OBJECTIVE: The addition of progestogen to estrogen replacement therapy is thought to antagonize, at least in part, the beneficial effects of estrogens on the vasculature. The aim of this study was to investigate the effect of two progestogens mostly used in clinical practice on the proliferation of vascular smooth muscle cells, which has been demonstrated to be a crucial step in the development of atherosclerosis. MATERIAL AND METHODS: The effect of medroxyprogesterone acetate (MPA) and norethisterone (NET), which represent the two different classes of C21- and C19-progestogens, respectively, was investigated on proliferation of smooth muscle cells from human coronary artery in vitro. The steroids were tested in the concentration range 10(-8) to 10(-5) M, which is in the upper range of that reached during hormonal replacement therapy, and compared with control values. RESULTS: Estradiol significantly inhibited serum-stimulated cell growth at the concentrations 10(-6) and 10(-5) M by 18% and 34%, respectively. MPA significantly enhanced serum-stimulated growth at the concentrations 10(-6) and 10(-5) M by 29% and 47%, respectively. In equimolar combinations of MPA and estradiol, proliferation of the cells was significantly stimulated at the concentrations 10(-6) and 10(-5) M by 26% and 44%, respectively. In contrast, NET had no significant effect on serum-stimulated cell growth and had no impact on the estradiol-inhibited proliferation. CONCLUSIONS: These data suggest that MPA may antagonize beneficial antiatherosclerotic estradiol effects on the vasculature, whereas NET may be neutral in this respect. However, these effects occurred at supraphysiological concentrations. Because these concentrations might be reached in the target tissues, the clinical relevance for treatment of patients with cardiovascular risk cannot be excluded.

Blood↗

PubMedDate not supplied

Effect of an estrogen/statin combination on biochemical markers of endothelial function in human coronary artery cell cultures.

OBJECTIVE: The combination of an estrogen with a statin for therapy of postmenopausal women is of interest because both substance classes exert beneficial effects on the lipid profile. However, both substance classes also elicit positive direct effects on the vasculature. Therefore in the present in vitro study an estrogen/statin combination was investigated for its effect on biochemical markers of endothelial function. MATERIAL AND METHODS: In endothelial cell cultures from human coronary arteries, the effect of estradiol/fluvastatin, alone and in equimolar combinations, were tested at the concentrations 0.01, 0.1, and 1 microM. The vasodilator prostacyclin, the vasoconstrictor endothelin, endothelial nitric oxide synthase (responsible for synthesis of the vasodilator nitric oxide), the procoagulatory factor plasminogen activator inhibitor-1, and the monocyte chemoattractant protein were chosen as markers. RESULTS: The estradiol/fluvastatin combination was able to increase prostacyclin production (25-100%) in an additive manner. The reduction of endothelin synthesis in the range of 21-46% was higher with the combination than with the monosubstances; the reduction, however, was not statistically significant. The expression of endothelial nitric oxide synthase was not significantly increased by the combination compared with the monosubstances, however, a tendency to an additive increase was observed. For the synthesis of plasminogen activator inhibitor-1, no significant changes were seen for either the monosubstances or the combination. The synthesis of monocyte chemoattractant protein-1 was decreased by the combination between 21% and 40%; the decrease, however, was not statistically significant compared with the effect of the monosubstances. The effective estradiol concentrations are higher than can be achieved by replacement therapy; in contrast, fluvastatin was effective at concentrations that can be reached during clinical treatment. CONCLUSIONS: These results indicate that an estrogen/statin combination exerts beneficial effects on the vasculature that seem to be superior to the effects of the monosubstances. The changes found for the biochemical markers can improve endothelial function. The presented results should encourage the performance of clinical studies in cardiovascular risk patients with estrogen/statin combinations.

Anticholesteremic Agents↗

PubMedDate not supplied

Release of anti-PAF activity from PAF-binding human ovarian cancer cells in culture.

The human ovarian cancer cell line EFO-27 in culture spontaneously produced anti-PAF activity, which eluted from HPLC in the range of synthetic PAF. The activity therefore appears to be due to an antagonistic PAF-analogue. It was detected by a suppressed PAF-induced platelet aggregation in vitro. EFO-27 cells were found to be able to bind synthetic PAF with saturable binding kinetics. This binding led to reduced cell proliferation. The production of anti-PAF activity by EFO-27 cells resembles an autocrine growth regulation in the light of recent findings that other malignant transformed cell lines produce PAF-like activity in vitro if stimulated appropriately.

Cell Division↗

PubMedDate not supplied

Immunoreactive relaxin in seminal plasma of man.

Relaxin in seminal fluid was determined radioimmunologically in 238 andrological patients with various ejaculate qualities. In 52 cases, a second ejaculate was examined 4 to 6 weeks later. Relaxin was found present in each ejaculate sample. There was no significant difference between the relaxin values of the reexamined cases and the original samples, indicating little fluctuation. Statistical correlations between relaxin levels in seminal plasma and clinical data, ejaculate, and hormonal parameters could not be established. Only cases with low fructose values showed some correlation with low relaxin levels in seminal plasma.

Adult↗

PubMedDate not supplied

Immunoreactive ubiquitin in human seminal plasma.

The polypeptide ubiquitin, up to now almost exclusively discovered in intracellular spaces, was measured immunologically in a total of 187 samples of human seminal plasma. The values were between 1.83 and 19.11 micrograms/ml. In spermatozoa ubiquitin was detected too; the values, however, were significantly lower than in the seminal plasma. The origin and function of ubiquitin in human seminal plasma is still unclear. The possible role of ubiquitin in reproduction is discussed.

Animals↗

PubMedDate not supplied

[Relaxin in amniotic fluid and serum of pregnant patients].

Relaxin was measured in serum and amniotic fluid of 136 pregnant women between the 12th and 38th gestational week by means of a new human relaxin-RIA. The pregnancies consisted of 111 pathology-free single fetuses, 10 with rhesus incompatibility, 7 with chromosomal aberration and 8 with sonographic diagnosed abnormalities. Relaxin could be detected in all samples tested the levels being ten times lower in amniotic fluid compared to serum. Serum relaxin levels showed a slight but not statistically significant decrease with increasing gestational age, in amniotic fluid relaxin values were consistent over the course of pregnancy. The ratio of amniotic fluid to serum relaxin displayed a statistically significant increase from the 12th to 23rd week of pregnancy. Individual courses of relaxin concentration in amniotic fluid revealed only low intra-individual variations but distinct inter-individual differences.

Adult↗

PubMedDate not supplied

Estradiol concentrations in premenopausal women with coronary heart disease.

BACKGROUND: Because of the beneficial effects of estrogen, premenopausal women are normally protected against coronary heart disease (CHD) and are at lower risk for myocardial infarction; consequently, CHD occurs very rarely in menstrually active women. Given this background, the aim of the present study was to test the hypothesis that decreased concentrations of estrogen are associated with CHD in premenopausal women. METHODS: Fourteen premenopausal women with CHD were investigated and compared with a healthy control group comparable for age and cardiovascular risk factors. Relevant characteristics of patients and controls were assessed: age, blood pressure, body mass index, total cholesterol and high-density lipoprotein cholesterol, triglycerides, former pregnancies, ovariectomy and related surgical interventions, smoking history and former use of oral contraceptives. To ensure the premenopausal status of the participants, the regularity of the menstrual cycle and the follicle-stimulating hormone concentrations were also assessed. Plasma estradiol and progesterone and urine estrone concentrations (24 h urine collection) were measured at day 6 after estimated ovulation to assess the relative increase in plasma estradiol and progesterone during the second half of the menstrual cycle. RESULTS: Compared with the control group, premenopausal women with CHD had significantly lower concentrations of plasma estradiol (408.9 +/- 141 pmol/l and 287.8 +/- 109 pmol/l respectively; P = 0.0228) and total estrogen (2061 +/- 693 pg/mumol creatinine and 1607 +/- 448 pg/mumol creatinine respectively; P = 0.025) in the urine. However, the progesterone concentrations were not significantly different between the groups. These findings might be explained by a partial ovarian dysfunction, as the patient group had a significantly higher number of tubal sterilizations (eight compared with one). CONCLUSION: Our data provide support for the hypothesis that decreased concentrations of estradiol might be an additional pathogenetic factor for the development of CHD in menstrually active premenopausal women.

Adult↗