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Biomedical subjects

T Rabe

Publications and source records attributed to T Rabe.

At least 91 records · Page 5Linked to original sources
PubMed1987

Leukotrienes stimulate gonadotropin release in vitro.

Monolayer cell cultures of female rat anterior pituitaries were used to investigate the effect of leukotrienes (LT) LTA4, LTB4, LTC4, LTD4, LTE4 and other lipoxygenase metabolites of arachidonic acid (5-HETE, 5-HPETE, and 15-HETE) in vitro. 3H-arachidonic acid was rapidly incorporated into pituicytes and its release was enhanced by gonadotropin releasing hormone (GnRH) in superfused pituitary cells. Leukotrienes were found to be very potent stimulators of the release of luteinizing hormone (LH) when added as pulses to superfused pituicytes. At equimolar concentrations, LTA4, LTB4, LTC4 and LTE4 were found to be more potent than the physiological stimulus GnRH. LTD4 did not affect gonadotropin secretion. Other lipoxygenase metabolites of arachidonic acid, such as 5-HETE, 5-HPETE and 15-HETE were less effective on the exocytosis of LH. These results suggest that leukotrienes are potential mediators of GnRH action on gonadotropin secretion and are possible sites of regulation of pituitary function.

Animals↗
PubMed1987

Clinical and metabolic effects of gestodene and levonorgestrel.

The new low-dose combination oral contraceptive (OC) containing 75 micrograms of the new progestogen gestodene (GTD) plus 30 micrograms ethinyl estradiol (EE) was clinically tested and compared with a levonorgestrel (LNG) combined pill (150 micrograms LNG plus 30 micrograms EE). In a randomized clinical comparative study (A), 176 women were treated with the GTD-containing pill and 185 with the LNG-containing pill for six cycles. This study was followed by a second multicenter study (B) covering 707 patients taking the GTD-containing pill for up to 24 cycles (total, 9,947 cycles). In a third study (C), metabolic effects were assessed using a randomly organized baseline control trial (pretreatment/treatment cycles); 30 patients received the GTD-containing pill and 30 received the LNG-containing pill. Carbohydrate metabolism, lipid metabolism, and blood clotting were investigated, and an interim analysis was performed after six OC cycles. No pregnancies and no severe side effects occurred in any of the studies. Intermenstrual bleeding decreased as usual during treatment. In the total number of gestodene cycles in studies A and B, there was a 6.9% incidence of spotting, a 0.8% incidence of breakthrough bleeding, and a 0.7% incidence of both spotting and breakthrough bleeding in studies A and B patients taking gestodene. Amenorrhea occurred in 0.6% of cycles. Body weight remained unchanged (+/- 2 kg) after 24 cycles in 80.5% of study B patients taking gestodene. Blood pressure remained normal in about 95% of all study B patients; a normalization was observed in greater than 60% of patients with previously elevated blood pressure. No clinically relevant changes in carbohydrate metabolism, lipid metabolism, or blood clotting were observed in study C. The new GTD-containing low-dose combination pill proved to be a safe and reliable contraceptive agent.

Adolescent↗
PubMed1986

Gonadotropin releasing hormone enhances polyphosphoinositide hydrolysis in rat pituitary cells.

Addition of gonadotropin releasing hormone to myo-[2-3H]inositol-prelabeled rat pituitary cells in primary culture evoked a dose-dependent increase of the accumulation of [3H]inositol phosphates with a rise of inositol triphosphate within 30 sec of stimulation, followed by a rise in inositol diphosphate and inositol monophosphate. Inositol phosphate accumulation was enhanced up to 5-to-8-fold and was time-dependent between up to 15 min incubation without further increase beyond this time period. Without preincubation with LiCl2, there was no measurable increase of GnRH-induced inositol phosphate accumulation compared to controls. The presence of calcium in the incubation medium did not affect the increase of inositol phosphates. These data give evidence, that polyphosphoinositide breakdown may be an early step in the action of gonadotropin releasing hormone on gonadotropin secretion.

Animals↗
PubMed1986

Diagnosis of intrauterine fetal growth retardation by DHAS half-life.

A DHAS test (50 mg i.v.) was performed on 49 women with clinically suspected intrauterine fetal growth retardation (IUGR) in the last trimester of pregnancy. A correlation could be established between the serum DHAS halflife (DHAS-T 1/2) of the mother after DHAS loading and the birthweight percentile of the newborns, which were retrospectively divided into two groups; one with regular intrauterine fetal growth (birthweight greater than 10th percentile) (n = 28) and one with poor intrauterine fetal growth (IUGR) (less than 10th percentile) (n = 21). The DHAS loading test was retrospectively evaluated by the correct diagnosis of intrauterine fetal growth; a DHAS halflife below 4.7 h was taken as a threshold for normal intrauterine fetal growth as indicated by a previous study by our group: DHAS-T 1/2 (less than 10th birthweight percentile): 6.00 +/- 1.43 h (mean +/- S.D.) (n = 18), DHAS-T 1/2 (greater than 10th birthweight percentile): 4.37 +/- 1.06 h (mean +/- S.D.) (n = 28). In 89% (16/18) of the cases (less than 10th birthweight percentile), a prolonged DHAS-T 1/2 (greater than 4.7 h) led to the correct diagnosis of an IUGR. In 75% (21/28) of the cases with regular fetal growth, a DHAS-T 1/2 of less than 4.7 h could be registered. In three cases with intrauterine death of the fetus, a prolonged DHAS-T 1/2 of 7.64 +/- 0.37 h (mean +/- S.D.) was found. Furthermore, IUGR could not be detected in three cases by DHAS loading (DHAS-T 1/2 3.77 +/- 0.51 h (mean +/- S.D.) due to betamethasone induction of lung maturation prior to the DHAS test. Indications for the DHAS test include the diagnosis of an ultrasonographically symmetric IUGR (biparietal and thoracic diameters) in cases with an indefinite gestational age and the detection of a placental sulfatase deficiency by means of a delayed conversion of DHAS to dehydroepiandrosterone.

Birth Weight↗
PubMed1986

[Light and electron microscopy changes in the endometrium caused by the administration of a norgestimate-containing oral contraceptive (Cilest)].

Endometrium morphology has been analysed by means of light microscopy, scanning and transmission microscopy in patients before and during treatment with a norgestimate containing low dose combined pill (Cilest). Endometrium biopsies were taken after 1 (N = 3), 2 (N = 3), 3 (N = 7), 5 (N = 1) and 6 (N = 4) OC cycles. Light microscopy of the endometrium obtained during the OC-free pretreatment cycles shows a regular secretory transformed endometrium. During the first OC cycles of Cilest treatment slight growth retardation of endometrial glands was observed. Endometrium after 3 to 6 OC cycles showed an increasing delay of the growth of endometrial glands in terms of an abortive secretion. Morphometric studies revealed a retardation of the development of endometrial glands and an "arrest of secretion". The degree of proliferation varied slightly; a general delay between the date of the menstrual cycle and endometrial dating was evident. Using scanning electron microscopy the endometrium presented mostly a regular surface corresponding to the midcycle or a late proliferative phase up to the early secretory phase. Infiltrative dysplasia or inflammatory changes as well as local proliferations could not be detected. In transmission electron microscopy with semi-thin and ultrathin slices, stroma, structure of glands and surface appeared to be normal. Furthermore, no time delay between the endometrium and the day of menstrual cycle was observed. During treatment with a norgestimate containing low dose combined pill, only slight changes of the endometrium in terms of a growth retardation of endometrial glands were seen in the first 6 treatment cycles.(ABSTRACT TRUNCATED AT 250 WORDS)

Contraceptives, Oral, Combined↗
PubMed1986

The role of novel arachidonic acid metabolites in GnRH action on gonadotrophin release in vitro.

Lipoxygenase metabolites of arachidonic acid were shown to stimulate gonadotrophin release dose-dependently in rat pituitary cells. The secretory activity of the arachidonate metabolite leukotriene C4 (LTC4) was biphasic and 10-fold more potent than that of the physiological stimulus gonadotrophin-releasing hormone (GnRH). In pre-labelled, superfused pituitary cells, GnRH dose-dependently enhanced the release of [3H]arachidonic acid, which occurred simultaneously with the secretion of luteinizing hormone (LH). When cells were pre-treated with GnRH for 24 h no response to a further stimulus by GnRH (10(-7) M) could be observed for either [3H]arachidonate nor LH, demonstrating that also in desensitized cells these two mechanisms react similarly. In addition, a GnRH antagonist did not affect the release of arachidonate or LH. These results suggest that arachidonic acid may be involved in the mechanism of GnRH action on gonadotrophins via its lipoxygenase metabolites and LTC4 could act as a very potent intracellular stimulus of LH secretion.

Animals↗
PubMed1986

Progestins and carbohydrate metabolism.

The effect of hormonal oral contraceptives (OCs) on carbohydrate metabolism depends on the amount of estrogen (ethinyl estradiol or mestranol), type and amount of progestin, formulation of the pill (monophasic, sequential, or triphasic), duration of use, mode of administration (oral v parenteral), and race and genetic predisposition of the user. The progestin megestrol has minimal effect on carbohydrate metabolism but is no longer available due to its carcinogenic effects in beagle dogs. Combination pills with norethindrone and its derivatives (norethindrone acetate, norethynodrel, and ethynodiol diacetate) show moderate impairment of glucose tolerance with definite hyperinsulinemia. The lowest metabolic effect was observed with triphasic formulations. The effect of levonorgestrel depends on the formulation; the highest impairment of glucose and insulin response after oral glucose loading is found in sequential and combined formulations with doses of 50 micrograms ethinyl estradiol, whereas with doses of 30 micrograms ethinyl estradiol only minor effects on glucose tolerance are seen. Few effects were observed while using triphasic preparations. Therefore, to minimize disturbances of carbohydrate metabolism, low-dose formulations and triphasic preparations should be used.

Carbohydrate Metabolism↗
PubMed1986

Lipid, carbohydrate, and androgen metabolism in women using a triphasic oral contraceptive containing norethindrone for one year.

A clinical trial was conducted to determine the effects of a norethindrone-containing triphasic oral contraceptive, Ortho-Novum 7/7/7, on lipid, carbohydrate, and androgen metabolism in 22 women during 12 cycles of use. Examinations were made in two consecutive cycles before treatment and after 3, 6, 9, and 12 cycles of treatment. Treatment consisted of ethinyl estradiol, 35 micrograms/d for 21 days, together with norethindrone in stepwise-increasing doses of 0.5, 0.75, and 1.0 mg/d, with each dose given for seven days. Only a minimal impact on lipid metabolism was observed during treatment. There were no unfavorable changes in any HDL-related measurement. HDL-cholesterol and alpha levels were not altered in any cycle. The HDL:LDL ratio was not significantly altered during treatment. LDL cholesterol levels were also unaltered during treatment, but there were slight elevations in other LDL-related measurements in some cycles. Total cholesterol, phospholipid, and triglyceride levels were elevated in cycle 9, and triglyceride levels also increased in cycle 3, but no significant changes were observed in these levels at any other sampling times. Carbohydrate metabolism did not change significantly as indicated by mean fasting levels of glucose, insulin, and HbA1c or by levels of these parameters after a glucose load. Changes observed in androgenic parameters indicate the lack of androgenicity. The results of this study demonstrate that Ortho-Novum 7/7/7 use results in a minimal impact on lipid metabolism, no change in carbohydrate metabolism, and no potential for androgenic side effects.

Adult↗
PubMed1985

Study of 16,16'-dimethyl-trans-delta 2 prostaglandin E1 methyl ester vaginal suppository for cervical dilatation in premenopausal and postmenopausal women.

In a double-blind placebo-controlled comparative study, 180 female patients were randomly assigned to groups and treated approximately 3 h before dilatation and curettage with either a single 1 mg vaginal suppository of Gemeprost or a matching placebo. The patient population included premenopausal non-pregnant or postmenopausal patients presenting at four participating centers in West Germany. Patients were monitored from the time of drug administration to approximately 24 h after the operation. A marked response to treatment with Gemeprost was noted at the general cervical assessment performed immediately prior to dilatation. A significant increase in diameter of the cervical canal was observed and subsequent mechanical dilatation was found to be significantly easier as a result of Gemeprost treatment. No differences between the response to treatment in premenopausal and postmenopausal patients were found in our interim analysis of 113 patients. The incidence of preoperative uterine pain increased with time as a result of Gemeprost treatment but it was predominantly mild and no analgesics were required. Gastrointestinal side-effects were rare and well tolerated in both treatment groups. This study indicates that Gemeprost is an effective, well tolerated preoperative cervical dilator/softener in non-pregnant patients.

16,16-Dimethylprostaglandin E2↗
PubMed1985

Regulation of human placental progesterone synthesis in vitro by naturally occurring steroids.

A regulatory model of human placental progesterone synthesis is based on studies with isolated placental enzymes. Steroids causing a dose-dependent inhibition are listed in the standing order of their inhibitory potency (I50 (microM)/Ki value (microM)/type of inhibition: c = competitive and nc = non competitive). Cholesterol side chain cleavage enzyme (mitochondria): Mainly regulated by hydroxylated cholesterol derivates. No inhibition was observed by cholesterylesters and by other naturally occurring steroids tested. 5-ene-3 beta-hydroxysteroid dehydrogenase-isomerase (mitochondria): 6 beta-hydroxyprogesterone (nc), dehydroepiandrosterone (0.32/0.82/c), 20 alpha-dihydroprogesterone (0.38/-/nc), progesterone (0.46/-), estrone (0.56/0.1/c), estradiol (0.1/0.8/c), 17 alpha-hydroxyprogesterone (2.1/-/nc), 17 alpha-hydroxypregnenolone (0.4/-/c), dehydroepiandrosterone sulfate (2.5/-/c), cortisone (5.0/-), cortisol (100/-). 20 alpha-hydroxysteroid dehydrogenase (cytoplasmic): estrone (0.26/0.7/c), estradiol (0.28/0.9/c), pregnenolone (4.4/9.2/c), 5 alpha-pregnan-3 beta-ol-20-one (4.6/-/nc), estriol (5.1/11.5/c); dehydroepiandrosterone (7.2/14.0/c), 5 alpha-dihydrotestosterone (26.0/-/nc), progesterone (33.0/48.0/c), dehydroepiandrosterone sulfate (50.0/23.0/nc), and testosterone (59.0/63.0/c). An autoregulatory mechanism of placental progesterone synthesis is postulated which is in good agreement with data published by others proving that placental progesterone synthesis is independent of the endocrine organs of the mother and the fetus.

20-Hydroxysteroid Dehydrogenases↗
PubMed1985

[Use of a new vaginal suppository: prostaglandin E1 analog Gemeprost for cervix maturation prior to abortion in the 1st trimester].

This double-blind study is concerned with the efficacy and safety of a new prostaglandin E1-analogue (16,16'-dimethyl-trans-delta 2PGE1-methylester) (Gemeprost) (ONO-802), which was administered as a single 1 mg vaginal pessary three hours prior to legal abortion. The efficacy of the prostaglandin was assessed by the largest size of the dilator meeting no resistance when inserted in the cervical channel. Furthermore, the quality of the cervix and the effort needed for further dilatation was evaluated. The average size of the cervix prior to dilatation was found to be 10 mm, in comparison to only 7 mm in the placebo-group (p less than 0.001). 80% of the patients of the Gemeprost group did not need any further dilatation, i.e. the dilatation procedure of the cervix was easier than in the group without treatment (19%). The incidence of uterine pain was more frequent in the Gemeprost group (40%) than in the Placebo group (7%). Analgesics were not required. The frequency of gastrointestinal side effects was rare in the Gemeprost group (13%) and in the Placebo group (11%) compared with other prostaglandins. By the preoperative application of a new prostaglandin E1-analogue (1 mg) prior to vacuum aspiration in the first trimenon of pregnancy sufficient softening of the cervix and a dilatation of the cervix was achieved. It significantly reduces the need for further mechanical dilatation of the cervix as well as the force needed to perform this dilatation. These effects reduce the trauma associated with mechanical dilatation and therefore diminish the risk of subsequent complications.

Abortifacient Agents↗
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

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↗