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Biomedical subjects

L Kiesel

Publications and source records attributed to L Kiesel.

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

Stimulation of luteinizing hormone release and cyclic nucleotide production by arachidonic acid in cultured pituitary gonadotrophs.

Gonadotropin-releasing hormone (GnRH) stimulates luteinizing hormone (LH) release and cyclic guanosine 3',5-cyclic monophosphate (cGMP) production in rat anterior pituitary cells through a calcium-dependent activation mechanism that involves increased phospholipid turnover and liberation of arachidonic acid. In enriched pituitary gonadotrophs, LH release was stimulated by arachidonic acid and its oxygenated metabolite, 5-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE), in a dose-dependent manner. The prominent LH responses of purified gonadotrophs to arachidonic acid suggest that the secretory actions of arachidonate are exerted primarily on the gonadotroph and do not involve the participation of other pituitary cell types. Preincubation of pituitary cells with stimulatory concentrations of arachidonic acid for up to 120 min did not alter the subsequent LH responses elicited by GnRH, indicating that the secretory mechanism was unimpaired by arachidonate treatment and that no cross-desensitization occurs during sequential exposure of gonadotrophs to the two stimuli of LH release. Cyclic adenosine 3',5-monophosphate (cAMP) production was stimulated by 10 microM arachidonic acid to the same degree (about 2-fold) as by GnRH, but did not parallel the progressive LH response to higher arachidonate concentrations. cGMP production was initially stimulated by addition of arachidonic acid but returned to the control value after 5 min, whereas GnRH typically elicited a prolonged cGMP response. In contrast to the calcium-independent action of arachidonic acid, the stimulatory effect of 5-HETE on LH release required the presence of extracellular Ca2+, as previously observed for GnRH. These findings demonstrate that arachidonic acid and its metabolite, 5-HETE, partially reproduce the actions of GnRH upon LH release and cyclic nucleotide production.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
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↗
PubMed1986

Top concentrations of dynorphin-like immunoreactivity in fractions of rat anterior pituitary cells enriched in gonadotrophs.

A possible relationship between anterior pituitary cells containing luteinizing hormone (LH) and those containing the endogenous opioid dynorphin and other proenkephalin B-derived peptides was examined. Gonadotroph-enriched and gonadotroph-depleted cell fractions were prepared from cell suspensions of adult female rat anterior pituitary glands by centrifugal elutriation. Fractions with high or low concentrations of LH contained also high or low concentrations of dynorphin-like immunoreactivity. A positive correlation was found between the content in the eluted cell fractions of LH and dynorphin-like immunoreactivity with a correlation coefficient and a slope of the regression line close to one. Therefore, LH-containing and dynorphin-containing cells of the rat adenohypophysis exhibit almost the same characteristics under the conditions of centrifugal elutriation. This is consistent with the suggestion that dynorphin and other proenkephalin B-derived peptides may be colocalized with LH and/or follicle-stimulating hormone in at least some of the gonadotrophs of the rat anterior pituitary gland.

Animals↗
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↗
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

Mechanism of action of gonadotropin releasing hormone: role of lipoxygenase products of arachidonic acid in luteinizing hormone release.

The mechanism of action of gonadotropin-releasing hormone (GnRH) upon pituitary luteinizing hormone (LH) secretion has not yet been elucidated, but recent evidence has suggested that arachidonic acid or its metabolites are involved in GnRH action. In cultured rat pituitary cells, arachidonic acid and 5-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE) elicited concentration-dependent release of LH with EC50 of about 12 microM. Other lipoxygenase derivatives including 11-, 12- and 15-HETE, had no consistent effect on LH release, and leukotrienes (B4 and C4) exerted only minor stimulatory actions on LH release. The lipoxygenase inhibitors nordihydroguaiaretic acid (NDGA), 5,8,11,14-eicosatetraynoic acid (ETYA), and 3-amino-1-(3-trifluoromethyl phenyl)-2-pyrazoline hydrochloride (BW 755C) caused dose-dependent inhibition of GnRH-induced LH release, with IC50 values of 5, 8.5, and 175 microM, respectively. In contrast, the cyclooxygenase inhibitor, indomethacin, had a biphasic action on GnRH-stimulated LH release, with potentiation of GnRH action at low doses (up to 25 microM) and no effect at higher concentrations. These findings are consistent with the potential role of a 5-lipoxygenase product of arachidonic acid in the mechanism of action of GnRH on pituitary gonadotropin release.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
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↗
PubMed1985

[Therapy of testicular tumors in childhood].

Between 1954 and 1984 41 primary testicular tumours were treated in 40 children at the age of 0 to 9 years as well as 9 secondary testicular tumours in malignant systemic diseases or metastases. The histological reclassification of the number of cases revealed 15 yolk-sac-tumours, 10 differentiated teratomas of immature subtype, 1 intermediary malignant teratoma, 3 undifferentiated malignant teratomas, 2 Sertoli-cell-tumours (1 double-sided) and 5 rhabdomyosarcomas. 2 children each with undifferentiated malignant teratomas and rhabdomyosarcomas died, all before 1970. 5 children with yolk-sac-tumours and 2 with rhabdomyosarcomas who since 1974 have been treated with Ablatio testis and combination chemotherapy live without tumour. Histological classification and division into stages are proved and form the basis of a therapy conception which in all testicular tumours apart from the Ablatio testis contains the chemotherapy of different intensity (HTK-84), taking into consideration form of tumour, stage and age of the children. The retroperitoneal lymphadenectomy is recommended only in the proof of metastases.

Adolescent↗
PubMed1984

Phosphatidic acid and the calcium-dependent actions of gonadotropin-releasing hormone in pituitary gonadotrophs.

The stimulation of luteinizing hormone (LH) release and cyclic GMP (cGMP) production in rat anterior pituitary cells by gonadotropin-releasing hormone (GnRH) are receptor mediated and calcium dependent, and have been shown to be accompanied by increased phospholipid turnover and arachidonic acid release. The incorporation of 32Pi into the total phospholipid fraction of pituitary gonadotrophs was significantly elevated by 10(-8) M GnRH, with specific increases in the labeling of phosphatidylinositol and phosphatidic acid (PA). Since PA acts as a calcium ionophore in several cell types, its effects upon calcium-mediated gonadotroph responses were compared with those elicited by GnRH. In rat pituitary gonadotrophs prepared by centrifugal elutriation, PA stimulated LH release and cGMP production by 9-fold and 5-fold, respectively. The stimulation of LH release by 30 microM PA was biphasic in its dependence on extracellular calcium concentration, rising from zero in the absence of calcium to a maximum of 10-fold at 0.5 mM Ca2+ and declining at higher calcium concentrations. In dose-response experiments, PA was 3-fold more potent at 0.5 mM Ca2+ than at 1.2 mM Ca2+. The cGMP response to PA in cultured gonadotrophs was also calcium dependent, and was progressively enhanced by increasing Ca2+ concentrations up to 1.5 mM. The ability of PA to stimulate both LH release and cGMP formation in a calcium-dependent manner suggests that endogenous PA formed in response to GnRH receptor activation could function as a Ca2+ ionophore in pituitary gonadotrophs, and may participate in the stimulation of gonadotroph responses by GnRH and its agonist analogs.

Animals↗
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

Arachidonic acid metabolism in gonadotroph-enriched pituitary cells.

Control of pituitary hormone secretion by hypothalamic-releasing peptides appears to involve unidentified products of the cyclooxygenase and lipoxygenase pathways, as well as the adenylate cyclase system. To identify the patterns of arachidonic acid metabolism in specific pituitary cell types, the labeled products formed from [14C]-arachidonic acid were analyzed in rat pituitary cells separated by centrifugal elutriation into fractions enriched in gonadotrophs, somatotrophs and lactotrophs. Gonadotroph-enriched cell fractions metabolized arachidonic acid to 11-, 12- and 15-HETE, HHT, PGD2, PGE2 and TXB2. The products were characterized by high performance liquid and thin-layer chromatography, together with gas chromatographic-mass spectrometric identification of 12- and 15-HETE. In cells preincubated with indomethacin, the formation of 11-HETE, HHT, PGD2, PGE2 and TXB2 was markedly reduced. In gonadotroph-enriched cell fractions, the production of cyclooxygenase metabolites was 3 to 4 times greater than that of lipoxygenase products. The somatotroph- and lactotroph-enriched cell fractions produced only very small amounts of oxygenated arachidonic acid metabolites under the conditions studied, but all cell fractions incorporated [14C]-arachidonate into mono-, di- and tri-glycerides, as well as into phospholipids. These results demonstrate the differential capacities of the individual pituitary cell populations for metabolizing arachidonic acid, and emphasize the relative prominence of the oxidation pathways for arachidonate metabolism in the gonadotroph-enriched cell fraction of the rat pituitary gland.

Animals↗