Design, synthesis and anticancer activity of 5-((2-(4-bromo/chloro benzoyl) benzofuran-5-yl) methyl)-2-((1-(substituted)-1H-1,2,3-triazol-4-yl)methoxy)benzaldehyde analogues.

Novel 5-((2-(4-bromo/chloro benzoyl) benzofuran-5-yl) methyl)-2-((1-(substituted)-1H-1,2,3-triazol-4-yl)methoxy)benzaldehyde analogues about twenty-one were synthesized all through standard chemical procedures. The structure of the compounds were confirmed by 1H NMR, 13C NMR and Mass spectral analysis after purification. All the compounds were screened for In Vitro lung and cervical cancer activity against A-549 and HeLa cell lines, respectively, by MTT assay protocol using various nanomolar (nM) concentrations. IC50 value were calculated from cell viability data. 2-(trifluoromethyl)benzyl substituted derivative presented outstanding activity against both the cell lines compared to standard drug doxorubicin. The methoxy, chloro, fluoro and formyl substituted analogues showed a moderate activity and whereas methyl substituted analogues activity was poor. The morphological deformation of both cell lines by best IC50 value analogues proved as potent inhibitors of cancer cells growth. Molecular docking studies were performed against extracellular signal-regulated kinase 2 and fibroblast growth factor receptor 2 these results are incredibly in agreement with the investigational data.

Development of artificial neural networks software for arsenic adsorption from an aqueous environment.

Arsenic contamination is a global problem, as it affects the health of millions of people. For this study, data-driven artificial neural network (ANN) software was developed to predict and validate the removal of As(V) from an aqueous solution using graphene oxide (GO) under various experimental conditions. A reliable model for wastewater treatment is essential in order to predict its overall performance and to provide an idea of how to control its operation. This model considered the adsorption process parameters (initial concentration, adsorbent dosage, pH, and residence time) as the input variables and arsenic removal as the only output. The ANN model predicted the adsorption efficiency with high accuracy for both training and testing datasets, when compared with the available response surface methodology (RSM) model. Based on the best model synaptic weights, user-friendly ANN software was created to predict and analyze arsenic removal as a function of adsorption process parameters. We developed various graphical user interfaces (GUI) for easy use of the developed model. Thus, a researcher can efficiently operate the software without an understanding of programming or artificial neural networks. Sensitivity analysis and quantitative estimation were carried out to study the function of adsorption process parameter variables on As(V) removal efficiency, using the GUI of the model. The model prediction shows that the adsorbent dosages, initial concentration, and pH are the most influential parameters. The efficiency was increased as the adsorbent dosages increased, decreasing with initial concentration and pH. The result show that the pH 2.0-5.0 is optimal for adsorbent efficiency (%).

Chemical characteristics of groundwater and assessment of groundwater quality in Varaha River Basin, Visakhapatnam District, Andhra Pradesh, India.

Study on chemical characteristics of groundwater and impacts of groundwater quality on human health, plant growth, and industrial sector is essential to control and improve the water quality in every part of the country. The area of the Varaha River Basin is chosen for the present study, where the Precambrian Eastern Ghats underlain the Recent sediments. Groundwater quality is of mostly brackish and very hard, caused by the sources of geogenic, anthropogenic, and marine origin. The resulting groundwater is characterized by Na(+) > Mg(2+) > Ca(2+) : [Formula: see text] > Cl(-) > [Formula: see text], Na(+) > Mg(2+) > Ca(2+) : [Formula: see text] > Cl(-) > [Formula: see text] > [Formula: see text], Na(+) > Mg(2+) > Ca(2+) : [Formula: see text] > Cl(-), and Na(+) > Mg(2+) > Ca(2+) : Cl(-) > [Formula: see text] > [Formula: see text] facies, following the topographical and water flow-path conditions. The genetic geochemical evolution of groundwater ([Formula: see text] and Cl(-)-[Formula: see text] types under major group of [Formula: see text]) and the hydrogeochemical signatures (Na(+)/Cl(-), >1 and [Formula: see text]/Cl(-), <1) indicate that the groundwater is of originally fresh quality, but is subsequently modified to brackish by the influences of anthropogenic and marine sources, which also supported by the statistical analysis. The concentrations of total dissolved solids (TDS), TH, Mg(2+), Na(+), K(+), [Formula: see text], Cl(-), [Formula: see text], and F(-) are above the recommended limits prescribed for drinking water in many locations. The quality of groundwater is of mostly moderate in comparison with the salinity hazard versus sodium hazard, the total salt concentration versus percent sodium, the residual sodium carbonate, and the magnesium hazard, but is of mostly suitable with respect to the permeability index for irrigation. The higher concentrations of TDS, TH, [Formula: see text], Cl(-), and [Formula: see text] in the groundwater cause the undesirable effects of incrustation and corrosion in many locations. Appropriate management measures are, therefore, suggested to improve the groundwater quality.

Toward gene therapy of primary ovarian failure: adenovirus expressing human FSH receptor corrects the Finnish C566T mutation.

Resistance ovarian syndrome is a heterogeneous disorder inherited as a Mendelian recessive trait and characterized by infertility, primary amenorrhea, normal karyotype and elevated serum FSH and LH levels. An inactivating mutation, C566T, in FSH receptor gene (FSHR) has been identified initially in Finland. We investigated if an adenovirus expressing a normal copy of human FSHR (Ad-hFSHR) has the ability to: (i) transfect granulosa cell lines, (ii) render the transfected cell lines responsive to FSH stimulation and (iii) transcomplement the malfunctioning form of human FSHR gene with C566T mutation. COS-7, JC-410, JC-410-P450-scc-luc and JC-410-StAR-luc cell lines were infected by Ad-hFSHR followed by treatment with FSH. Functional activity of the Ad-hFSHR was tested by measuring cyclic adenosine monophosphate (cAMP) or luciferase activity in response to FSH stimulation, and showed 2-4.6-fold increases in Ad-hFSHR transfected cells compared with untransfected or Ad-LacZ transfected cells, indicating that Ad-hFSHR is functionally active and expressing hFSHR. Generation of cAMP in cells expressing only mutated hFSHR-T566 showed minimal increase after FSH stimulation. Co-transfection of Ad-hFSHR in these cells carrying the malfunction form of human FSHR caused significant increases of 2.2-7.4-fold in FSH dependent cAMP generation (P = 0.0007). We concluded that adenovirus expressing a normal human FSHR can compensate the inactivating human FSHR-C566T mutation and restore FSH responsiveness.

Increased urinary excretion of 2-hydroxyestrone but not 16alpha-hydroxyestrone in premenopausal women during a soya diet containing isoflavones.

Asian diets high in soy are associated with lower risk for breast cancer compared with Western diets. Moreover, higher levels of two putative carcinogenic metabolites of 17beta-estradiol, 4- and 16alpha-hydroxyestrogen, and lower amounts of anticarcinogenic metabolites, 2-hydroxyestrogens, have been associated with greater breast cancer risk. In this study, we tested the hypothesis that consumption of a soya diet containing the weakly estrogenic isoflavones genistein and daidzein may alter the metabolism of 17beta-estradiol to 2- and 16alpha-hydroxylated products. Eight pre-menopausal women were placed on a soya-containing, constant diet in a metabolic unit. The diet provided 400 kilocalories from soymilk and 113-202 mg/day (158 +/- 26 mg/day, mean +/- SD) isoflavones daily for a complete menstrual cycle. After a washout period of 4 months, the subjects consumed the same diet, but with soymilk that contained <4.5 mg/day isoflavones ("isoflavone-free"). Urine samples were collected for 24 h daily for the entire cycle during each soya diet period for the analysis of daidzein, genistein, and 2- and 16alpha-hydroxyestrone. Subjects excreted measurable amounts of daidzein (11.6-39.2 mg/day) and genistein (2.9-18.2 mg/day) during the isoflavone-rich soya diet but not during the isoflavone-free soya diet. The diet rich in isoflavones increased the cycle mean daily urinary excretion of 2-hydroxyestrone (averaged over the entire cycle) from 11.6 +/- 2.06 to 17.0 +/- 2.96 nmol/12-h (P = 0.03), a 47% increase. However, the mean daily excretion of 16alpha-hydroxyestrone did not change (7.0 +/- 1.14 nmol/12-h during the isoflavone-free and 7.7 +/- 1.25 nmol/12-h during the isoflavone-rich diet; P = 0.36). The ratio of 2-hydroxyestrone to 16alpha-hydroxyestrone was higher during the isoflavone-rich soya diet (2.6 +/- 0.34) than during the isoflavone-free diet (2.0 +/- 0.32; P = 0.01), a 27% increase. These results suggest that soya isoflavones increase the metabolism of endogenous estrogens to the protective 2-hydroxylated estrogens in women, and this may play an important role in lowering 17beta-estradiol levels and the long-term risk for breast cancer.

Decreased ovarian hormones during a soya diet: implications for breast cancer prevention.

Ovarian hormones are biomarkers for breast cancer risk. Soybean consumption may be responsible in part for lower levels of ovarian hormones and decreased rates of breast cancer in women in Asia compared with Western populations. Soybeans contain a significant amount of the isoflavones daidzein and genistein, which are weak estrogens. The purpose of this study was to determine whether soya feeding decreases circulating levels of ovarian hormones and gonadotropins. Ten healthy, regularly cycling women consumed a constant soya-containing diet on a metabolic unit, starting on day 2 of a menstrual cycle until day 2 of the next cycle. Blood and urine samples were obtained daily for one menstrual cycle before and during soy feeding. The diet was calculated to maintain constant body weight, included 400 kilocalories from a 36-ounce portion of soymilk, and provided 113-207 mg/day (154.0+/-8.4 mg/day, mean +/- SE) of total isoflavones. For the group, the soya diet provided more carbohydrate and less protein than the home diets. Daily consumption of the soya diet reduced circulating levels of 17beta-estradiol by 25% (P<0.01, Wilcoxon signed rank test, two-tailed) and of progesterone by 45% (P<0.0001) compared with levels during the home diet period but had no effect on luteinizing hormone or follicle-stimulating hormone. Mean menstrual cycle length did not change during the soya diet; a slight decrease in mean luteal cycle length was marginally statistically significant (P = 0.06). Urinary excretion of isoflavones was 33.8+/-5.3 mg/day (mean +/- SE) and when expressed as percentage of intake, varied substantially (21.9+/-3.3% of intake; range, 9.1-36.7%) among the subjects. Mean daily serum levels of daidzein and genistein (free and conjugated forms) 15 h after soymilk were 2.89+/-0.53 microg/ml and 0.85+/-0.22 microg/ml, respectively, indicating systemic bioavailability of these substances. Secondary analyses by multiple regression showed that decreases in follicular and luteal phase 17beta-estradiol levels were positively associated with urinary isoflavone excretion, an association affected by age, and were inversely associated with decreases in protein intake. Decreases in progesterone levels during the soya diet were inversely associated with increases in intakes of genistein and were affected by the interaction of the intakes of daidzein with energy or with fiber. Consumption of an isoflavone-containing soya diet reduced levels of ovarian steroids in normal women over the entire menstrual cycle without affecting gonadotropins. This suggests that at least under the conditions of this study, soya-induced reductions of circulating ovarian steroids are not mediated by gonadotropins. Decreases in ovarian hormones are related to isoflavones contained in soy and also to energy intake and other components such as protein and fiber but not fat. Our results may explain decreased ovarian hormone levels and decreased risk of breast cancer in populations consuming soya diets and have implications for reducing breast cancer risk by dietary intervention.

Troglitazone inhibits progesterone production in porcine granulosa cells.

Troglitazone (a thiazolidinedione that improves insulin resistance) lowers elevated androgen concentrations in women with polycystic ovarian syndrome. In this study, we assessed the direct effects of troglitazone on steroidogenesis in porcine granulosa cells. Troglitazone inhibited progesterone production in a dose- and time-dependent manner (earliest effects at 4 h, maximum at 24 h) without affecting cell viability. Progesterone production was also inhibited by troglitazone in the presence of 25-hydroxycholesterol, indicating that the drug does not affect intracellular cholesterol transport. Troglitazone also inhibited FSH- and forskolin-stimulated progesterone secretion. The reduced progesterone production was accompanied by marked elevations of pregnenolone concentrations, suggesting inhibition of 3beta-hydroxysteroid dehydrogenase (3beta-HSD). The activity of 3beta-HSD in troglitazone-treated granulosa cells was decreased by more than 60%, compared with controls after 24 h. Troglitazone did not affect aromatase activity in porcine granulosa cells. In summary, troglitazone has direct effects on porcine granulosa cell steroidogenesis. The drug specifically inhibits 3beta-HSD activity, resulting in impaired progesterone production. The clinical relevance of this direct in vitro effect on steroidogenesis needs further investigation.

Increased bioactive luteinizing hormone levels and bio/immuno ratio in women with hyperthecosis of the ovaries: possible role of hyperinsulinemia.

Unlike women with polycystic ovarian disease, women with hyperthecosis have normal or low immunoactive LH levels. They have severe insulin resistance with marked hyperinsulinemia. Bioactive LH levels have not been studied in these women. The purpose of this study was to investigate 1) whether there is an increase in bioactive LH levels in women with hyperthecosis of the ovaries and 2) whether hyperinsulinemia has an effect on LH secretion. Six women with hyperthecosis of the ovaries confirmed by histological examination were included in the study. Six normal women in the midproliferative phase of the cycle served as controls. All women were admitted to the Clinical Research Center at 0800 h, and blood samples were obtained every 15 min for 6 h. All samples were assayed for LH by RIA and bioassay. The PC Pulsar Program was used for pulse analysis of LH secretion. Patients with hyperthecosis had significantly higher (P < 0.002) bioactive LH levels (66.9 +/- 13 mIU/mL) than controls (29.3 +/- 6 mIU/mL). Immunoactive LH levels in hyperthecosis were not significantly different from those in control women. Significantly higher bio/immuno LH ratios (P < 0.001) were observed in women with hyperthecosis (6.2 +/- 0.9) than in normal control women (2.4 +/- 0.5). There was a significant positive correlation between insulin levels and the bio/immuno ratio of LH. Pulse amplitude and interpulse intervals for immunoactive LH in hyperthecosis patients were similar to those in control women. The pulse amplitude of bioactive LH was significantly higher (P < 0.01) in women with hyperthecosis compared to that in normal controls. Hyperinsulinemia induced during LH sampling resulted in increased bioactive LH levels with no change in immunoactive LH. These results indicate that 1) women with hyperthecosis of the ovaries have increased secretion of biologically active LH, and 2) hyperinsulinemia may enhance the secretion of the biologically active form of LH.

Increased steroid production by the ovarian stromal tissue of postmenopausal women with endometrial cancer.

An increase in ovarian steroid secretion could play a role in the pathogenesis of endometrial cancer in postmenopausal women. The present study was undertaken to investigate steroid production by isolated ovarian stromal tissues of postmenopausal women with endometrial cancer and to study the effect of LH and insulin on ovarian steroidogenesis in postmenopausal women. Ovarian stromal tissue was obtained from 10 postmenopausal women with endometrial cancer and 8 women without cancer. The stroma was incubated in either the medium alone or the medium to which was added LH (50 ng/mL) or insulin (500 ng/mL). The ovarian stroma of postmenopausal women with cancer released significantly more androstenedione (A), testosterone, and dehydroepiandrosterone than that of women without cancer. Addition of LH resulted in a significant increase in A, testosterone, dehydroepiandrosterone, and progesterone release compared to that with vehicle alone. Addition of insulin stimulated the release of A from the ovarian stroma of women with cancer, but had no effect on the normal postmenopausal ovarian stroma. These results indicate that the ovarian stroma of postmenopausal women with endometrial cancer secrete significantly greater amounts of androgens than those of women without cancer and that both LH and insulin may be important factors contributing to this increase in ovarian steroidogenesis.

Ovarian steroid secretion in postmenopausal women with and without endometrial cancer.

The concentrations of testosterone (T), androstenedione (A), estradiol (E2), and estrone (E1) were measured in peripheral and ovarian venous serum obtained at the time of bilateral oophorectomy from 15 postmenopausal women with endometrial cancer and 9 without cancer. The cancer and noncancer (control) patients were matched for age, weight, and years since menopause. In women with endometrial cancer, significantly higher ovarian than peripheral venous concentrations were found for all hormones measured [T, 3781 +/- 1255 (+/- SE) vs. 213 +/- 43 pg/ml (P less than 0.01); A, 5352 +/- 1845 vs. 1299 +/- 187 pg/ml (P less than 0.04); E2, 52 +/- 11 vs. 23 +/- 3 pg/ml (P less than 0.02); E1, 81 +/- 12 vs. 32 +/- 2 pg/ml (P less than 0.001)], but in the control patients, only the concentration of T was significantly higher (623 +/- 108 vs. 156 +/- 21 pg/ml; P less than 0.001). Ovarian venous concentrations of T and A were significantly higher in thin women with cancer than in obese women with cancer. These results suggest that the ovaries of postmenopausal women with endometrial cancer secrete significantly more T and A than do the ovaries of women without cancer, while secreting only minimal amounts of E2 and E1. This increase in ovarian steroid secretion might play a role in the pathogenesis of endometrial cancer.

Effects of an isoflavone-free soy diet on ovarian hormones in premenopausal women.

Soy intakes have been associated with reduced rates of breast cancer in some Asian populations. The isoflavones daidzein and genistein and other components of soybeans may modulate endocrine function and lead to beneficial health effects. This study determined the effects of a soy diet containing minimum amounts of isoflavones on circulating levels of ovarian hormones and gonadotropins. Nine healthy, regularly cycling women consumed a constant soya-containing diet on a metabolic unit starting on day 2 of a menstrual cycle until day 2 of the next cycle. The soy diet was calculated to maintain constant body weight and included a 36-oz portion of soymilk that provided 334 kilocalories and less than 5 mg/day of total isoflavones. The energy distribution of the soy diet was 35.9% fat, 14.0% protein, and 49.8% carbohydrate whereas the home diets averaged 39% fat, 16.6% protein, and 42.5% carbohydrate. For the group, the soya diet provided more carbohydrate (P = 0.002) and less protein (P = 0.005) than the home diets. Daily consumption of the soya diet reduced daily circulating levels of 17beta-estradiol over the entire menstrual cycle by 20% (P < 0.01, paired t test, two-tailed) and progesterone by 33% (P < 0.0001) compared with levels during the home diet period, but had no effect on LH, FSH, or sex hormone-binding globulin. The decreases in follicular phase 17beta-estradiol during the soy diet can be accounted for by changes in energy intakes, nutrient density, and fiber intake, whereas changes in luteal phase 17beta-estradiol were most strongly associated with differences in fiber intake. Changes in progesterone levels were most strongly associated with changes in protein intake and much less with other nutrients. Isoflavones were not detectable in plasma and urine during either the soy or home diet periods. These results suggest that at least under the conditions of this study, a soy diet with low levels of isoflavones and low energy intake from protein can reduce circulating ovarian steroids without altering gonadotropins. Our results are consistent with previous studies showing decreased ovarian hormone levels and decreased risk of breast cancer in populations consuming soya diets and an inverse relationship between animal protein intake and breast cancer risk and, therefore, may have implications for breast cancer prevention.

Hyperinsulinemia and stromal luteinization of the ovaries in postmenopausal women with endometrial cancer.

Ovarian secretion of testosterone and androstenedione is increased in postmenopausal women with endometrial cancer, and insulin stimulates ovarian stromal androgen synthesis in vitro. We undertook this study to investigate whether women with endometrial cancer have increased serum immunoreactive insulin levels. Ten postmenopausal women with endometrial carcinoma and 10 postmenopausal women without cancer who matched the cancer patients in age, years since menopause, and percentage of ideal body weight were studied. The women with endometrial cancer had significantly higher fasting serum insulin levels than the normal women [mean, 187 +/- 26 (+/- SE) vs. 55 +/- 11 pmol/L; P less than 0.01]. The cancer patients had significantly higher insulin responses after glucose administration than normal women (sum of 1, 2, and 3 h postglucose values, 5545 +/- 1526 vs. 1444 +/- 156 pmol/L; P less than 0.02), even though their glucose responses were similar. Nests of luteinized cells, which were positive for testosterone by immunoperoxidase staining, were found in the ovarian stroma of 8 of the women with endometrial cancer, but in only 1 of those without cancer (P less than 0.01). Specific high affinity insulin receptors were demonstrable in the stroma of the postmenopausal ovaries. These results suggest that the frequency of stromal luteinization is increased in women with endometrial cancer and that insulin may play a role in the pathogenesis of this luteinization.

Androgen-stimulated pubertal growth: the effects of testosterone and dihydrotestosterone on growth hormone and insulin-like growth factor-I in the treatment of short stature and delayed puberty.

The purpose of this study was to investigate the roles of androgenic and estrogenic mechanisms in the stimulation of structural growth and plasma GH in male puberty. To resolve these two possible mechanisms, we compared the effect of two androgens in the treatment of constitutional delay in growth and adolescence: an aromatizable androgen, testosterone (T), and a nonaromatizable androgen, dihydrotestosterone (DHT). Nine adolescent males, Tanner stage 1 or 2, were studied before and during treatment with T enanthate (group A) or DHT heptanoate (group B). After 2.5 months of treatment, the height velocity (HV) was 12.6 +/- 2.8 cm/yr (n = 3) in group A and 8.9 +/- 1.7 cm/yr (n = 6) in group B, both within the range of peak HV for pubertal males. In group A, the integrated concentration of GH (ICGH) increased from 3.12 +/- 0.90 to 13.67 +/- 6.0 micrograms/L (P < 0.05), and plasma insulin-like growth factor-I (IGFI) increased from 126.7 +/- 2.5 to 350.3 +/- 20.3 micrograms/L (P < 0.01); plasma T increased from 0.8 +/- 0.5 to 33.8 +/- 11.0 nmol/L (P < 0.001), and the LH response to LHRH decreased from 27.6 +/- 10.7 to 5.9 +/- 2.5 IU/L (P = NS). In group B, ICGH decreased from 4.32 +/- 0.61 to 2.39 +/- 0.42 (P < 0.025), and IGF-I decreased from 218.3 +/- 39.2 to 184.0 +/- 15.8 (P = NS). Plasma T increased from 2.0 +/- 0.5 to 2.7 +/- 0.8 (P = NS), and the LH response to LHRH decreased from 45.7 +/- 14.5 to 10.7 +/- 5.8 (P < 0.05). To further evaluate the mechanism of the effect of DHT on plasma GH, seven male subjects with adolescent gynecomastia were treated with DHT heptanoate, and their responses were studied at 1 week and 3.5 months. ICGH decreased in conjunction with a decrease in the integrated T concentration (r = -0.77; P < 0.001) and to a slight degree with decreasing plasma estradiol (r = -0.39; P < 0.2). Plasma IGF-I did not show a significant change in the subjects with gynecomastia. Thus, the increase in GH at puberty in males appears to be due to an estrogen-dependent mechanism. The suppressive effect of DHT on GH secretion may be due to either suppression of estradiol production or a direct effect. Acceleration of HV into the peak pubertal range by DHT without an increase in plasma GH suggests that an increase in GH is not necessary for the pubertal growth spurt.

Effects of soya consumption for one month on steroid hormones in premenopausal women: implications for breast cancer risk reduction.

Soybean consumption is associated with reduced rates of breast, prostate, and colon cancer, which is possibly related to the presence of isoflavones that are weakly estrogenic and anticarcinogenic. We examined the effects of soya consumption on circulating steroid hormones in six healthy females 22-29 years of age. Starting within 6 days after the onset of menses, the subjects ingested a 12-oz portion of soymilk with each of three meals daily for 1 month on a metabolic unit. Daily isoflavone intakes were approximately 100 mg of daidzein (mostly as daidzin) and approximately 100 mg of genistein (mostly as genistin). Serum 17 beta-estradiol levels on cycle days 5-7, 12-14, and 20-22 decreased by 31% (P = 0.09), 81% (P = 0.03), and 49% (P = 0.02), respectively, during soya feeding. Decreases persisted for two or three menstrual cycles after withdrawal from soya feeding. The luteal phase progesterone levels decreased by 35% during soya feeding (P = 0.002). Dehydroepiandrosterone sulfate levels decreased progressively during soya feeding by 14-30% (P = 0.03). Menstrual cycle length was 28.3 +/- 1.9 days before soymilk feeding, increased to 31.8 +/- 5.1 days during the month of soymilk feeding (P = 0.06), remained increased at 32.7 +/- 8.4 days (P = 0.11) at one cycle after termination of soymilk feeding, and returned to pre-soya diet levels five to six cycles later. These results suggest that consumption of soya diets containing phytoestrogens may reduce circulating ovarian steroids and adrenal androgens and increase menstrual cycle length. Such effects may account at least in part for the decreased risk of breast cancer that has been associated with legume consumption.

Hormonal studies on adrenal-like tumor of the ovary--considerations on its histogenesis.

A case of adrenal-like tumor of the left ovary with peripheral and ovarian venous sex steroid levels is reported. High levels of androstenedione and testosterone together with normal levels of dehydroepiandrosterone and dehydroepiandrosterone-sulfate from the left ovarian vein infer a tumor derivation from transformation of the ovarian stromal cells.

Altered GLUT1 and GLUT3 gene expression and subcellular redistribution of GLUT4: protein in muscle from patients with acanthosis nigricans and severe insulin resistance.

Multiple isoforms of glucose transporters are found in muscle, the tissue that normally accounts for 85% of insulin-stimulated glucose uptake. Glucose uptake into muscle cells in the fasting state is mediated primarily by GLUT1 and GLUT3 glucose transporters, whereas postprandial (insulin-stimulated) and exercise-related increments in muscle glucose uptake are mediated primarily by GLUT4. To determine if glucose transporters are abnormally expressed in muscle from insulin-resistant subjects, muscle samples were obtained from 10 normal subjects and 6 obese, nondiabetic subjects with severe insulin resistance and acanthosis nigricans. Both GLUT4 total protein and mRNA were normal in the insulin-resistant subjects. Muscle GLUT3 protein and mRNA were lower than controls by 62% and 71%, respectively. GLUT1 mRNA was twice normal, whereas GLUT1 protein content was not significantly increased. GLUT4 protein was markedly redistributed to the muscle plasma membrane in subjects with severe insulin resistance compared with normals (92% v 40% GLUT4 in plasma membrane-enriched fractions, P <.001), whereas the percentage of GLUT1 and GLUT3 protein found in the plasma membrane-enriched fractions was not different from controls. These data document differences in the expression of genes for GLUT1 and GLUT3 in muscle from normal and insulin-resistant subjects. Further, insulin resistance with fasting hyperinsulinemia was associated with a redistribution of GLUT4 to the muscle cell surface with no change in total GLUT4 protein. These data suggest that glucose transporter gene expression and their basal distribution in human muscle are related to insulin resistance and could be determinants of whole body insulin responsiveness.

Steroid section patterns of a hilus cell tumor of the ovary.

Steroidogenic function of a locally invasive hilus cell tumor of the ovary was studied. Serum levels of testosterone, androstenedione, dihydrotestosterone, 17 alpha-hydroxyprogesterone, progesterone, and estradiol were measured in blood samples from the peripheral and the ovarian vein. The tumor was secreting all but estradiol. Concentrations of progesterone and 17 alpha-hydroxyprogesterone were greatly elevated. Testosterone and dihydrotestosterone were the predominant androgens secreted by the tumor. Estradiol concentrations were elevated but without a significant peripheral-ovarian gradient. Concentrations of all the steroids coming from the tumor were increased paradoxically in the peripheral circulation after administration of dexamethasone, and the tumor was responsive to stimulation by human chorionic gonadotropin.

Pregnancy and neurofibromatosis (von Recklinghausen's disease).

A case of neurofibromatosis adversely affected by pregnancy has been presented. The large neurofibromatosis lesions in this patient increased extensively during the latter part of pregnancy, mainly as the result of massive hemorrhage within the masses. Additionally, the patient developed partial paralysis of the lower extremities resulting in inability to walk. This was thought to be due either to the development of neurofibromatosis or to enlargement of a previously existing intraspinal small neurofibromatosis lesion. In view of exacerbation of von Recklinghausen's disease during pregnancy, as reported here and recorded by others, and its hereditary transmission (autosomal dominant gene), early termination of pregnancy and sterilization are recommended.

Hyperthecosis of the ovaries in acromegaly.

Clinical and endocrine features of a patient with ovarian hyperthecosis and a growth hormone-secreting pituitary tumor are reported. A 36-year-old nulliparous woman had a history of severe hirsutism and virilization of long duration. Ovarian catheterization studies at surgery confirmed an ovarian source of excessive androgen production. Ovarian pathology revealed stromal hyperthecosis. Growth hormone levels were elevated and could not be suppressed with glucose ingestion; a pneumoencephalogram revealed the presence of a pituitary tumor. The possible cause-and-effect relationship of these 2 relatively uncommon disorders is discussed.

In vivo steroid studies in luteoma of pregnancy.

Endocrine studies were performed in 2 cases of luteoma of pregnancy. Even though both luteomas were discovered incidentally at the time of postpartum tubal ligation and cesarean section, they were found to be functionally active, secreting several androgens. Steroid concentrations were measured in the ovarian vein blood draining the luteoma in one patient and in peripheral vein blood in both patients. Peripheral testosterone, androstenedione, and dihydrotestosterone concentrations were increased severalfold higher than the normal controls and were comparable to the concentrations reported previously in virilizing luteomas. Progesterone, 17 alpha-hydroxyprogesterone, and estradiol concentrations were increased as well. The concentrations in the ovarian vein were significantly greater than those in the peripheral vein, which indicates active secretion of these steroids by the luteoma. In spite of the high concentrations of androgens, neither the mothers nor the infants were virilized. Concentrations of androgenic steroids in the cord blood were in the normal range. Determination of steroid concentrations in the serum, taken at intervals post partum, indicated spontaneous regression of the luteomas.