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At least 163 records · Page 9Linked to original sources

Methodology of the thyroid gland disease decision-making using profiling in steroid hormone pathway.

To find out the genetic factors of outbreak of thyroid gland disease, we developed the thyroid gland decision-making system, which processes the metabolic profile in steroid hormone map using a statistical method. Metabolic profile is a measured data of lots of mixed materials that includes not only known metabolites, but also unknown ones, which is estimated to have an influence on the thyroid gland disease. Therefore, to develop thyroid gland disease decision-making system, analyzing metabolic profile containing multi-materials would be useful for diagnosing thyroid gland disease. Because experimental values used for system construction are area values for the retention time, the observations are preprocessed through variable transition and t-test to use the area values concurrently and the highly correlated materials are estimated by principal component analysis. The thyroid gland decision-making system developed through the logistic regression is an excellent system demonstrating 98.7% accuracy in the classification table.

Algorithms↗

Genome-wide expression profile of steroid response in Saccharomyces cerevisiae.

The response of the yeast Saccharomyces cerevisiae to human steroid hormone progesterone was studied by genomic expression profiling. The transcription profile data revealed that steroid response was a global phenomenon wherein a host of genes were affected. For example, 163 genes were upregulated and 40 genes were downregulated, by at least more than twofold. The major categories of upregulated genes included protein destination (15%), metabolism (14%), transport facilitation (12%), cell growth, cell division, and DNA synthesis (8%), and transcription (7%), while metabolism (22%), transcription (11%), intracellular transport (10%), cell growth, cell division, and DNA synthesis (10%), energy (8%), cell rescue, defense, and cell death (6%), and protein synthesis (6%) encoding genes were downregulated. Notwithstanding the fact that yeast cells do not possess commonly occurring steroid response cascade similar to higher eukaryotes, our results demonstrate that a short-term exposure to progesterone results in differential regulation of predominantly stress responsive genes.

Gene Expression Profiling↗

Serum steroid hormone profiles in postmenopausal smokers and nonsmokers.

Morning serum steroid levels were determined in postmenopausal chronic smokers and nonsmokers. Postmenopausal smokers (n = 9) had significantly elevated levels of cortisol, progesterone (P), 17-hydroxyprogesterone (17-OHP), androstenedione, and testosterone compared with nonsmokers (n = 16). The increases were most significant for cortisol (P less than 0.001) and 17-OHP (P less than 0.0005). Estrone, estradiol, dihydrotestosterone, and dehydroepiandrosterone sulfate did not differ between the groups. P to estrogen ratios tended to be higher in the smoking population. The significantly elevated P levels observed in the group of postmenopausal smokers may explain, in part, the epidemiologic finding that women smokers have a decreased incidence of endometrial carcinoma. In addition, the hypercortisolism associated with smoking may increase the risk of osteoporosis.

17-alpha-Hydroxyprogesterone↗

Measurement of steroid hormones in plasma by isocratic high performance liquid chromatography coupled to radioimmunoassay.

The study of steroidal profiles requires simultaneous determinations of various steroid hormones that cannot be appropriately carried out with the conventional routine immunoassays. Moreover, there are several trials for which the assessment of multiple steroids from a single serum sample is mandatory. In this paper we describe a procedure for simultaneously measuring steroid hormones using a unified solid phase extraction which allows the measurement of both unconjugated and conjugated steroids from 1 ml of sample and a combination of HPLC with isocratic elution followed by RIA. The entire procedure was preliminary carried out for the measurement of testosterone, dehydroepiandrosterone and its sulphated conjugate, androstenedione and 17 hydroxyprogesterone. The use of this technique allows precise and accurate measurements of steroid profile with a single serum aliquot and could be helpful in the diagnosis of various form of endocrine disorders.

Animals↗

Reversed-phase liquid chromatographic separation and simultaneous profiling of steroidal glycoalkaloids and their aglycones.

Improved and simplified reversed-phase liquid chromatographic conditions for the separation and simultaneous profiling of both steroidal glycoalkaloids and their aglycones, having solanidane- or spirosolane-type structures, are described. The most reproducible retention behavior for these ionizable compounds on C18 columns was achieved under isocratic and gradient elution conditions using acetonitrile in combination with triethylammonium phosphate buffer at pH 3.0, when basic functional groups of solutes and silanol groups on the silica are fully protonated minimizing ionic interactions. Gradient elution was the only feasible approach for the simultaneous separation of steroidal glycoalkaloids and their aglycones. A Zorbax SB C18 column, specially designed for low-pH separations, showed good performance in critical separations. The impurities of the commercial tomatine and tomatidine standards were studied and confirmed using mass spectrometric, liquid chromatographic and thin-layer chromatographic methods.

Alkaloids↗

The effect of ICI 164384 and beta-interferon on the growth and steroid receptor profile of breast cancer cell lines.

We investigated the effect of a concomitant treatment of ICI 164384 and B-interferon (beta-IFN) on the growth of estrogen-receptor-positive (ER+) and estrogen-receptor-negative (ER-) breast cancer cell lines and on their steroid receptor profiles. ICI 164384 reduced cell proliferation not only in ER+ but also in ER- cell lines and completely suppressed the stimulation induced by estradiol (E2) in hormone-sensitive cell lines, MCF7 and T47D. When associated with beta-IFN, ICI 164384 increased the inhibitory effect exerted by the low concentration of beta-IFN. Moreover, ICI 164384, singly or in association with beta-IFN, did not affect ER and PgR concentration in ER- cell lines, whereas in ER+ cell lines we observed an almost total disappearance of ER and PgR. In conclusion, our study seems to indicate that, although beta-IFN is able to control the proliferation of hormone-sensitive and hormone-independent subclones, it does not further improve the antiproliferative activity of ICI 164384. In contrast, the presence of ICI 164384, which does not induce the selection of resistant subclones under the same experimental conditions in which TAM does, may improve the efficacy of low concentration of beta-IFN and prevent the development of a secondary TAM-induced resistance.

Adenocarcinoma↗

[The effect of subclinical and acute ante partum acidosis in cows on the course of pregnancy with regard to the steroid hormone profile].

Experiment 1: In a field experiment in 19 of 87 cows being in day 260-265 of pregnancy subclinical metabolic acidosis was found. The control group included 10 healthy cows in the same stage of pregnancy. Blood samples from cows of both groups were collected once daily until day 2 post partum for determination of oestrogens, progesterone and cortisol. Dystocia was found in four and retained placenta in three cows having acidosis. These cows had lower oestrogens and markedly higher cortisol and progesterone concentrations during parturition. Course of pregnancy and delivery in control cows an without any difficulties and hormonal profiles in these cows were typical. Experiment 2: On day 265 of pregnancy experimental acute acidosis was evoked in five cows and five other cows served as control. Sampling of blood was the same as in experiment 1. Acidosis caused on day 269 in two cows premature birth with retained placenta. Moreover concentrations of studied steroids were atypical. In three other cows with acidosis course of pregnancy and delivery was without any trouble. Only cortisol was increased while progesterone and oestrogen values were in agreement with concentrations of control cows. Data suggest that metabolic acidosis can cause dystocia, premature birth and retained placenta. Furthermore, acidosis clearly affects the profile of steroid hormones.

Acid-Base Equilibrium↗

Steroid hormone profile in postmenopausal women with ovarian cancer.

Raised levels of steroid hormones are not expected in postmenopausal women. Therefore, if detected in postmenopausal women with ovarian cancer, they must be assumed to be related to the presence of the tumour and, therefore, may be of use as tumour markers. Serum levels of CA125, progesterone, 17-hydroxyprogesterone, sex hormone binding globulin and oestradiol were measured in 44 postmenopausal women with ovarian cancer, postsurgery and prior to chemotherapy. The relationship between the four hormone levels, CA125, patient age, stage, residual disease after surgery and differentiation were tested using the Spearman and Kendall rank coefficients. A significant inverse association was found between CA125 and progesterone levels, and CA125 and 17-hydroxyprogesterone. A positive association between 17-hydroxyprogesterone and progesterone was also found, and positive correlations between stage and CA125, and residual disease and CA125 were confirmed.

17-alpha-Hydroxyprogesterone↗

Determination of steroidal hormone profiles along the Jalle d'Eysines River (near Bordeaux, France).

Steroidal estrogens have been shown to be the main contributors to the estrogenic activity observed in aquatic systems contaminated with sewage treatment work effluents. Although the occurrence of steroid hormones in the environment has received a great deal of attention, little is known about their fate in aquatic systems. In the presentwork, concentrations of conjugated and unconjugated hormonal steroids (estrone, 17beta-estradiol, estriol, 17alpha-ethynylestradiol, mestranol, progesterone, norethindrone, and D-norgestrel) were determined in the effluent of the Eysines sewage treatment plant (near Bordeaux, France), and along the receiving river, the Jalle d'Eysines River. Sampling was undertaken in summer and in winter conditions, to study both the temporal and the spatial distributions of steroids in this river. Only unconjugated natural estrogens were detected in the effluent. Estrone was the dominant compound (detected in all effluent samples, 17.1-71.0 ng x L(-1)), while estradiol and its metabolite estriol were detected only once, at much lower levels (4.4 and 2.9 ng x L(-1), respectively). Levels of estrogens were clearly raised above the detection limits downstream of the Eysines STP effluent discharge. Seasonal variations of estrone degradation rates were observed. In summer, the apparent decay rates of estrogen levels exceeded that of dilution, indicating high removal rates from the water column: 50% of the initial amount of this steroid was degraded within 1.7 km downstream of the effluent discharge. In winter, however, estrone levels did not significantly decrease over a 10 km reach downstream of the effluent discharge (1.9-1.8 ng x L(-1)). Steroids were determined in the particulate material of the river, but levels were below the detection limits (0.4-1.9 ng x g(-1)), indicating that sorption was not a major sink of estrogens. Therefore, it is likely that biodegradation plays a major role in the removal of steroids from the river and the different decay rates are probably related to differences in bacterial activity within the river.

Environmental Monitoring↗

Polycystic ovarian disease: diagnosis, frequency and symptoms in a general gynaecological practice.

A study was undertaken to assess the relative frequency of polycystic ovarian disease (POD) among patients with menstrual irregularities and/or hirsutism, and was based on 24-hour urinary steroid profiles under basal conditions, after dexamethasone suppression and after human chorionic gonadotrophin (HCG) stimulation. The final diagnosis was confirmed by laparoscopy or laparotomy and ovarian histology. Fifty-six patients were studied, 38 (38 per cent) of whom had POD. Laboratory results were subjected to multivariate discriminant analysis and a discriminant function was calculated to classify patients into POD, and non-POD subgroups. Steroid profiling under basal conditions was sufficient to classify most of the patient into one of three groups: normal, POD and other endocrinopathies. Of the patients with POD, 70 per cent had an abnormal reaction to dexamethasone or HCG. Significant differences were found in the steroid profiles of ovulating and non ovulating patients with POD.

Adult↗

Is steroid receptor profile in contralateral breast cancer a marker of independence of the corresponding primary tumour?

We compared oestrogen receptor (ER) and progesterone receptor (PgR) profiles between primary and corresponding contralateral breast cancer (CBC) to investigate whether CBC should be considered relapse of a primary or as a feature of the multicentric origin of breast cancer. We adjusted for patient age, menopausal status, histology and adjuvant therapy. In spite of the general application of a cut-off value to dichotomise ER and PgR, we considered them as continuous variables. Moreover, we considered as synchronous cancers only simultaneously occurring lesions. For 399 patients, ER and PgR receptor levels in primary and CBC did not differ significantly, but were significantly correlated within the same patient. The correlation was higher for synchronous than for metachronous lesions when considering ER, but not PgR. The correlation between ER and PgR levels in the same tumour (primary or CBC) appeared stronger than the correlation of either receptor type (ER or PgR) between primary and CBC. Age, histology and adjuvant treatment affected ER concentration, whereas age, menopausal status and histology affected PgR concentration. The analysis indicated that primary and CBC tend to be characterised by a similar steroid receptor profile. The finding may support the hypothesis of CBC as a second primary arising in a common predisposing milieu, rather than a primary-dependent contralateral lesion. In this light, the clinical management of patients with a bilateral breast cancer should be similar to that of a unilateral breast cancer.

Adult↗

Menstrual disturbance and hypersecretion of progesterone in women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

OBJECTIVE: While menstrual disturbance is often quoted as a feature of congenital adrenal hyperplasia (CAH), little is known about the mechanism of this symptom. We set out to determine the relationship between menstrual pattern and biochemical characteristics of women with CAH due to 21-hydroxylase deficiency. PATIENTS AND DESIGN: All 21 female patients with classic CAH attending the adult endocrinology clinics at The Middlesex Hospital were reviewed. Their ages at menarche and menstrual pattern were recorded and blood samples were taken in the follicular phase of the menstrual cycle when on their usual maintenance therapy. MEASUREMENTS: Measurements of serum LH, FSH, progesterone, 17 alpha-hydroxyprogesterone, testosterone, androstenedione and plasma renin activity were recorded. Urinary steroid profiles were obtained by gas chromatography and mass spectrometry. Molecular genetic analysis of the 21-hydroxylase gene was performed on leucocyte DNA. RESULTS: In the 18 patients who had spontaneous menarche the degree of menstrual disturbance and progesterone excess was related to the effectiveness of adrenal suppressive therapy. Three out of 21 patients, however, failed to experience menarche on standard medical therapy. These patients with primary amenorrhoea were characterized by reduced endometrial thickening, by non-suppressible serum progesterone concentrations despite suppression of 17 alpha-hydroxyprogesterone levels and by the presence of progesterone metabolites in urinary steroid profiles. Molecular genetic analysis did not differentiate between patients with raised progesterone concentrations and those without. CONCLUSION: A subgroup of women with congenital adrenal hyperplasia have the triad of non-suppressible serum progesterone of adrenal origin, primary amenorrhoea and infertility due to failure of endometrial thickening. The characteristic urinary steroid profile best distinguishes this subgroup of women from others with congenital adrenal hyperplasia and menstrual disturbance due to inadequate adrenal suppression.

17-alpha-Hydroxyprogesterone↗

Basal and estradiol-induced release of gonadotropins in dairy cows with naturally occurring ovarian cysts.

A study was conducted to identify relationships between serum sex steroid concentrations and release of gonadotropins in dairy cows with ovarian cysts. Cows with ovarian cysts were grouped according to sex steroid profiles as being under estrogenic (n = 6) or low steroid (n = 6) influence. All cows were submitted to a sampling and treatment protocol to 1) record basal pulsatile release of gonadotropins and 2) determine whether luteinizing hormone (LH) or follicle stimulating hormone (FSH) was released after sequential administration of exogenous estradiol and gonadotropin releasing hormone (GnRH) treatments were given 30 h apart. Basal LH was higher in the estrogen-influence group (P < 0.05). There were no differences between groups in basal FSH concentrations or frequency and amplitude of pulsatile LH or FSH release. Only one of the twelve cows, an individual from the low steroid group, had a preovulatory-like surge of gonadotropins after exogenous estradiol. All cows released LH and FSH in response to GnRH treatment, with no differences between groups. These results show that 1) there is considerable variation in pulsatile release of gonadotropins in cows with ovarian cysts, even among individuals with similar sex steroid profiles, and 2) suggest that a factor in the persistence, and perhaps initiation, of the cystic condition is refractoriness to the positive feedback effect of estradiol on gonadotropin release.

Journal Article↗

Influence of oral dehydroepiandrosterone (DHEA) on urinary steroid metabolites in males and females.

Oral dehydroepiandrosterone (DHEA) replacement therapy may have a multitude of potential beneficial effects and exerts its action mainly via peripheral bioconversion to androgens (and estrogens). A daily dose of 50-mg DHEA has been shown by us and others to restore low endogenous serum DHEA concentrations to normal youthful levels followed by an increase in circulating androgens and estrogens. As the hepatic first-pass effect may lead to a non physiological metabolism of DHEA after oral ingestion we studied the influence of two single DHEA doses (50 and 100 mg) on the excretion of steroid metabolites in 14 elderly males [age 58.8+/-5.1 years (mean +/- SEM)] with endogenous DHEAS levels <1500 ng/ml and in 9 healthy females (age 23.3+/-4.1 years) with transient suppression of endogenous DHEA secretion induced by dexamethasone (dex) pretreatment (4x0.5 mg/day/4 days). Urinary steroid profiles in the elderly males were compared to the steroid patterns found in 15 healthy young men (age 28.9+/-5.1 years). In the females the results were compared to their individual baseline excretion without dex pretreatment. Urinary steroid determinations were carried out by semiautomatic capillary gas-liquid chromatography. In both genders DHEA administration induced significant increases in urinary DHEA (females: baseline vs. 50 mg vs. 100 mg: 361+/-131 vs. 510+/-264 vs. 1541+/-587 microg/day; males: placebo vs. 50 mg vs. 100 mg: 434+/-154 vs. 1174+/-309 vs. 4751+/-1059 microg/day) as well as in the major DHEA metabolites androsterone (A) and etiocholanolone (Et). Fifty mg DHEA led to an excretion of DHEA and its metabolites only slightly above baseline levels found in young females and in young men, respectively, whereas 100 mg induced clearly supraphysiological values. After 50 mg DHEA the ratios of urinary DHEA metabolites (A/DHEA, Et/DHEA) were not significantly different between elderly males vs. young male volunteers and young healthy females versus their individual baseline levels. In conclusion, an oral dose of 30 to 50 mg DHEA restores a physiological urinary steroid profile in subjects with DHEA deficiency without evidence for a relevant hepatic first-pass effect on urinary metabolites.

Administration, Oral↗

Inadequate cervical mucus--a cause of "idiopathic" infertility.

The purpose of this study was to investigate and treat a group of patients referred for "idiopathic" infertility in whom no apparent cause for infertility, apart from inadequate cervical mucus, was found. Hormone investigations revealed that these patients could be divided into two groups: those with low sex steroid profiles despite apparent ovulation, and a second group with normal sex steroid profiles. All patients were treated with ovulation-inducing agents in an attempt to produce "controlled" ovarian hyperstimulation and an improved cervical mucus. Four of six patients conceived. The rationale behind the use of ovulation-inducing agents in this situation is discussed.

Adult↗

Treatment of hormone-producing adrenocortical cancer with o,p'DDD and streptozocin.

Three patients with advanced adrenocortical carcinoma were treated with a combination of intermittent streptozocin and continuous o,p'DDD. Two patients were treated preoperatively and the primary tumors, initially considered as inoperable, could be resected after 19 and 5.5 months, respectively. In the patient with the longer treatment (35 months), lung and lymph node metastases disappeared and she has no evidence of recurrent disease 6.5 years after start of therapy. One patient was followed by magnetic resonance imaging (MRI) and urinary steroid secretion. The MRI gave a good visualization of the tumor. Measurements of relaxation times showed a significant decrease in T1 values. The urinary steroid profile showed an increased secretion of 3 beta-hydroxy-5-ene steroids and tetrahydro-11-deoxy-cortisol. Treatment with streptozocin and o,p'DDD initially increased 16-oxygenation of dehydroepiandrosterone and androst-5-en-3 beta,17 beta-diol, followed by a decrease in the secretion of all urinary steroids. The third patient received postoperative treatment with no effect on metastatic disease in the lungs, she died 9 months after start of treatment. The therapeutic approach with the combination regimen of streptozocin and o,p'DDD pretreatment plus aggressive surgery has to be further evaluated, as well as MRI and urinary steroid profile as methods to monitor the effect of therapy.

Adrenal Cortex↗

Simultaneous determination of 12 steroids by isotope dilution liquid chromatography-photospray ionization tandem mass spectrometry.

BACKGROUND: Serum steroid assays play an important role in the clinical evaluation of a number of common endocrine disorders. Among various assays, tandem mass spectrometry (MS/MS) has being increasingly applied in clinical laboratories for its high sensitivity, specificity, and simultaneous multi-analyte quantitation capability. Our first generation isotope dilution steroid profile assay by HPLC-tandem MS/MS with a C-18 column allowed for the measurement of 9 steroids in 18 min employing a sample volume of 760 ul serum. We describe our second generation steroid profile assay which allows for the quantitation of 12 steroids simultaneously employing HPLC-MS/MS and isotope dilution tandem MS in 11 min. This method requires a sample volume of 200 microl. METHODS: An API-5000 triple-quadrupole mass spectrometer (Sciex, Concord, Canada) coupled with the PhotoSpray source and Shimadzu HPLC system (Shimadzu Scientific Instruments, Columbia, MD) was used employing isotope dilution with deuterium labeled internal standard (IS) for each analyte. Two hundred microliters of serum were deproteinized by adding 300 microl of acetonitrile containing internal standards. After centrifugation, 450 microl of supernatant were diluted with 900 microl of water and 1000 microl aliquot were injected onto a C-8 column. After a 3 min wash the valve was activated to initiate the gradient elution program which eluted the steroids. Quantitation by MRM analysis was performed both in positive ion mode for 11 analytes and in negative ion mode for aldosterone. Within-day and between-day precision, reliability and accuracy of this method were assessed by correlation with other MS/MS and immunoassay methods and by recovery study. RESULTS: Within-day CVs were <11.5% for all analytes tested and between-day CVs ranged from 3.5% to 12.2%. The results of the comparison study yield r values ranging between 0.908 and 0.999. Recovery ranged from 90% to 110%. CONCLUSIONS: This method can simultaneously measure 12 steroids in serum within 11 min with minimal sample preparation. It can be routinely employed in a clinical environment and is attractive because of its simplicity in sample processing and high throughput.

Chromatography, High Pressure Liquid↗

Adrenarche is dissociated from gonadarche--studies in patients with Turner's syndrome.

Twenty-two patients with gonadal dysgenesis (14 45,XO; median age 13.6 years; 8 mosaics, median age 12.3 years) were studied regarding their clinical onset of adrenarche (pubarche) and breast development. The latter was considered evidence of gonadarche. 1/22 showed breast development, stage 2; 9/22 had pubarche, stage 2-4. The 24h-urinary excretion of androsterone, etiocholanolone, dehydroepiandrosterone, 16 alpha- and 16 beta-dehydroepiandrosterone was studied in these patients by urinary capillary column gas chromatography profiling. The urinary steroid profiles of twenty-one healthy, normal girls (median age 10.4 years) served as controls. Dehydroepiandrosterone and its 16-hydroxylated derivatives were excreted in significantly greater amounts by the patients with Turner's syndrome as compared to normal girls. These findings support the hypothesis, that adrenarche is independent of gonadarche and proceeds even in instances of gonadal dysgenesis.

Adolescent↗