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J Neulen

Publications and source records attributed to J Neulen.

At least 37 records · Page 2Linked to original sources
PubMed1994

[Ovarian hyperstimulation syndrome].

Techniques of assisted fertilization are usually preceded by ovarian stimulation therapies. This implies the risk of development of an ovarian hyperstimulation syndrome (OHS). With this article, clinical relevance, possible pathogenetic mechanisms, diagnosis, therapy and prevention of OHS are discussed. In addition, three patients with severe OHS are presented. Valid parameters for OHS risk assessment are peripheral E2 values as well as number and diameter of follicles. Until now, the mechanisms which lead to severe OHS are unknown, but hCG seems to trigger the development of symptoms, as OHS very rarely occurs without prior hCG application. Symptoms of severe OHS comprise ovarian enlargement, fluid- and electrolyte imbalance, third space fluid accumulation, haemoconcentration and hypercoagulation. Only symptomatic therapy is available. The significance of vascular mediators for the development of OHS is discussed.

Chorionic Gonadotropin↗
PubMed1994

Non-competitive anti-oestrogenic activity of progesterone antagonists in primate models.

We have summarized some of the studies containing basic biological data suggesting potential therapeutic utility of the anti-proliferative activity of antiprogestins on uterine tissues. The non-competitive anti-oestrogenic effects of RU486 were examined using oestradiol-treated ovariectomized monkeys given RU486, progesterone or both. The oestradiol-induced luteinizing hormone surge of control animals was abrogated by progesterone and/or RU486. Secretory transformation by progesterone was inhibited by RU486 co-administration. RU486 alone (1 mg/kg) induced endometrial secretory transformation, but higher doses (5 mg/kg) induced inhibited proliferation and secretory activity. Thus, in the presence of progesterone, RU486 is antagonistic but, in its absence, RU486 exhibits endometrial progestational effects at low doses and an anti-proliferative (anti-oestrogenic) effect at higher doses. These data encourage continued evaluation of RU486 as a potential contraceptive agent acting at the pituitary and/or endometrial level. Our study also demonstrates that after physiological oestradiol replacement therapy, oestradiol receptor concentrations rise dramatically following antiprogestin treatment; this effect was dose-dependent.

Animals↗
PubMed1994

Influence of the developmental stage and the equilibration time on the outcome of ultrarapid cryopreservation of mouse embryos.

Mouse embryos of different developmental stages from 1- to 8-cell inclusive were ultrarapidly frozen in 0.25 ml French straws after various periods of equilibration (1, 3, 5 and 9 min) in freezing-buffer containing 3.5 M dimethylsulphoxide (DMSO), 0.25 M sucrose, and 20% fetal calf serum (FCS) in phosphate buffered saline (PBS). After thawing in a 37 degrees C waterbath and dilution for 5 min in 0.25 M sucrose in PBS/FCS the embryos were cultured in Ham's F10 medium with 10% FCS (37 degrees C, 5% CO2, 95% humidity) for 4-6 days. The rates of expanded and hatching blastocysts were then evaluated and compared to the corresponding rates of non-frozen controls. Thus, for each cleavage stage, the optimal equilibration time was evaluated. It was 1 min for the 1-cell and 8-cell stages (32 and 81% blastocysts, respectively), and 3-5 min for the 2-cell (76 and 73%, respectively) and the 4-cell stage (88 and 87%, respectively). It is concluded that the ultrarapid freezing method described provides satisfactory results for all tested cleavage stages, but not for the 1-cell stage.

Animals↗
PubMed1994

Comparison between prolactin, gonadotrophins and steroid hormones in serum and follicular fluid after stimulation with gonadotrophin-releasing hormone agonists and human menopausal gonadotrophin for an in-vitro fertilization programme.

The inter-relationship between serum and follicular fluid prolactin, oestradiol, progesterone, follicle stimulating hormone (FSH), and luteinizing hormone (LH) in two groups of women was investigated. In group 1, 32 women were treated with gonadotrophin-releasing hormone agonist (GnRH-a) in a long term protocol and subsequently stimulated with human menopausal gonadotrophin (HMG). In group 2, 25 women were simultaneously stimulated with GnRH-a in a short protocol with HMG. Follicular fluid was collected from 54 follicles in group 1 and 47 follicles in group 2. Serum was obtained on the day of human chorionic gonadotrophin (HCG) administration. Serum prolactin and oestradiol concentrations were significantly higher (P < 0.025 and P < 0.01, respectively) in group 1 than in group 2. Serum LH (P < 0.005), FSH (P < 0.01) and progesterone (P < 0.025) were significantly lower in group 1 than in group 2. Follicular fluid prolactin was significantly higher (P < 0.005) in group 1. No differences were found in follicular fluid progesterone and oestradiol. Follicular fluid LH was significantly lower (P < 0.05) in group 1. Serum prolactin correlated positively with oestradiol in both groups (P < 0.005 group 1; P < 0.02 group 2). No significant correlation was found between serum prolactin and LH in group 1. We conclude that prolactin secretion is independent from LH secretion. Hyperprolactinaemia, which is observed in women stimulated with GnRH-a and HMG, is positively associated with increased oestradiol.

Adult↗
PubMed1993

Vascular endothelial growth factor (VEGF) messenger ribonucleic acid (mRNA) expression in luteinized human granulosa cells in vitro.

Vascularization is a prerequisit for corpus luteum formation. Angiogenesis is supposed to be regulated by vascular growth factors. Vascular endothelial growth factor (VEGF) induces specifically endothelial cell proliferation as well as angiogenesis and increases capillary permeability. With this study we demonstrate for the first time the presence of VEGF-mRNA in human luteinized granulosa cells by Northern blot technique. Granulosa cells were obtained from 11 individual patients undergoing ovarian stimulation for in vitro fertilization procedure. Two transcripts of VEGF-mRNA at 3.9Kb and at 4.3Kb could be detected in each case. Specific transcripts were expressed in different amounts. These results indicate that VEGF may promote at least in part vascularization of the human corpus luteum.

Cells, Cultured↗
PubMed1993

Heterogeneity of human prolactin levels in serum during the early postpartum period.

The distribution of molecular forms of prolactin in serum of women during the 1st postpartum week was studied using column chromatography. Serum was analyzed 1, 4 and 7 days postpartum. Using this technique, three molecular forms of prolactin were detected with approximate molecular weights of < or = 100, 48 and 22 kDa; these were termed 'big-big', 'big' and 'little' prolactin, respectively. The relative amount of each form was measured in relation to the total amount of immunoreactive prolactin eluted from the column. Throughout the first postpartum week big-big prolactin represented a minor fraction of the total immunoreactive prolactin in the serum of lactating women: 4.9%, 5.2% and 4.6% on days 1, 4 and 7, respectively. There was a gradual decrease in the higher molecular weight forms of prolactin (big-big plus big prolactin) from the 1st to the 7th postpartum day. This was associated with a significant increase of the little prolactin from 62.8 +/- 7.2% at the 1st postpartum day to 72.6 +/- 6.5% at the 7th day (p < 0.05).

Adult↗
PubMed1992

The role of eicosanoids in reproduction.

The central role of eicosanoids in reproduction was studied in areas of important clinical interest. First, their involvement in pregnancy-induced hypertension was investigated. Urine of normotensive and hypertensive pregnant women was analysed for 6-keto-PGF1 alpha, TXB2 and PGE2 by HPLC/RIA. PGE2 and 6-keto-PGF1 alpha excretion was markedly reduced in the preeclamptic subgroup of hypertensive patients during the last two trimesters. A reduced urinary excretion of 6-keto-PGF1 alpha, TXB2 and PGE2 was also found in a hypertension animal model (rat). Further, tissue cultures of human placentas, deciduas and fetal membranes from hypertensive pregnancies displayed a reduced prostaglandin production. Secondly, in the same in-vitro model the central role of PGE2 of fetal membrane origin for the beginning or parturition was shown. Thirdly, concerning endometrial function, the enhancement of PGF2 alpha and PGE2 formation in secretory endometrial cells by estradiol-17 beta and progesterone was documented. Fourthly, lipoxygenase product content in peritoneal fluid of endometriotic patients did not differ from controls.

Animals↗
PubMed1991

Cell surface-binding sites for progesterone mediate calcium uptake in human sperm.

Recent studies (e.g. Blackmore, P. F., Beebe, S. J., Danforth, D. R., and Alexander, N.) (1990) J. Biol. Chem. 265, 1376-1380) have shown that in human sperm, progesterone produces a rapid increase in intracellular free calcium ([Ca2+]i) and an induction of the acrosome reaction (e.g. Osman, R. A., Andria, M. L., Jones, A. D., and Meizel, S. (1989) Biochem, Biophys. Res. Commun. 160, 828-833). In this study, the location of progesterone receptors on the cell surface of human sperm was identified using progesterone immobilized on bovine serum albumin (BSA) (progesterone 3-(O-carboxymethyl)oxime:BSA) as well as progesterone and its 3-O-carboxymethyloxime derivative. Using fluorescence microscopy, BSA-fluorescein isothiocyanate was shown to be excluded from intact sperm, thus validating the use of progesterone 3-(O-carboxymethyl)oxime:BSA to identify cell surface-binding sites for progesterone. The immobilized progesterone and the 3-O-carboxymethyloxime derivative rapidly increased [Ca2+]i and were full agonists, although they were approximately 1.5 orders of magnitude less potent than progesterone. They also displayed an identical time course to increase [Ca2+]i as free progesterone, and the entire increase in [Ca2+]i was due to the influx of Ca2+. This progesterone-mediated response displayed different steroid receptor characteristics since the very potent inhibitors of genomic progesterone responses, RU38486 and ZK98.299, were very ineffective at inhibiting the progesterone-mediated increase in [Ca2+]i. Also the synthetic progestins megestrol, medroxyprogesterone acetate, norgestrel, norethynodrel, norethindrone, R5020, and cyproterone acetate did not mimic the effects of progesterone to increase [Ca2+]i. It is proposed that a distinct nongenomic cell surface receptor for progesterone exists in human sperm.

Calcium↗
PubMed1991

Arachidonic acid metabolism and prostaglandin production by primate preimplantation blastocysts.

Preimplantation embryos of many species are known to synthesize prostaglandins. These tissue hormones are believed to influence embryonic metabolism, as well as embryo-maternal interaction during implantation although their putative role(s) remains obscure. Here, prostaglandin production by blastocysts from cynomolgus monkeys (Macaca fascicularis) was examined qualitatively during in vitro culture. Tritium labelled arachidonic acid was metabolized to 6 keto-prostaglandin F1 alpha, 2,3-dinor-prostaglandin F1 alpha and thromboxane B2, as characterized by HPLC separation. Also, 6-keto-prostaglandin F1 alpha, and thromboxane B2 as characterized by HPLC separation. Also, 6-keto-prostaglandin F1 alpha and thromboxane B2 were identified by specific RIA's. Our data suggest that the main arachidonic acid metabolites produced by blastocysts of cynomolgus monkeys are prostacyclin and thromboxane.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

RU 486 (mifepristone): induction of dose dependent elevations of estradiol receptor in endometrium from ovariectomized monkeys.

This study was designed to investigate the effect of the anti-progestin RU 486 on estradiol receptor concentrations in the endometrium of monkeys given physiologic estrogen replacement therapy. Estradiol-17 beta (E2) silastic implants were inserted infrascapularly into 12 long-term ovariectomized cynomolgus monkeys (Macaca fascicularis) resulting in an average peripheral serum level of approximately 100 pg/ml estradiol. On day 6 of E2 treatment four treatment groups were initiated: Group I--estradiol implants only; Group II--estradiol implants plus 11 mumol progesterone/kg bodyweight in sesame oil via im injections on days 6,7,8; Group III--estradiol implants plus 2.2 mumol RU 486/kg in sesame oil via im injections on day 6,7,8; Group IV--estradiol implants plus 11 mumol RU 486/kg via im injections on day 6,7,8. On treatment day 9 endometrial biopsies were removed by hysterotomies. Cytosolic and nuclear estradiol receptor contents of tissues were estimated by charcoal method. In Group I, the tissue contained 376 +/- 123 pmol bound H-E2/g protein; the nuclear portion was about 16%. In Group II, the tissue contained 216 +/- 64 pmol bound 3H-E2/g protein; the nuclear portion was only 8%. In Group III, tissue contained 654 +/- 47 pmol bound H-E2/g protein; the nuclear portion was about 22%. In Group IV, the tissue contained 1198 +/- 172 pmol bound 3H-E2/g protein; the nuclear portion was about 17%. Scatchard plot analysis indicated a Kd app of 1.04 x 10(-9) M. This study demonstrates that after physiologic E2 replacement therapy estradiol receptor concentrations rise dramatically following anti-progestin treatment; this effect was dose dependent.

Animals↗
PubMed1989

The effect of cortisol on the synthesis of prostaglandins (PGF2 alpha, PGE2) by human endometrial fibroblasts in vitro with and without addition of estradiol-17 beta or progesterone.

Cortisol is known as a potent inhibitor of phospholipase A2 activity in several tissues. In fibroblast monolayer cell cultures from proliferative human endometrium cortisol alone does not affect the basal PGF2 alpha or PGE2 synthesis. After stimulation of PGF2 alpha production by 10(-7) mol/l estradiol-17 beta increasing concentrations of cortisol up to 10(-5) mol/l dosedependently reduce the PGF2 alpha production. Also the progesterone (10(-4) mol/l) stimulated increase of PGF2 alpha and PGE2 synthesis is inhibited by cortisol (10(-7) mol/l).

Cells, Cultured↗
PubMed1989

The effect of clomiphene on the synthesis of prostaglandins (PGF2 alpha, PGE2, PGI2) in human endometrial cells in vitro with and without addition of estradiol-17 beta or progesterone.

The production of prostaglandin F2 alpha in monolayer stromal cell cultures of proliferative human endometrium is enhanced by 10(-7) mol/l estradiol-17 beta or 10(-4) mol/l progesterone. Progesterone in high concentration (10(-4) mol/l) also enhanced the synthesis of prostaglandin E2. Clomiphene citrate reduced this increased prostaglandin production dose dependently. The synthesis of prostaglandin I2 was not influenced either by sex steroids or by clomiphene citrate.

Cells, Cultured↗
PubMed1989

Effects of progesterone and oestradiol-17 beta on 17 beta-ol-dehydrogenase activity in stromal cells of human endometrium under in-vitro conditions.

A 17 beta-ol-dehydrogenase activity could be demonstrated in fibroblast monolayer cell cultures of proliferative human endometrium. After 24 h incubation 100 nCi [6,7-3H]oestradiol-17 beta was completely oxidized to oestrone. Progesterone was not able to enhance the metabolizing velocity. In contrast, progesterone incubation revealed a decreasing oxidation rate with increasing molarity. Histological changes after transformation of the endometrium are discussed to explain in-vivo results showing an increased 17 beta-ol-dehydrogenase activity in the secretory phase of the cycle.

17-Hydroxysteroid Dehydrogenases↗
PubMed1988

[Effects of sex steroids on the lipoprotein profile].

Plasma testosterone levels were measured pre- and postoperatively as well as during estrogen substitution in a 47-year-old woman with excessive hyperandrogenaemia due to a Leydig-cell tumour of the left ovary. In addition, the lipoprotein profile was determined before and 14 days after removal of the tumour and four weeks later during estrogen substitution. The preoperative plasma testosterone level was between 6.25 and 8.50 ng/ml; at the same time there was a hypercholesterolaemia with increased beta-lipoprotein and decreased alpha-lipoprotein fractions: the ratio of beta- to alpha-lipoprotein cholesterol was 3.0, a type IIa hyperlipoproteinaemia. After the testosterone concentration had returned to normal both the beta- and pre-beta cholesterol fell significantly, while the alpha-lipoprotein fraction remained unaltered. The alpha-cholesterol fraction increased significantly after estrogen substitution, the beta- to alpha-lipoprotein ratio being 1.20. It is concluded from these results that hyperandrogenaemia goes together with raised peripheral beta and pre-beta-cholesterol concentration, while estrogens cause a rise in the alpha-fraction.

Cholesterol↗
PubMed1988

Effects of estradiol-17 beta and progesterone on the synthesis of prostaglandin F2 alpha, prostaglandin E2 and prostaglandin I2 by fibroblasts from human endometrium in vitro.

Estradiol-17 beta increases the production of prostaglandin F2 alpha (PGF2 alpha) in long term monolayer cell cultures of the human endometrium in a dose dependent manner. Progesterone in pharmacological dosage stimulates the syntheses of PGF2 alpha and of prostaglandin E2 (PGE2). The synthesis of prostaglandin I2 (PGI2) is not influenced by sex steroids in long term monolayer cell cultures of the human endometrium.

Dinoprost↗