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: ObjectiveTo test the hypothesis that adrenal androgen (AA) excess in the polycystic ovary syndrome (PCOS) is due to a generalized exaggeration in AA output in response to adrenocorticotropic hormone (ACTH), and that this abnormality is due to an identifiable alteration in the biosynthesis of AAs.: DesignCross-sectional prospective controlled study.: SettingAcademic tertiary care medical center.: Patient(s)Patients with PCOS (n = 9) and without (n = 9) AA excess and controls (n = 12) without hyperandrogenism, matched for age and body mass.: Intervention(s)Acute 60-minute ACTH test was performed on patients.: Main outcome measure(s)Basal levels of dehydroepiandrosterone sulfate (DHEAS), total testosterone (T), free T, and basal (Steroid0) and the 60-minute ACTH-stimulated levels (Steroid60) of pregnenolone (PREG), progesterone (P4), 17-hydroxypregnenolone (17-HPREG), 17-hydroxyprogesterone (17-HP), dehydroepiandrosterone (DHEA), and androstenedione (A4) were measured. Adrenocortical activities of 17-hydroxylase (17-OH), 17,20-lyase, and 3β-hydroxysteroid dehydrogenase were estimated from product to precursor ratio, using Steroid60 values.: Result(s)Compared with PCOS patients without AA excess, PCOS patients with AA excess demonstrated significantly greater levels of DHEA0 and A460. PCOS patients with AA excess had significantly higher activity of Δ517-OH, compared with PCOS patients without AA excess.: Conclusion(s)Adrenal androgen excess in PCOS is associated with a greater Δ517-OH activity in response to ACTH. [Copyright &y& Elsevier]

: ObjectiveTo determine if insulin or glucose action plays a role in adrenocortical steroidogenesis in the polycystic ovary syndrome (PCOS).: DesignProspective cohort study.: SettingAcademic medical center.: Patient(s)Nine reproductive-aged patients with PCOS and nine age-, race-, and body mass index–matched controls.: Main outcome measure(s)Insulin-modified frequently sampled intravenous glucose tolerance testing and an acute 60-minute ACTH-(1-24) stimulation test. From the glucose tolerance test, glucose and insulin were measured and the insulin sensitivity index, glucose effectiveness, and acute insulin response to glucose were determined. Dehydroepiandrosterone sulfate (DHEAS) basally and 17-hydroxypregnenolone, 17-hydroxyprogesterone, DHEA, androstenedione, and cortisol during ACTH testing at 0 and 60 minute (steroid0 and steroid60) were determined. The net change in steroid during the ACTH test was calculated.: Result(s)The insulin sensitivity index had limited correlation with adrenocortical variables in both groups. In patients with PCOS, glucose effectiveness was positively associated with DHEAS, cortisol0, cortisol60, change in cortisol, DHEA0, DHEA60, change in DHEA, 17-hydroxyprenenolone60, change in 17-hydroxypregnenolone, DHEA0, androstenedione0, 17-hydroxyprenenolone0, 17-hydroxyprogesterone0, 17-hydroxyprenenolone60, and 17-hydroxyprogesterone60.: Conclusion(s)Adrenocortical biosynthesis, basally and in response to ACTH, appears to be closely associated with glucose effectiveness in PCOS. A common factor determining both the effectiveness of glucose to control its own production or uptake and adrenocortical biosynthesis may be aberrant in PCOS. [Copyright &y& Elsevier]

Objective: To determine whether the use of oral micronized progesterone (OMP) to induce withdrawal bleeding in women suspected of having polycystic ovary syndrome (PCOS) alters circulating androgen levels.Design: Prospective clinical trial.Setting: Academic medical center.Patient(s): Eight reproductive-aged women with PCOS.Intervention(s): Blood was sampled before (week 0) and weekly after (weeks 1 to 4) the administration of OMP (Prometrium, Solvay Pharmaceuticals, Marietta, GA), 100 mg in the morning and 200 mg before bedtime for 7 days.Main Outcome Measure(s): The levels of total testosterone (TT), free testosterone (FT), sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), and androstenedione (A4) were determined in the blood samples.Result(s): In seven of the eight women studied, menstrual cycle intervals were >3 months, while one was eumenorrheic; six of the eight women had hirsutism (modified Ferriman-Gallwey score >7). Mean age was 28.9 +/- 10.4 years and mean body mass index was 33.9 +/- 4.7 kg/m2. The mean values of TT, FT, SHBG, DHEAS, A4, and 17-OHP did not change with OMP administration. However, a higher 17-OHP level was observable at the completion of OMP administration (week 2).Conclusion(s): We conclude that the administration of OMP (100 mg in the morning and 200 mg before bedtime for 7 days) to induce withdrawal bleeding in women with PCOS does not significantly alter circulating androgen or 17-OHP levels, and can be used to time blood sampling in these patients. [ABSTRACT FROM AUTHOR]

Objective: To test the hypothesis that adrenal steroidogenesis in nonclassic adrenal hyperplasia (NCAH) patients is, at least in part, independent of adrenocorticotropic hormone (ACTH) control.Design: Prospective controlled clinical study.Setting: Patients and healthy volunteers in an academic research environment.Patient(s): Four patients with 21-hydroxylase (21-OH) deficient NCAH and four healthy control women.Intervention(s): Patients received the long-acting gonadotropin-releasing hormone analog (GnRH-a) leuprolide acetate (3.75 mg/month IM) on weeks 0 and 4; and dexamethasone (DEX) in weekly incremented doses (0.25 mg/day, 0.50 mg/day, 1.0 mg/day, and 1.5 mg/day), beginning on weeks 4, 5, 6, and 7, respectively.Main Outcome Measure(s): The levels of 17-hydroxyprogesterone (17-HP), progesterone (P4), androstenedione (A4), dehydroepiandrosterone sulfate (DHS), and cortisol (F) were measured at the beginning of weeks 0, 4, 5, 6, 7, and at the end of the study (beginning of week 8).Result(s): Patients and controls had a similar median age and body mass index (BMI). There were no significant decreases in the median levels of the studied hormones following 4 weeks of treatment with GnRH-a only, in either NCAH patients or controls. Analysis of individual hormonal values demonstrated that by the end of the study (after DEX of 1.5 mg/day during a week) only 2 of 4, 0 of 4, 3 of 4 and 3 of 4 NCAH patients had 17-HP, P4, A4, and DHS levels within the range of control values, respectively.Conclusion(s): Ovarian and incremental adrenal suppression did not fully suppress progestogen and androgen production in all of the study patients with 21-OH-deficient NCAH, suggesting that their production was partially independent of ACTH stimulation. Potentially in these patients subtle degrees of adrenocortical hyperplasia and/or abnormal enzymatic kinetics are responsible for the nonsupressibility. [ABSTRACT FROM AUTHOR]

Abstract: The presence in Entamoeba histolytica of a fibronectin (FN) receptor, which is antigenically related to β1 integrin-like molecules and shows 99% homology with the intermediate subunit-2 of the Gal/GalNAc-specific lectin has been described. The E. histolytica genome has been sequenced, and its analysis shows no integrin sequences. Here we provide further evidence to demonstrate that this molecule behaves as integrin-like in its physical, structural and functional properties. The purified β1EhFNR complex is resolved into three polypeptides of 150, 140, and 130kDa. Transmission electron microscopy showed individual complexes consisting of oblong heads of 3nm×4nm and two projecting arms 6–7nm in length. In the absence of detergent, these complexes formed aggregates that were composed of clusters or “rosettes” of between two and six or more β1EhFNR complexes. The physical properties of the purified β1EhFNR complexes were: R S =5.8nm, S 20 W =8.3, f/f 0 =1.4. This complex was seen in close physical association with adhesion plates and phagocytic invaginations, using confocal microscopy and the 3C10 mAb that recognizes these three subunits complex. Regulation of its surface expression is not dependent on protein synthesis; rather it is regulated by inward and outward mobilization of the molecules. The presence and antigenic similarity of putative β1EhFNRs in different strains and species of Entamoeba was analyzed using the 3C10 mAb; this mAb recognized the complex in all E. histolytica species, however there was no recognition in E. dispar, E. invadens, and Laredo strains. Finally, evidence is provided about post-translational modifications such as tyrosine phosphorylation and glycosylation suffered by the β1EhFNR complex. [Copyright &y& Elsevier]