Yong Siow

Relationship between serum müllerian-inhibiting substance and other reproductive hormones in untreated women with polycystic ovary syndrome and normal women

OBJECTIVE To examine the relationship of serum müllerian-inhibiting substance (MIS), E(2), free-T, LH, and FSH in untreated women with polycystic ovary syndrome (PCOS) and in women with normal menstrual cycles. DESIGN A prospective study. SETTING University Departments of Obstetrics and Gynecology and Surgery. PATIENT(S) Twenty-seven women with PCOS and 20 women with normal menstrual cycles. INTERVENTION(S) Serum was collected from women with PCOS and from normal women during the early follicular phase of the menstrual cycle, stored frozen until assayed. MAIN OUTCOME MEASURE(S) Serum levels of MIS, E(2), free-T, TSH, LH, and FSH were measured. RESULT(S) Serum müllerian-inhibiting substance levels in PCOS patients were significantly higher compared with normal women (+/- SE; 5.3 +/- 0.7 and 1.4 +/- 0.2 ng/mL, respectively). An inverse correlation (r = -0.5965) was found between serum levels of MIS and E(2) in PCOS women, but not in normal women. Women with PCOS had higher serum LH levels than those of normal women (15.2 +/- 1.2 and 5.0 +/- 0.7 mIU/mL). CONCLUSION In this study, women with PCOS have significantly higher serum MIS levels than normal women. The inverse relationship between müllerian-inhibiting substance and E(2) levels suggests that MIS may modulate ovarian E(2) synthesis and have a role in the disordered folliculogenesis characteristic of PCOS.

Serum mullerian-inhibiting substance levels during normal menstrual cycles

OBJECTIVE To measure serum levels of müllerian-inhibiting substance (MIS) during the normal menstrual cycle. DESIGN Serum was collected from women during ovulation and the mid-luteal and early follicular phases of the menstrual cycles. It was stored frozen at -80 degrees C until assayed. SETTING University of Louisville Departments of Obstetrics and Gynecology and Surgery. PATIENT(S) Twenty healthy women 22-35 years of age with normal menstrual cycles. INTERVENTION(S) Blood samples were collected on menstrual cycle day two or three and on the day of LH surge plus one and plus seven or eight. MAIN OUTCOME MEASURE(S) Serum MIS levels were measured by using an enzyme-linked immunosorbent assay. RESULT(S) Serum MIS levels ranged from a low of 1.4 +/- 0.9 ng/mL (mean [+/-SD]) in the early follicular phase, peaked mid-cycle at 1.7 +/- 1.1 ng/mL, and decreased to 1.4 +/- 0.9 ng/mL in the mid-luteal phase of the normal menstrual cycle. CONCLUSION(S) Fluctuations in serum MIS levels during the menstrual cycle suggest that MIS may have a regulatory role in folliculogenesis.

Müllerian-inhibiting substance in follicular fluid and serum: a comparison of patients with tubal factor infertility, polycystic ovary syndrome, and endometriosis

OBJECTIVE To determine Müllerian inhibiting substance (MIS) levels in follicular fluid (FF) and sera of IVF patients. DESIGN Prospective study. SETTING Fertility center. PATIENT(S) Sixty-six patients: 20 with tubal factor infertility, 17 with polycystic ovary syndrome (PCOS), and 29 with endometriosis. INTERVENTION(S) All patients underwent ovarian stimulation with hMG and/or FSH, as well as oocyte retrieval for IVF. MAIN OUTCOME MEASURE(S) Follicular fluid and serum MIS levels and oocyte fertilization rates. RESULT(S) Levels of MIS in FF and sera of PCOS patients were significantly higher than those in tubal factor patients: 7.01 +/- 1.52 versus 1.65 +/- 0.23 ng/mL (mean +/- SE) and 2.97 +/- 0.52 versus 0.92 +/- 0.19 ng/mL, respectively. In endometriosis patients, follicular fluid and serum MIS levels were not significantly different from those in tubal factor patients. In PCOS patients, the percentage of immature oocytes retrieved (17.9% +/- 5.0%) was significantly higher compared with tubal factor (1.5% +/- 1.0%) and endometriosis (9.2% +/- 2.3%) patients. The percentage of oocytes fertilize was significantly lower in PCOS patients (30.2% +/- 5.3%) compared with tubal factor (62.2% +/- 5.5%) and endometriosis (37.5% +/- 5.7%) patients. CONCLUSION(S) Women with PCOS had higher serum and follicular fluid MIS levels, a higher percentage of immature oocytes, and lower fertilization rates than women with endometriosis or pelvic adhesions.

Diabetes-induced bile acid composition changes in rat bile determined by high performance liquid chromatography.

The distribution of glycine and taurine conjugated bile acids in bile from streptozotocin-induced diabetic rats were determined by high performance liquid chromatography (HPLC). Biliary bile acid output in diabetic rats was significantly greater compared to control (p less than 0.001). The increase is not a generalized effect of diabetes, but is the preferential increased production of taurochenodeoxycholic acid. These observed changes in bile acid composition may represent greater capacity of bile from diabetic rats to solubilize cholesterol. In the absence of a gallbladder, however, rat bile undergo continuous enterohepatic circulation, and consequently is not subjected to modifications by gallbladder epithelial cells that would potentiate cholesterol precipitation.

Reversible bile acid changes in bile duct obstruction and its potential for hepatocellular injury

The etiology of hepatocellular dysfunction resulting from chronic biliary obstruction is not clearly understood. Alterations in bile acid metabolism due to changes in microsomal cytochrome P-450 enzyme activities may have a fundamental role in cholestatic liver injury. This study examines the very early changes in both biliary bile acids and hepatic microsomal cytochrome P-450 content after bile duct obstruction in the rat and the effects of the restoration of bile flow after 3 days of biliary obstruction. We found that early induction of cytochrome P-450 may be a fundamental step in the generation of cholestatic liver injury mediated by hepatotoxic bile acids. The rapid reversal of bile acid changes with reconstituted bile flow indicate that the liver is able to quickly recover when obstruction is relieved. Characterization of this fundamental process may ultimately provide a means of modulation of cholestatic hepatotoxicity.

Changes in intragastric bile acid composition in patients receiving cimetidine postoperatively

Enterogastric reflux has been implicated as a possible etiologic mechanism in gastritis both after partial gastrectomy and in those with an intact pylorus. We studied the effects of cimetidine on bile acid concentration and composition by high-performance liquid chromatography. The gastric aspirates collected for this study came from 27 prospectively randomized patients receiving intravenous cimetidine (200 mg every 6 hours) and 25 patients given a placebo. Total bile acid concentration of aspirates was determined spectrophotometrically. Marked differences were noted in conjugated bile acids. Glycochenodeoxycholic acid, a toxic dihydroxy bile acid, was decreased after cimetidine compared with results from the placebo. The ratio of less toxic trihydroxylated to more toxic dihydroxylated bile acids was significantly increased. Enterogastric reflux itself seemed unaltered by cimetidine; likewise, the concentration of total bile acids in the cimetidine group was similar to that among patients receiving placebo. These changes in bile salt composition with cimetidine may help explain its salutary effects in gastritis, over and above its ability to reduce gastric hydrogen ion secretion.

Circulating Prolidase Activity in Patients with Myocardial Infarction

Background Collagen is a major determinant of atherosclerotic plaque stability. Thus, identification of differences in enzymes that regulate collagen integrity could be useful for predicting susceptibility to atherothrombosis or for diagnosing plaque rupture. In this study, we sought to determine whether prolidase, the rate-limiting enzyme of collagen turnover, differs in human subjects with acute myocardial infarction (MI) versus those with stable coronary artery disease (CAD). Methods We measured serum prolidase activity in 15 patients with stable CAD and 49 patients with acute MI, of which a subset had clearly defined thrombotic MI (n = 22) or non-thrombotic MI (n = 12). Prolidase activity was compared across study time points (at cardiac catheterization, T0; 6 h after presentation, T6; and at a quiescent follow-up, Tf/u) in acute MI and stable CAD subjects. We performed subgroup analyses to evaluate prolidase activity in subjects presenting with acute thrombotic versus non-thrombotic MI. Results Although prolidase activity was lower at T0 and T6 versus the quiescent phase in acute MI and stable CAD subjects (p < 0.0001), it was not significantly different between acute MI and stable CAD subjects at any time point (T0, T6, and Tf/u) or between thrombotic and non-thrombotic MI groups. Preliminary data from stratified analyses of a small number of diabetic subjects (n = 8) suggested lower prolidase activity in diabetic acute MI subjects compared with non-diabetic acute MI subjects (p = 0.02). Conclusion Circulating prolidase is not significantly different between patients with acute MI and stable CAD or between patients with thrombotic and non-thrombotic MI. Further studies are required to determine if diabetes significantly affects prolidase activity and how this might relate to the risk of MI.