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Biomedical subjects

B Runnebaum

Publications and source records attributed to B Runnebaum.

At least 199 records · Page 11Linked to original sources
PubMed1983

Influence of human lipoproteins on the progesterone synthesis of human term placenta in organ culture.

In the presence of LDL (200 micrograms/ml) and HDL (400 micrograms/ml), the uptake of radioactive cholesterol by a human term placenta in organ culture was enhanced by about 1.5 and 2.5, respectively, after 24-h incubation. Using cholesterol linoleate, the ratio was 1.0 and 1.5, and the tissue concentration of progesterone was 5-fold higher in the presence of LDL (600 micrograms/ml) than in the presence of HDL (4.4 mg/ml). A dose-dependent increase in medium progesterone was found using either LDL or HDL in combination with cholesterol or cholesterol linoleate, respectively. In human term placenta in organ culture, the human lipoproteins LDL and HDL both have a carrier function for cholesterol and cholesteryl linoleate, stimulate the uptake of these steroids in the placental tissue, and enhance placental progesterone formation. Furthermore, the lipoproteins facilitate progesterone release from the placental tissue.

Cholesterol↗
PubMed1982

Partial characterization of the cytoplasmic 20 alpha-hydroxysteroid dehydrogenase (EC 1.1.1.149) of the human placenta at term.

The 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSDH) is a key enzyme in human fetal and maternal progesterone metabolism. In this paper, the cytoplasmic 20 alpha-HSDH of human term placenta is partially characterized in vitro. A 14-fold concentration of the 20 alpha-HSDH was prepared by ultracentrifugation and ammonium sulfate precipitation. The apparent Km values for the substrates progesterone (Km: 4.8 x 10(-5) M) and 20 alpha-DHP (Km: 6.2 x 10(-5) M) and for the cofactors NADPH (Km: 1.9 x 10(-4)) and NADH (Km: 2.6 x 10(-4)) were determined. The temperature optimum for the oxidation of 20 alpha-DHP is 40--50 degrees C. The pH optimum for the reduction of progesterone was found to be pH 6.2 and for the oxidation of 20 alpha-DHP pH 6.5. The addition of glycerol (3 M) to the incubation medium inhibited the conversion rate of 20 alpha-HSDH by 70%. No influence of EDTA could be found. Various bivalent metal ions (1--100 mM) showed a dose-dependent inhibition of 20 alpha-HSDH; a complete inhibition was achieved at 100 mM: Cu2+, Zn2+, Cd2+, Fe2+ and Ni2+.

20-Hydroxysteroid Dehydrogenases↗
PubMed1982

Endogenous inhibition of the 20 alpha-hydroxysteroid dehydrogenase (EC 1.1.1.149) in the human term placenta in vitro.

Human placental 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSDH) interconverts progesterone and 20 alpha-dihydroprogesterone (20 alpha-DHP). In this study, an endogenous inhibitor of the cytoplasmic 20 alpha-HSDH isolated from human term placenta is demonstrated. Characterization of the endogenous inhibitor was carried out by adding heat-denatured fractions of the 20 alpha-HSDH enzyme stock solution to the incubations. The aqueous phase of the 20 alpha-HSDH (after diethylether extraction) using 8-fold concentration of the enzyme inhibited the 20 alpha-HSDH activity by 50%. After ultrafiltration of the aqueous phase, this inhibitory effect (50%) was found in the aqueous fraction with a molecular weight above 12,800. No inhibition of the 20 alpha-HSDH was shown using the ether phase or the aqueous ultrafiltrate with a molecular weight below 12,800. The 20 alpha-HSDH was stimulated by human and bovine serum albumins up to 290% and 420% respectively. Bovine serum albumin showed a higher stimulatory effect on the oxidative (420%) than on the reductive (190%) pathway of the 20 alpha-HSDH. Ovalbumin and immunoglobulin G had no effect. The endogenous inhibitor of the cytoplasmic 20 alpha-HSDH isolated from the human term placenta is heat stable (100 degrees C), water soluble, not soluble in diethylether and has a molecular weight above 12,800. The stimulatory effect of serum albumins in 20 alpha-HSDH may be caused by binding and inactivation of the endogenous inhibitor.

20-Hydroxysteroid Dehydrogenases↗
PubMed1982

New aromatase assay and its application for inhibitory studies of aminoglutethimide on microsomes of human term placenta.

A new, simple, fast and highly practicable aromatase assay and its application is described. This test depends on the release of tritiated water after aromatization of [1 beta,2 beta-3H]- or [1,2-3H]-androstendione or testosterone. In tests with [1 beta,2 beta-3H]-androstendione, nonradioactivity labeled estrogens are formed whereas in tests using [1,2-3H]-androstendione as substrate both estrogens and water contain tritium atoms. Tritiated water is determined by a two-phase scintillation technique depending on the limited emulsifying capacity of dioxane-based scintillation solution for water. A small volume (0.1 ml) of water is completely emulsified by the scintillation solution (10 ml) and all tritium-labeled substances can be measured. After addition of 2 ml distilled water 95% of the tritiated water is partitioned in the aqueous phase and only (1 beta,2 beta-3H]-androstendione or [1,2-3H]-androstendione and tritium labeled estrogens can be counted. The amount of tritiated water in each test can be calculated by impulse differences before and after addition of 2 ml distilled water. This aromatase assay using [1,2-3H]-androstendione was compared to a method described by Thompson and Siiteri [1] depending on extraction of steroids prior to scintillation counting. A good agreement of both methods was found. In tests with human term placenta aromatase in microsomes the apparent Km of androstendione was determined to be 8.9 nM. Aminoglutethimide showed a 50% inhibition of the placental microsomal aromatase at 0.6 microM.

Aminoglutethimide↗
PubMed1982

Partial characterization of placental 3 beta-hydroxysteroid dehydrogenase (EC 1.1.1.145), delta 4-5isomerase (EC 5.3.3.1) in human term placental mitochondria.

A partial characterization of human term placental 3 beta-HSDH in mitochondria is reported. Apparent KM of pregnenolone: 70 nM. A dose-dependent stimulation of 3 beta-HSDH by NAD+ or NADP+ was observed in the range from 10(-6) to 10(-3) M (KM value of NAD+: 20 microM). At equimolar concentrations NAD+ is more than 10-fold as effective a cofactor of the 3 beta-HSDH than NADP+. pH optimum: 9.5 (glycine-NaOH buffer). Temperature optimum 40-45 degrees C. A rapid loss of 3 beta-HSDH activity was found after preincubation of the enzyme at 37 degrees C after 30 min; less than 50% of initial enzyme activity is present. No inhibition was obtained by Mg2+, Ca2+ Sr2+ and Ba2+ (1-100 mM). A strong inhibition was achieved with 1 mM Zn2+, Cd2+, Cu2+ and 10 mM and 100 mM Fe2+, Mn2+, Co2+ and Ni2+.

3-Hydroxysteroid Dehydrogenases↗
PubMed1982

Diagnosis of intrauterine fetal growth retardation by prolongation of dehydroepiandrosterone sulfate (DHAS) half-life after DHAS loading.

In the last trimester of pregnancy, a correlation was established between the serum dehydroepiandrosterone sulfate (DHAS) half-life of the mother (n = 40) after DHAS loading (50 mg i.v.) and the birth weight percentile of the newborn. The DHAS half-life in pregnancies with normal fetal growth (greater than 10th percentile) was found to be 3.76 +/- 0.91 h (mean +/- SD) (n = 29) and in pregnancies with small-for-date babies (less than 10th percentile) was assessed to be 6.03 +/- 0.63 h (mean +/- SD) (n = 10) (P less than 0.001). Retrospective diagnosis of an intrauterine fetal growth retardation or normal fetal growth was based on a DHAS halflife threshold of 4.7 h. Retarded fetal growth was detected in all cases (10/10) by prolonged DHAS half-life (greater than r.7 h). Regular fetal growth was diagnosed in 90% of the cases (27/30) by a DHAS half-life of less than 4.7 h. In two out of these 30 pregnancies, an unexpected prolongation of DHAS half-life (greater than 4.7 h) led to the false diagnosis of poor fetal growth. In one patient, no DHAS half-life could be calculated due to a parabolic decline of the DHAS concentration curve. Indications for the DHAS test are diagnosis of an ultrasonographically symmetric intrauterine fetal growth retardation (biparietal and thoracic diameters) in cases with an indefinite gestational age. Furthermore, consistently low urinary excretion was clarified with particular respect to cases of placental sulphatase deficiency.

Birth Weight↗
PubMed1982

The hCG test: an approach to luteal insufficiency.

Corpus luteum insufficiency often constitutes the main cause of infertility. A corpus luteum test system has therefore been added to existing diagnostic methods. Eight days after the midcyclic LH surge 15 women suffering from infertility were administered i.m. injections of varying doses (5,000, 40,000 and 80,000 IU) of hCG. This was followed by multiple radio-immunological determinations of beta-hCG, 17 beta-estradiol, 17-hydroxyprogesterone and progesterone concentrations in peripheral serum over a period of 24 h. An identical test arrangement operating with physiologic saline was used for comparison with 5 primiparae. Beta-hCG concentrations in peripheral blood showed a dose-dependent increase following hCG injections. 17 beta-Estradiol displayed a diurnal concentration pattern. There was no significant difference, however, between the estradiol concentration following placebo or any of the hCG injections. In the case of progesterone and 17-hydroxyprogesterone a significant increase was found following the hCG injections. On the basis of multiple progesterone and 17-hydroxyprogesterone determinations good, moderate and lacking responses to hCG injections were determined. These were accompanied by normal or reduced basal values of progesterone. This fact may have important consequences for future diagnostics and therapy of sterility caused by luteal insufficiency.

Adult↗
PubMed1982

The role of prostaglandins, cyclic nucleotides and tricarboxylic acids in the regulation of the human placental 20 alpha-hydroxysteroid dehydrogenase in vitro.

The in vitro effect of non-steroidal regulators (prostaglandins, cyclic nucleotides and tricarboxylic acids) on the cytoplasmic 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSDH, EC 1.1.1.149) isolated from human early gestational and term placentas was investigated. When prostaglandins (PG) were tested at 100 microM concentrations, an inhibition of the human placental 20 alpha-HSDH by PGE1 (80% inhibition), PGE2 (70%), PGF1 alpha (40%) PGF2 alpha (30%) and 13,14-dihydro-15-keto-PGF2 (PGFM) (20%) was observed. This effect was shown to be dose-dependent. The I50 (concentration at 50% inhibition) was determined for PGE1 and PGE2 to be 11 microM and 38 microM, respectively. No effect on the activity of the 20 alpha-HSDH could be demonstrated for PGI2 and its stable metabolite 6-keto-PGF1 alpha, for the cyclic nucleotides (dbcAMP, dbcGMP) and for the tricarboxylic acids (citrate, ketoglutarate, lactate, malonate, pyruvate and succinate) when added to the incubation at 100 microM concentration. The 20 alpha-HSDH isolated from early gestational and term placentas did not respond differently to the substances tested. These results suggest that prostaglandins can have a direct, dose-dependent effect on the isolated human placental 20 alpha-HSDH without cyclic nucleotides as intermediates and thereby play a role in the regulation of human progesterone synthesis and metabolism during pregnancy and near term.

20-Hydroxysteroid Dehydrogenases↗
PubMed1982

Serum concentrations of FSH, oestradiol, oestrone and androstenedione in normal and obese women.

The normal ranges of the concentrations of follicle stimulating hormone (FSH), oestradiol (E2), oestrone (E1), and androstenedione (A) were established in 257 healthy women. The hormone levels of 84 normal post-menopausal women were compared with those from a group of 46 post-menopausal women with severe obesity (36.3 +/- 15.2 kg over the ideal weight). The increase of the FSH concentrations during the peri- and post-menopause occurs about 4 yr earlier in the obese than in the normal women. There is no significant difference, however, between the E2 levels of the normal and obese women. In the obese women, A (P less than 0.001) and E1 (P less than 0.05) levels are significantly lower than in the normal women. A weight reduction in the obese women had no influence on the concentrations of A and E2, whereas E1 levels tended to increase. FSH levels also increased significantly during weight reduction.

Adult↗
PubMed1982

[Diagnosis of intrauterine growth retardation--comparison of clinical findings, total oestrogen determination from 24-hour urine and ultrasound biometry (distance measurement, biparietal head diameter and thoraco-abdominal transverse diameter) considering the antepartal and subpartal CTG's].

This article presents the results of clinical examination, total oestrogen determination from 24-h urine and ultrasound biometry -- measurement of the biparietal head diameter and the thoraco-abdominal transverse diameter (under routine conditions) -- for diagnosing intrauterine growth retardation (IUGR). In addition, the antepartal and subpartal CTG's are evaluated in cases of foetal retardation of growth "Single determinations" are confronted with so-called "serial examinations (= observation of the course)". Repeated clinical examinations and multiple determinations of the total oestrogen elimination with the 24-h urine did not result in any clear improvement of the detection rates of deficient development of the foetus (discovery rate with clinical examination = 54%, total oestrogen determination = 60%); there was, in fact, a relatively high rate of false-positive diagnosis (false-positive diagnoses on clinical examination = 31%). On the other hand, simple ultrasound biometry (distance measurements) led to the discovery of about 78% of all foetal growth retardations (perc. less than 10), the false-positive diagnoses rate being only 9%. Pathological antepartal CTG's (less than 8 points according to the Meyer-Menck score) were seen in about 27% of the cases with growth retardation -- with, however, an approximately equal rate of pathological CTG's in newborn of "normal weight". The discovery rate of deficient development of the foetus has been increased by combining ultrasound biometry with the total oestrogen determination from the 24-h urine, to 88% (perc. less than 10). The same applies to the combination of ultrasound biometry with the clinical examination (rate of detection: 87%). Up to 77% of all cases with IUGR have been discovered both by combining the clinical examination with the total oestrogen determination or antepartal CTG, as well as by combining total oestrogen determination with antepartal CTG.

Abdomen↗
PubMed1982

Distribution of estrogen and progesterone receptors on primary tumor and lymph nodes in individual patients with breast cancer.

Primary breast cancer tissue and lymph nodes were obtained from 55 patients, Histologically, 34 of these patients had positive and 21 negative lymph nodes. Estrogen receptors (ER) and progesterone receptors (PR) were determined by a dextran-coated charcoal assay. The tumor tissue was ER positive in 58% of the cases and PR positive in 34%. The malignant lymph nodes were ER positive in 56% and PR positive in 24%. ER in 14% and PR in 5% of the benign lymph nodes could be detected. The primary tumor tissue and the corresponding malignant lymph nodes showed an identical ER and PR status, i.e. both tumor sites were receptor positive or both receptor negative, in 68 and 74%, respectively. However, 21% of the patients had receptor-positive tumors but receptor-negative lymph nodes. Receptor-positive lymph nodes in combination with receptor-negative tumors occurred in only 11% for ER and 6% for PR. These data show that receptor-positive malignant lymph nodes mostly display the same receptors status as the corresponding primary tumor, whereas receptor-negative lymph nodes may be combined with receptor-positive tumors.

Breast Neoplasms↗
PubMed1982

Circadian rhythm of serum progesterone levels in human pregnancy and its relation to the rhythm of cortisol.

Progesterone and cortisol were measured in the peripheral blood of pregnant women using radioimmunoassay. Ten women were between 18 and 25 weeks of pregnancy and 10 were between 32 and 38 weeks of pregnancy. Blood for the hormone determinations was drawn at hourly intervals. A significant circadian progesterone rhythm was found with the nadir at 8.00 h and the peak around midnight. The progesterone rhythm showed a significant inverse relation to the cortisol rhythm (tau = 0.310). No difference was detected between the two groups for progesterone rhythm or its inverse relation to the cortisol rhythm.

Circadian Rhythm↗
PubMed1982

Pharmacologically induced changes in human beta-chorionic gonadotropin (beta-hCG) synthesis by human placenta in organ culture.

In organ cultures the regulation of beta-hCG formation in human placentas of early gestation (EG) and at term (T) was analyzed using the following test substances: dibutyryl cAMP (dbcAMP), theophylline, and by two drugs used to treat patients with premature labor, fenoterol hydrobromide and verapamil hydrochloride. The rapid increase in beta-hCG in culture medium beginning at 24-48 h corresponds to morphologic changes (proliferation of the cytotrophoblast). Beta-hCG synthesis of human placenta is related to an adenylate cyclase as could be shown by dose-dependent stimulation by dbcAMP (T) (after 72 h) (controls = 100%): 2 nM = 125%; 70 nM = 200%; 2 microM = 300%. Similar results were obtained using EG. First stimulation by dbcAMP was found after 2 h and may be caused by a release of intracellular beta-CG or by a direct stimulation of beta-hCG synthesis; late effects (after 48-72 h) are suspected to be due to changes in morphologic differentiation of the placenta in organ culture. Theophylline (0.1 and 1 mM) did not influence beta-hCG formation in EG, whereas in T a dose-dependent stimulation could be achieved (controls = 100%): 0.1 mM = 110%; 1 mM = 300%; and 10 mM = 160%. Fenoterol hydrobromide, a tocolytic beta 2-receptor stimulating agent showed a slight (130-160%) beta-hCG stimulation (after 72 h) (EG and T). The stimulatory effect of a high dose (1 microgram/ml) of fenoterol hydrobromide could be due to a stimulation of beta 2 receptors related to an adenylate cyclase. Dose-related changes in beta-hCG in T were found for the calcium antagonist verapamil hydrochloride (controls = 100%): 0.01 microgram/ml = 125% stimulation; 0.33 microgram/ml = 200% stimulation; 10 micrograms/ml = 100%. As indicated by verapamil tests, calcium ions may play a role in the regulation of beta-hCG production.

Bucladesine↗
PubMed1982

Inhibition of human placental progesterone synthesis by aminoglutethimide in vitro.

Aminoglutethimide (AG) is an inhibitor of P-450 linked steroid hydroxylation reactions including the cholesterol side chain cleavage, which is the rate-limiting step by which the synthesis of pregnenolone and also progesterone can be controlled. d,1-AG is a weak inhibitor of the cholesterol side chain cleavage of human term placenta in vitro. The inhibitory potency of AG was greater in tests with mitochondrial preparations than in organ culture tests. The cholesterol side chain cleavage enzyme in mitochondria from a human term placenta showed a 10% residual activity in the presence of 300 microM AG. A 50% inhibition was obtained using 90 microM AG. Due to large unknown quantities of unlabeled cholesterol a Ki for AG could not be determined. In organ culture tests, the progesterone concentration in culture medium of a human term placenta decreased to 50% of control values with rising amounts of AG (3-300 microM) and increased to 60-70% of control values with higher AG concentrations (up to 3 mM). The slow AG-dose dependent decrease of progesterone in the incubation medium of early human pregnancy can be explained by an inhibition of progesterone degradation by means of hydroxylation. The increase of progesterone at higher AG (300-3000 microM) concentrations could be the result of the fact that degradation is inhibited more than progesterone is formed. AG (100 microM) showed no inhibition of mitochondrial 3 beta-hydroxysteroid dehydrogenase and cytoplasmic 20 alpha-hydroxysteroid dehydrogenase, both isolated from a human term placenta.

20-Hydroxysteroid Dehydrogenases↗
PubMed1981

[Aminoglutethimide - a new drug for the after care in breast cancer].

Aminoglutethimide is an inhibitor of various steroid hydroxylation reactions in the adrenal gland, the ovary, the testis and the placenta; furthermore, the extraglandular estrogen synthesis is inhibited by blocking the aromatase in the subcutaneous fatty tissue.

Aminoglutethimide↗