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Biomedical subjects

B Runnebaum

Publications and source records attributed to B Runnebaum.

At least 181 records · Page 10Linked to original sources
PubMed1984

[Diagnosis of infertility in women wanting children].

The diagnosis of the female infertility is concentrated on five main points: monitoring of the female cycle, diagnosis of tubal, cervical, immunologic and psychosomatic factors. Outpointed is the endocrinological control in the female cycle and there disturbances. An important role in insufficiency of ovaries plays the hyperprolactinemic, the hyperandrogenemic and the thyroidogenic state. Also important for the diagnosis of female infertility are functional explorations like Metoclopramide and TRH tests.

Androgens↗
PubMed1984

New assay for steroid sulfatase (EC 3.1.6.2) and its application for studies of human placental and skin sulfatase.

A new, simple, fast and highly practicable sulfatase assay and its application is described. Sterol sulfatase sulfohydrolase (EC 3.1.6.2) activity is determined by a two-phase scintillation technique separating the unreacted [4-14C]dehydroepiandrosterone sulfate from carbon-14-labeled products. The principle of the separation relies on the limited emulsifying capacity of the dioxane-based scintillation solution for water and the different partition of dehydroepiandrosterone sulfate and sulfate-free steroid products between the scintillation fluid and the aqueous phase as recently applied for determination of aromatase activity [1]. [7-3H]Dehydroepiandrosterone sulfate can also be used as a substrate for this assay. This test was applied to studies of microsomal sulfatase prepared from human term placenta and to the detection of sulfatase activity in human skin biopsies. Using placental microsomes, the Km of dehydroepiandrosterone sulfate was determined to be 5.0 X 10(7)M. Sulfatase activity in frozen scrotal skin was found to be 2-3 fold than with vaginal skin. Using an incubation time of 24h/skin sulfatase can be detected in biopsies as small as 2.5 mm2. The sulfatase assay can be applied for routine detection of human placental sulfatase deficiency and, furthermore, the application of this assay has to be demonstrated for the analysis of sulfatase activity in patients with congenital ichthyosis (X-chromosomal, recessive type).

Carbon Radioisotopes↗
PubMed1984

Predictive value of hormone determinations in the first half of pregnancy.

In a prospective randomized study serial hormone determinations (beta-hCG, HPL, P, 17-OHP, E2 and E3) were performed with 1125 pregnant women from the detection of pregnancy until delivery (n = 994) or abortion (n = 131). In 605 women carrying to term blood sampling started before the 16th wk of gestation, while 389 patients were admitted to hospital between the 16th and 20th wk of gestation. The first value of most of the hormone determinations at the time of diagnosis of pregnancy before the 16th wk was normal in more than 90% (beta-hCG 95%, P 94%, E3 94%, E2 92%, HPL 64%). In the case of women with abortion the first hormone determination was low in more than 50% (beta-hCG 51%, P 56%, E3 54%, E2 62%, HPL 62%). The predictive value was highest for beta-hCG (75%) and E2 (70%) and lowest for HPL (18%). In 249 women with threatened abortion blood samples were obtained at the first days of bleeding. At this time the highest sensitivity in detecting early abortions (before the 16th wk of pregnancy) was 82% for E2, followed by beta-hCG 74%, E3 65%, P 63%, 17-OHP 52% and HPL 34% (n = 112). In late abortion (after the 16th wk of pregnancy, n = 19) the sensitivity of all methods tested was below 40%. In the case of women with bleeding and continuation of pregnancy (n = 118) normal values were found in 95% by P, 94% by beta-hCG, 93% by HPL and E3, and 83% by 17-OHP respectively. Serial determinations in women with abortion revealed that in a normal population trophoblastic disorders with reduced beta-hCG concentrations were most common. Of the remaining patients with normal beta-hCG concentrations every third woman had low P or E2 values. The combined determination of all hormones allowed conclusions to be drawn on the cause of pregnancy failure. It could be established that prior to the 6th wk of pregnancy the determination of beta-hCG was most valuable. From the 7th wk onwards the measurement of E2 or E3 showed the highest sensitivity. Between the 11th and 14th wk of pregnancy the discriminating potency of all methods tested was equally high. After the 14th wk of pregnancy hormone determinations were of little diagnostic value.

17-alpha-Hydroxyprogesterone↗
PubMed1984

Hormone load tests in the first half of pregnancy--a diagnostic and therapeutic approach.

In view of still unsolved problems concerning disturbances in early pregnancy, the efficacy of various substances with regard to endocrine systems in the first trimester of pregnancy has been investigated. Seventy-five women, who had been referred to our hospital for an authorized termination of pregnancy during weeks 7-9 of gestation, and 6 women between weeks 10 and 16 of gestation volunteered to take part in the study. After single administration of the test substances, blood was drawn from an indwelling catheter with one group of patients at hourly intervals over an 8-hour period, while with all other patients this was done at 3-hourly intervals over a 24-hour period. In all samples beta-HCG, progesterone (P), estradiol-17 beta (E2), and 17 alpha-hydroxyprogesterone (17-OHP) were determined. The following substances were studied in detail: HCG, allylestrenol, 17-hydroxyprogesterone caproate, tamoxifene, R 5020, betamethasone, and dehydroepiandrosterone sulfate (DHAS). Two hundred and seventy-one women with imminent abortion were either treated with allylestrenol (n = 130) or simple clinotherapy and no medication (n = 141). One hundred and two women had a miscarriage, while 168 carried to term. The serum concentrations of beta-HCG, P, E2 and estriol (E3) were determined serially. Twelve women with a history of repeated miscarriages were treated with vaginal progesterone suppositories. Five of them experienced another miscarriage. The serum concentrations of beta-HCG and P were determined serially. It could be shown that diagnostics in early pregnancy have been complemented by assessment of the E2-increase after DHAS loading. Maternal serum concentrations were not affected by administration of HCG and various progestational agents including allylestrenol. Only in the case of parenteral or vaginal application of progesterone could increased serum concentrations of this hormone be demonstrated. Progesterone substitution in early pregnancy may, therefore, be chosen under special conditions as possible therapeutic procedure.

17 alpha-Hydroxyprogesterone Caproate↗
PubMed1984

Inhibition of human placental progesterone synthesis by danazol in vivo.

In vivo, a single dose of 1000 mg danazol was given orally to pregnant volunteers (n = 8) prior to a therapeutic abortion (8th-12th week of gestation). Changes in serum progesterone and estradiol were evaluated both by analysis of percentage values related to initial concentrations or statistically by a Kruskal-Wallis test comparing absolute steroid concentrations. Following treatment (n = 8), a significant decrease in mean plasma progesterone of about 20% was observed within 2-4 hours; progesterone levels varied between 80-120% during 24 hours in controls (n = 10); individual serum estradiol decreased up to 30% of control values 2 hours after danazol application. Changes in estradiol in controls versus tests were not statistically significant (p less than 0.05) when absolute estradiol concentrations were compared. Only a slight (10-20%) decrease in mean serum DHAS was found between 2 to 6 hours following danazol treatment. This study demonstrates the inhibitory activity of danazol on the human maternal and fetal steroidogenesis in vivo. The possible sites of action of danazol are discussed.

Abortion, Therapeutic↗
PubMed1984

Human low density lipoproteins (LDL) in combination with cholesterol or cholesteryl linoleate as precursors for progesterone synthesis of human placenta in organ culture.

After preincubation of term placental tissue in organ culture for 24 h, progesterone synthesis is 2-3 fold lower than without preincubation. By adding human male serum proteins (MW less than 12,400), we obtained 2-3.5 fold lower tissue levels of progesterone. Serum proteins with high molecular weight (MW greater than 12,400) are postulated to facilitate progesterone release by binding free medium progesterone. In test series without preincubation, there are no significant (p less than 0.05) differences in progesterone formation in the presence of cholesterol (C), cholesteryl linoleate (CL), and LDL. In test series with preincubation, LDL causes a twofold increase in medium progesterone with C (0.1 and 1 mM) and CL (0.1 mM) in the presence of the low molecular weight serum protein (MW less than 12,400) solution. A decrease of 50% was obtained by 1 mM CL with/and without LDL. In culture medium containing high molecular weight serum proteins (MW greater than 12,400), 0.1 and 1 mM C and CL induce a twofold increase in progesterone production without any significant (p less than 0.05) differences between the single values. No further stimulation could be observed by LDL because there was sufficient LDL for maximal progesterone formation. In conclusion, LDL enhances the utilization of cholesterol and cholesteryl linoleate for progesterone production in term placenta. A lipoprotein cholesterol receptor is suspected.

Cholesterol↗
PubMed1983

Inhibition of human placental progesterone and estrogen synthesis in early human gestation by aminoglutethimide in vivo.

The inhibitory effect of d,l-aminoglutethimide (AG) on the synthesis of progesterone and estradiol in early human pregnancy (8th-12th week of gestation) was investigated in volunteers; control group (n = 11), AG group [1000 mg AG orally at test begin (n = 6)]. Venous blood samples were taken at the beginning of the test and 0.5, 1, 2, 4, 8 and 24 h thereafter. In controls, no significant changes in serum progesterone and estradiol could be observed during 24 h. In the AG group, a decrease in progesterone and estradiol could be observed within 1 h after the test began; lowest serum steroid concentrations were reached after 4 h. Relative to the initial values taken as 100%, the greatest decrease in progesterone ranged between 37 and 83%, 62 +/- 15% (means +/- SD)(n = 6); the greatest decrease in estradiol ranged between 32 and 78%, 51 +/- 17% (means +/- SD)(n = 6). Twenty four hours after AG treatment, both steroids reached similar concentrations to those found at test begin. No clinical signs (e.g. uterine bleeding, contractions) for the abortifacient action of AG were observed. In conclusion, a single dose of AG (1000 mg given orally) cannot induce a therapeutic abortion in early pregnancy. In accordance with in vitro studies, the inhibitory effect of AG on placental progesterone formation is due to an inhibition of mitochondrial cholesterol side chain cleavage. The decrease in estradiol is thought to be related to an inhibition of placental aromatase.

Aminoglutethimide↗
PubMed1983

Characterization of human cholesterol side chain cleavage enzyme (EC 1.14.15x) of human term placental mitochondria.

The cholesterol side chain cleavage enzyme (EC 1.14.15x) in mitochondria of a human term placenta was partially characterized. Enzyme activity was determined by separation of [26-14C]-cholesterol and [5-14C]-isocaproic acid formed by side chain cleavage. Since the amounts of unlabeled cholesterol were too large, a KM of cholesterol could not be determined. The apparent KM value of NADPH is 6.25 x 10(-4) M. A pH optimum was found at pH 9.5 (Tris buffer) and a temperature optimum at 40 C. The metal ions Sr2+ and Ba2+ showed no inhibition at 1 and 10 mM and a moderate inhibition at 100 mM. In low concentrations (1 mM), Mg2+ and Ca2+ slightly stimulated the enzyme whereas in higher concentrations (100 mM) an inhibitory effect was observed. A strong inhibition was achieved with 1 mM Zn2+, Cd2+, Cu2+ and by 10 and 100 mM Fe2+, Mn2+, Co2+ and Ni2+. During preincubation of the enzyme without radioactive substrate, a rapid loss in enzyme activity in relation to enzyme concentration was observed (initial activity = 100%) (preincubation time in hours): 0.5 h (97%), 1 h (55%) and 1.5 h (34%). A dose-dependent inhibition of the enzyme by the following proteins was achieved: bovine serum protein, human serum protein, human immunoglobulin G and ovalbumin. Furthermore, a dose-dependent inhibition was found with the membrane lipids lecithin and sphingosine.

Cholesterol Side-Chain Cleavage Enzyme↗
PubMed1983

Influence of severe obesity on peripheral hormone concentrations in pre- and postmenopausal women.

To investigate the influence of obesity on hormonal parameters in 186 apparently healthy women and in 176 women suffering from severe obesity the serum concentrations of FSH, LH, estrone (E1), estradiol (E2), androstenedione (A) and testosterone (T) were determined radioimmunologically. The climacteric onset of increased FSH production is 4 yr earlier (P less than 0.001) in obese than in normal women. Parallel to the rise of FSH there is a significantly premature decrease of the E1 and E2 concentrations in obese women. The typical elevation of the LH was found similar and not significantly different in the two collectives. The mean A levels are significantly lower (P less than 0.01) in obese than in normal women in all age groups. The T concentrations do not depend on the age of the women during the investigated period (41 to 60 yr) and are significantly higher (P less than 0.001) in the obese than in the normal women. There is a significant (P less than 0.001) correlation between the concentrations of A and E1 both in the obese and the normal women. An increased conversion of androgens to estrogens by adipose tissue is not revealed by the peripheral serum concentrations. Our data clearly demonstrate that in obese women the onset of ovarian insufficiency is significantly earlier than in normal women.

Adult↗
PubMed1983

Inhibition of human placental progesterone synthesis and aromatase activity by synthetic steroidogenic inhibitors in vitro.

The inhibitory effect in vitro of four synthetic steroids on enzyme systems of placental progesterone synthesis at term was analyzed. Cholesterol side chain cleavage enzyme (CSCC) was not influenced by azastene, trilostane, and WIN 32,729. A 50% inhibition of CSCC was found by 10 microM cyanoketone. The 3 beta-hydroxysteroid dehydrogenase was dose-dependently inhibited by azastene (I50 = 1 microM, trilostane (I50 = 4 nM), cyanoketone (I50 = 3 nM), and WIN 32,729 (I50 = 5 nM). A competitive inhibition of the 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSDH) by azastene (I50 = 0.6 microM), trilostane (I50 = 4.1 microM), cyanoketone (I50 = 0.6 microM), and WIN 32,729 (I50 = 1.5 microM) was observed. No difference in the effect of steroids on the 20 alpha-HSDH of early gestational and term placenta was found. The four steroidogenic inhibitors did not affect the activity of placental aromatase in vitro. Our results allow a comparison of inhibitory potencies of four steroidogenic inhibitors on different steroidogenic enzymes in vitro.

20-Hydroxysteroid Dehydrogenases↗
PubMed1983

Inhibition of human placental progesterone synthesis by danazol in vitro.

In vitro, danazol showed a slight dose-dependent inhibition of the mitochondrial cholesterol side chain cleavage enzyme isolated from early gestational (8th to 12th week of gestation) placenta. In the presence of 100 microM danazol, the enzyme activity was 65% of controls. Danazol inhibits dose-dependently the mitochondrial 3 beta-hydroxysteroid dehydrogenase (I50 = 3.1 microM; Ki = 1 microM) (noncompetitive inhibition) and the cytoplasmic 20 alpha-hydroxysteroid dehydrogenase (I50 = 1.4 microM; Ki = 2.6 microM) (competitive inhibition). The inhibition of human placental progesterone synthesis by danazol in vitro is a further example for the direct interference of danazol with steroidogenesis.

20-Hydroxysteroid Dehydrogenases↗
PubMed1983

[Regulation of human placental progesterone synthesis].

The steroid hormone progesterone is necessary for the maintenance of human pregnancy. It protects the uterus against the labour-inducing effect of prostaglandins and oxytocine. Before the 8.-9th week of gestation progesterone is produced by the corpus luteum and thereafter by the human placenta. The progesterone production of the human placenta is widely independent of endocrine organs of the mother and the foetus and controlled by autoregulation. Progesterone is formed from cholesterol taken up from the maternal circulation in the form of lipoprotein complexes. After side-chain cleavage of cholesterol pregnenolone is formed, which is converted by a 3 beat-hydroxysteroid dehydrogenase, delta 4-5 isomerase to progesterone. Progesterone is released partly to the mother and via the umbilical cord to the foetus. In the foetus a high conversion to 20 alpha-dihydroprogesterone takes place and this compound is transported to the placenta and recycled to progesterone. The steroidogenic enzymes of the progesterone pathway are controlled by various feedback inhibitions; activators could not be isolated so far.

Cholesterol↗
PubMed1983

[Ectopic pregnancy--significance of serum human chorionic beta gonadotropins and beta-1-glycoprotein (SP1) determination].

In 83 patients with an ectopic pregnancy the serum levels of HCG and the pregnancy specific beta 1 glycoprotein SP-1 were determined. In addition the serum levels of 25 patients with a nonviable pregnancy and 26 non-pregnant patients were determined. The radio-immunologic beta HCG and SP-1 tests and the enzyme immunologic Sp-1 test were used. The radio-immune assay of beta HCG diagnosed 96% of all cases with an ectopic pregnancy. The enzyme and radio-immunologic SP-1 tests failed to diagnose the ectopic pregnancy in 5 of 83 cases (6%) by the Elisa test and in 3 of 83 cases (4%) by the RIA test. The lower limit of diagnosis of pregnancy was considered to be 1.8 micrograms SP-1/1. The concomitant determination of the beta HCG and the SP-1 level permits the diagnosis of ectopic pregnancy in all cases. The main advantage of the enzyme immunologic determination compared to the radio-immunologic determination is at present the materially shorter time factor of the test and the fact that an isotope laboratory is not necessary.

Chorionic Gonadotropin↗
PubMed1983

Diagnosis of intrauterine fetal growth retardation (IUGR) and placental insufficiency by a dehydroepiandrosterone sulfate (DHAS) loading test.

Chronic placental insufficiency results in intrauterine fetal growth retardation (IUGR). The IUGR can be diagnosed by clinical signs (follow-up of maternal weight, fundus height, abdominal circumference), ultrasound examination (biparietal and thoracic diameters, circumferences of the head and the trunk), and by endocrinologic tests (estrogen determination in serum and urine without and after performance of a DHAS loading test). The different ways of performing the DHAS loading test reported in the literature are reviewed. The DHAS loading test measures the aromatization capacity of the human placenta and indirectly its metabolic exchange capacities. After DHAS loading, estrogens (estrone, estradiol, estriol), DHAS and DHA can be determined in blood and urine; furthermore, changes in urine total estrogen excretion can be evaluated. In conclusion, the best parameter for diagnosing IUGR seems to be the determination of the DHAS half-life after DHAS loading. A prolongation of DHAS half-life (greater than 4.7 h) after DHAS loading (50 mg i.v.) is a good index of IUGR.

Circadian Rhythm↗
PubMed1983

Sulfatase deficiency in the human placenta: clinical findings.

Sulfatase and aromatase are the key enzymes of estrogen biosynthesis in the human placenta. A total of 76 pregnancies with sulfatase deficiency have been reported. Reduced sulfatase activity occurs in 1:2000 of 1:6000 pregnancies. It can be suspected in patients with low urinary excretion or low serum estriol levels. The sulfatase deficiency can be detected during pregnancy by a prolongation of the half-life of dehydroepiandrosterone sulfate (DHAS) after venous DHAS loading (50 or 100 mg). Post partum the placental sulfatase deficiency can be demonstrated in vitro by nonconversion of radioactive DHAS to DHA. Only 7 of the 76 pregnancies described ended with an uncomplicated vaginal delivery after spontaneous onset of labor. A cesarian section was required in 18 cases. The other case reports mostly concern patients associated with a prolonged pregnancy, lack of cervical dilatation, or absent induction of labor. All 76 newborns were male. Sulfatase deficiency is probably a congenital, sex-specific, X-linked placental enzyme defect. A special therapy is not necessary but the antepartum diagnosis is important because this benign disorder has to be discriminated from the more serious fetal adrenal hypoplasia.

Estriol↗