulating estrone sulfate was not significantly affected by vaginal promestriene treatment overall, but a wide range of levels was noted pre and post treatment in individual patients.

Effects of body mass index (BMI) on plasma levels of estrone sulfate (ES) in postmenopausal women with breast cancer (BC) during letrozole (L) treatment.

515 Background: BMI is associated with an increased risk of BC in postmenopausal women. Moreover, BC overweight women have poorer prognosis compared to women with normal weight. Data from ATAC (the anastrozole, tamoxifen alone or in combination study) trial reported that obesity reduce the efficacy of the aromatase inhibitor (AI) anastrozole in early BC. One possible explanation is that higher estrogens levels resulting from high BMI may lead to lower efficacy of the AI treatment. No clear data are available about the effects of BMI on estrogen circulating levels during AI treatment, and if the increase of AI dosage may result in more complete estrogen suppression in overweight women. Methods: We evaluated the correlation between BMI and plasma concentration of ES in postmenopausal women with early BC during adjuvant treatment with L (2.5 mg/die). Patients were participating in two prospective Italian clinical trials (GIM4 and GIM5) evaluating L treatments after adjuvant tamoxifen. Plasma samples were obtainedafter at least six weeks of L therapy. After a non-chromatographic cleaning procedure of samples, plasma ES levels were evaluated by RIA. Ln values for plasma ES were used for statistics. Geometricmeans and 95% confidence interval (CI) were used as summary measures. Results: ES plasma concentration and BMI were evaluated in 370 women. Median treatment duration was 49wks (range 6-201wks). Median age of patients was 60 yrs (range 34-84 yrs). Table shows data regarding ES concentrations and BMI of patients. Conclusions: Circulating ES levels during L (2.5 mg/die) treatment were super imposable in all BMI groups. Our data indicate that whether BMI influences AI efficacy, this is not due to an insufficient suppression of aromatase activity in women with higher BMI. Increasing the dose of AI to further reduce ES levels in high BMI patients is a questionable way to increase AI efficacy. BMI, kg/m2 No. of pts % ES geom mean (pg/mL) 95% CI <23.0 85 23 21.7 21.2-22.5 23.0-24.9 65 18 20.2 19.6-20.9 25.0-27.9 111 30 24.2 23.8-24.6 28.0-29.9 43 12 22.5 21.5-23.6 >30.0 66 17 19.8 19.2-20.4

Single-nucleotide polymorphisms (SNPs) of CYP19A1 and plasma levels of estrone sulfate (ES) in postmenopausal women with breast cancer (BC) during letrozole (L) treatment.

2606 Background: The efficacy of aromatase inhibitors in breast cancer patients might be related to various SNPs of CYP19A1 gene (encoding aromatase enzyme), determining a different suppression of ...

Plasma levels of estrone sulfate (ES) in postmenopausal women with breast cancer (BC) during letrozole (L) treatment: Association with single nucleotide polymorphisms (SNPs) of CYP19A1

555 Background: The CYP19A1 gene encodes aromatase, a key enzyme for estrogen biosynthesis. We investigated the association between four CYP19A1 SNPs, affecting different circulating estrogen levels (rs10046 C&gt;T, rs4646 G&gt;T, rs749292 C&gt;T, rs727479 T&gt;G), and suppression of plasma ES levels induced by 6 weeks (time needed to reach L steady-state concentrations) of L (25 mg/d). Methods: Patients were enrolled into a prospective, italian multi-centre trial (GIM5) testing the correlation of CYP19A1 SNPs with the efficacy of L adjuvant therapy, after 5 years of tamoxifen, in postmenopausal early BC patients. Blood samples for hormone measurements were obtained immediately before starting L (baseline) and following 6 wks of treatment. SNPs were identified from DNA obtained from peripheral blood cells by Hexaprimer Amplification Refractory Mutation System PCR (H-ARMS-PCR). Plasma ES levels were evaluated by Radio Immuno Assay (RIA). Results: SNPs and hormone levels were evaluated in at least 129 patients. SNPs of CYP19A1 were associated with different baseline plasma ES levels. Mean inhibition of aromatase activity induced by L ranges from 71% to 79%, as a function of the SNPs. After 6 weeks of L no difference in ES levels was observed between patients with different SNPs (Table). Conclusions: L therapy induces a higher aromatase suppression in patients with SNPs associated with higher baseline plasma ES levels. The difference in ES levels associated with genetic variation at the CYP19A1 locus disappeared after L therapy. [Table: see text] [Table: see text]

Relationship between metabolism of androstenone and skatole in intact male pigs.

The relationship between the metabolism of androsterone and skatole, the major compounds responsible for boar taint, was investigated in F4 Swedish Yorkshire x European Wild Pig intact males. The metabolism of androstenone and skatole were studied in liver microsomes, and the testicular steroid production was measured in testes microsomes. Including androstenone in the assays of skatole metabolism reduced the formation of 6-hydroxyskatole (pro-MII), and three other skatole metabolites (P<.05). The formation of three additional metabolites was not affected. Liver microsomal incubations of androstenone produced two metabolites, I and II. The rate of the formation of metabolite I and the rate of androstenone metabolism were correlated with the rate of skatole metabolism. Liver metabolism of androstenone was not related to levels of androstenone in fat. Testicular synthesis of 16-androstene steroids was correlated with combined synthesis of estrogens and androgens, plasma levels of androstenone, levels of skatole in fat, and skatole metabolism in the liver (P<.05). Plasma levels of estrone sulfate were correlated with levels of skatole in fat and with androstenone levels in fat and plasma and were negatively correlated with synthesis of skatole metabolite F-1 and pro-MII sulfation. These results indicate that the liver metabolism of androstenone and skatole are related. However, it is likely that the relationship between levels of androstenone and skatole in fat is due more to a link between the testicular synthesis of androstenone rather than to the metabolism of androstenone and skatole in the liver. Sex steroids may affect this relationship because of their biosynthesis along with androstenone and possible inhibition of skatole metabolism in the liver.

Agonadal presumptive XX/XY leukochimeric pig.

XX/XY chimeric pigs are uncommon and their reproductive anatomy is variable and unpredictable. A piglet was identified by its enlarged vulva as a possible intersex. Venous blood was collected at 1.5 and 9 months for karyotyping and determination of testosterone and estrone sulphate concentrations. At 1 year euthanasia was performed. The reproductive tract was carefully dissected and examined histologically. As the animal matured the vulva did not develop relative to the size of the animal. Lymphocyte cultures indicated a 70% XX/30% XY chimera. The reproductive tract consisted of a strand of tissue enveloped by fascia. Histological study revealed presumptive Wolffian derivatives, coiled bilateral ducts along the tract, and a Müllerian derivative, a medially located duct in the caudal third of the tract. No gonads were found. Plasma levels of estrone sulfate and testosterone were negligible. In utero exposure to exogenous androgens from a male co-twin or weak endogenous adrenal androgens may account for the enlarged vulva at birth and retention of the androgen dependent Wolffian duct primordia. An atesticular state is supported by retention of the Müllerian duct primordia and the negligible peripheral sex steroids.

Numerical Variations among Blood Mononuclear Cells during the Peripartal Period in the Gilt

Numerical variations among mononuclear cells (MNC) were studied in blood collected from nine cross-bred primiparous gilts during two weeks before and two weeks after parturition. Simultaneously, the plasma levels of cortisol and oestrone sulphate were measured. The number of polymorphonuclear cells (PMNs) increased significantly (p less than 0.05) at parturition, while the number of MNCs decreased significantly (p less than 0.01) at the same time. Concomitantly with the total number of MNCs, the proportion of Ig-bearing MNC (Ig(+)-cells) also decreased significantly (p less than 0.01). No considerable variations of the proportion of MNCs expressing MHC Class II antigen could be seen throughout the study. The proportion of MNC with receptor for the Fc-part of IgG decreased significantly (p less than 0.01) during the week preceding parturition, but increased (p less than 0.05) again at parturition. The proportion of Ig(+)-cells was positively correlated both to the plasma level of oestrone sulphate and cortisol, while the number of Ig(+)-cells was only positively correlated to the level of cortisol. Thus, the study shows considerable numerical variations within the leukocyte sub-populations in the gilt around parturition.

A Direct Assay for Oestrone Sulphate and Its Use to Investigate the Effect of Ampicillin on Plasma Levels of Oestrone Sulphate

A direct radioimmunoassay for measuring plasma levels of oestrone sulphate has been developed using 8-anilino-2-naphthalene sulphonic acid to displace oestrone sulphate from plasma binding proteins. Oestrone sulphate was assayed by using an antiserum raised against glucuronide which cross-reacted 100% with oestrone sulphate. The direct assay gave a good analytical recovery of oestrone sulphate and there was a good correlation (r = 0.82, P less than 0.001) for plasma levels of oestrone sulphate measured by the direct assay and a method involving steroid conjugate extraction and enzyme hydrolysis. The mean (+/- S.D.) plasma level of oestrone sulphate in men was 1100 +/- 280 pg/ml. The effect of taking the antibiotic, Ampicillin, on plasma levels of oestrone sulphate was investigated in four men. Plasma levels of oestrone sulphate were significantly reduced after taking Ampicillin for 5 days. Ampicillin may act to lower plasma levels of oestrone sulphate by reducing the growth of bacteria in the gut or by inhibiting oestrogen sulphotransferase activity.

Hepatic oestrone sulphotransferase activity and plasma levels of oestrone sulphate, oestrone and oestradiol in male guinea pigs with fatty liver.

Fatty liver was induced in male guinea pigs by combined administration of carbon tetrachloride and azathioprine from the 3rd to 15th week of age. The final body and liver weights were significantly lower than in the control animals, whereas the liver weight in percentage of total body weight was equal. The protein concentration in the 105,000 X g cytosol fraction from the livers was significantly lower than in controls (2P less than 0.02). The oestrone sulphotransferase activity was studied by measuring the oestrone sulphate production when incubating oestrone, PAPS + [35S]PAPS and liver cytosol for 1 h. Significantly less oestrone sulphate per mg protein, per gram liver tissue or total liver was produced with cytosol from animals with fatty liver than from controls (2P less than 0.02). In accordance with decreased oestrone sulphotransferase activity, animals with fatty liver revealed significantly lower plasma levels for oestrone sulphate (2P less than 0.02), whereas the plasma levels for oestrone and oestradiol were increased (2P less than 0.02). The present study supports the assumption of decreased oestrone sulphotransferase activity being important for the changes in plasma oestrogens seen in alcoholic men with fatty liver.

Concentrations of Oestrone and Oestradiol‐l 7β in the Peripheral Plasma of the Nanny Goat during the Oestrous Cycle, Gestation and Puerperium

Contents: The changes in the plasma levels of oestrone sulphate and oestradiol‐17β during the oestrous cycle, gestation and puerperium in the goat are described. The oestrone sulphate concentrations remained fairly constant (250–350 pg/ml) throughout the oestrous cycle until day 20 when a sharp increase of the oestrone sulphate plasma levels occurred in pregnant goats which became significantly different at day 38 of gestation from nonpregnant values. Oestradiol‐17β plasma levels were significantly lower at days 17–20 in pregnant than in nonpregnant does. Oestrone sulphate and oestradiol‐17β concentrations rose until the 12th week of gestation and then declined to about 50% of the former ranges of concentrations before rising again to high values at weeks 17–20 of gestation. Increasing plasma levels of oestrone sulphate and oestradiol‐17β were determined during the last ten days preceding parturition. The concentrations of oestrone sulphate returned to basal levels by the 2nd—4th day post partum whereas oestradiol‐17β values reached base values 24 hours after parturition. Both oestrogen concentrations remained constant during the puerperium until day 51 post partum.

Oestrone sulphate levels in plasma of sows as a basis for prediction of litter size at term

This study examines relationships between litter size at term and plasma levels of oestrone sulphate in sows between days 22 and 33 after mating. In 1948 animals tested, significant ( P<0.0001) correlations were found between litter size and levels of oestrone sulphate in plasma collected from sows on days 22–29 of gestation. Of four correlations examined, a rising exponential function (not forced through the origin) yielded the lowest root mean square residuals. Maximum levels of oestrone sulphate in plasma of 23 unmated sows were 1.9 n M; only five sows farrowed with oestrone sulphate values below this level. Plasma oestrone sulphate levels which were derived to identify sows with a <5% likelihood of farrowing exceeded 1.9 n M, actual values being dependent upon the number of days lapsed between mating and blood sampling. The results of this study indicate that, by specifying the day of blood sampling, measurement of oestrone sulphate levels in plasma collected from sows between days 22 and 29 after mating can be used to provide early identification of non-pregnant animals, prediction of litter size in sows which are pregnant, and diagnosis of low fecundity in the short term.

Steroid sulfatase activities in normal and cirrhotic livers and plasma levels of estrone sulfate, estrone and estradiol-17β in men

Estrone and dehydroepiandrosterone (DHEA) sulfatases were studied in livers of normal and cirrhotic men. Their Km were 3.2μM and 1.2μM respectively. The musomal sulfatases were solubilized by Miranol H2M and ultrasound. After gel filtration, the soluble material gave a single peak of activity for both substrates with a molecular weight of approximately 330,000. In terms of pmol of product.min −1 per mg of fresh tissue, the mean (±SD) values of estrone and DHEA sulfatase activities were lower in cirrhotic livers [(n=7) (4.09±2.90 and 0.38±0.20)] than in normal livers [(n=13)(8.29±4.00 and 0.69±0.20)]. The differences were statistically significant: p<0.03 for estrone sulfatase and p<0.01 for DHEA sulfatase. In cirrhotic men, the mean level of plasma estrone is increased whereas that of estrone sulfate is decreased. The variations may be related to the decrease of serum albumin in cirrhotic subjects.

Concentrations of oestrone sulphate, androgens and LH in the peripheral plasma of mating stallions

Summary. Peripheral plasma levels of oestrone sulphate, androgens and LH were studied in two mating stallions. A peak of oestrone sulphate was observed 7·5–15 min after exposure to an oestrous female. No variations were recorded in LH concentrations. The concentrations of testosterone, dihydrotestosterone and androstenedione increased similarly after mating and on a day of sexual inactivity.

Simulation of pregnancy levels of plasma oestrone sulphate by infusion in the non-pregnant mare: A preliminary study

Oestrone sulphate was infused intravenously in saline solution into two, non-pregnant pony mares in repeated trials to simulate levels of the oestrogen found in plasma after midpregnancy in mares. Rates of infusion of oestrone sulphate ranged from 32 to 231 mg of oestrone equivalent per hour. Blood samples were taken from the opposite jugular vein for measurement of oestrone sulphate by radioimmunoassay. Plasma levels rose rapidly from the start of each infusion of the oestrogen and remained elevated over the hour-long periods, with concentrations as oestrone ranging from about 175 to 700 ng/ml. During each subsequent infusion with saline alone the oestrogen levels in plasma fell within 1 h to about 25% of the preceding values. Results were similar for each animal and simulation of plasma levels of oestrone sulphate in pregnancy was achieved.

Plasma levels of estrone sulfate, free estrogens and progesterone in the pregnant ewe throughout gestation

Plasma levels of estrone sulfate, estrone and estradiol, and progesterone were measured in six ewes throughout pregnancy. Estrone sulfate was detectable at around 70 days of gestation with values ranging between 0.3 – 0.7 pmol (0.1 – 0.3 ng) per ml. The level increased steadily to between 3 – 24 pmol (1 – 9 ng) per ml at about 2 days before lambing. An upsurge then followed reaching a maximal concentration between 40 – 130 pmol (15 – 50 ng) per ml. Unconjugated estrone and estradiol levels were appreciable only in the last 2–3 days of pregnancy and the profiles at this time followed closely that of estrone sulfate so that the molar ratio of estrone sulfate: estrone: estradiol remained remarkably constant at approximately 100:2:1 in spite of the great individual variations in absolute concentrations. The progesterone level was higher than that of estrone sulfate throughout pregnancy except 1–2 days prior to parturition. The sharp decline in progesterone concentration in the last two days coincided with the upsurge of estrone sulfate, but the net decrease in concentration was only about one-third of the net increase in estrone sulfate concentration during this period. These data are discussed in relation to the possible role of estrone sulfate and the possibility of placental conversion of progesterone to estrone sulfate during late pregnancy in the ewe.

STUDIES ON THE PATTERN OF CIRCULATING STEROIDS IN THE NORMAL MENSTRUAL CYCLE

ABSTRACT The plasma levels of oestrone sulphate, oestradiol sulphate, oestrone and oestradiol were studied in samples collected daily from 8 normally menstruating women throughout a complete menstrual cycle. In order to ascertain the normality of the cycles studied, LH and progesterone were also determined daily. All compounds were measured by radioimmunoassay, the sulphates after solvolysis. For the determination of the sulphates a procedure was developed which fulfilled the recognized criteria of reliability. Both oestrone sulphate and oestradiol sulphate displayed a marked cyclic pattern, similar to and correlated with that of oestrone and oestradiol, i. e., all 4 oestrogens exhibited a marked mid-cycle peak and elevated levels during the luteal phase. The mean levels of the steroid moiety of oestrone sulphate were 10–15 times higher than those of oestrone, and 2–3 times higher than those of the 3 other oestrogens together. On the other hand, the mean levels of oestradiol sulphate were 1.2 to 4 times lower than those of oestradiol. The ratios of the levels of various pairs of oestrogens were calculated. All pairs showed a considerable change of ratios from the early follicular phase to mid-cycle. This demonstrates that the mutual metabolic equilibria of oestrogens are different in various phases of the cycle. Daily measurements of oestrone sulphate and oestradiol sulphate do not seem to provide a better index to predict the day of ovulation than the characteristic changes in progesterone and 17-hydroxyprogesterone levels.

Influence of aging upon the urinary hormone excretion in the male.

The urinary excretion of LH, low polar oestrogens, neutral C19 and C21 steroids was measured in normal healthy males aged 20-79 years. No significant changes could be noted for the excretion of LH, pregnanediol and 17-ketogenic steroids between 50 and 79 years. The excretion of androsterone and aeticholanolone was significantly lower in the oldest group (70-79 years). A significant drop in the excretion of DHA was noted at approx. 60 years. The excretion of low polar oestrogens remained constant from 20 to 55-59 years, but showed a highly significant (P less than 0.001) decrease at about 60 years. This drop might reflect a sudden decrease in the plasma levels of oestrone sulphate due to a decreased sulphurylating activity in the liver.

PLASMA LEVELS OF ESTRONE SULFATE, ESTRONE AND ESTRADIOL-17β IN THE COW AROUND PARTURITION

Estrone sulfate, estrone, and estradiol-17β have been assayed in blood plasma taken from the mammary vein of five pregnant cows before and after parturition. While there were considerable individual variations, the mean plasma levels of estrone sulfate (13.4 ng/ml), estrone (1 ng/ml) and estradiol-17β (1 ng/ml) remained fairly constant over the period of blood collection prior to parturition (−88 h to −2 h). The levels of all three estrogens dropped rapidly within 8 h postpartum. It is concluded that estrone sulfate, rather than estrone, is the predominant plasma estrogen in late pregnancy in the cow.

Changes in plasma levels of estrone sulfate and estrone in the pregnant ewe around parturition

A method for the extraction, separation and measurement of estrone sulfate and estrone in a single plasma sample is described. The method has been applied to the determination of plasma levels of estrone sulfate and estrone in pregnant ewes over the period 60 hr before to 20 hr after parturition. The study revealed that the plasma levels of estrone sulfate and estrone began to increase about 40 hr before parturition, reached a peak at parturition and then declined rapidly to levels below the sensitivity of the method by 15 hr postpartum. The peak level of estrone sulfate recorded at parturition was 103 pmol (38 ng) per ml of plasma which was approximately 30 times greater than the corresponding peak level of estrone.