Effects of 17beta-estradiol on preadipocyte proliferation in human adipose tissue: Involvement of IGF1-R signaling.

Estrogens are known to stimulate the proliferation of human preadipocytes. However, the molecular mechanisms underlying the increased cell growth by these steroids are poorly understood. In the present study, we have demonstrated that the proliferative effect of 17beta-estradiol involves the induction of both cell cycle gene expressions, c-myc and cyclin D1.

Characterization and expression of netrin-1 and its receptors UNC5B and DCC in human placenta.

Netrins are a family of proteins that mediate axonal guidance in the central nervous system (CNS). In addition to the CNS, netrins are involved in cell adhesion, motility, proliferation, differentiation, and survival. Because these processes occur in the placenta, we raised the question of whether netrin-1 is expressed by placental cells during development.

Adiponectin mediates an antiproliferative response in human MDA-MB 231 breast cancer cells.

Numerous epidemiological studies have documented that obesity is a risk factor for breast cancer especially in post-menopausal women. However, the molecular basis of this association is not well known. In contrast to leptin, plasma levels of adiponectin, another major adipokine, are decreased in obese subjects.

Antiadipogenic properties of retinol in primary cultured differentiating human adipocyte precursor cells.

The aim of this study was to investigate the effect of retinol on the human adipose conversion process using primary cultured human adipocyte precursor cells. When these cells were seeded in a medium containing retinol (concentrations ranging from 3.5 nM to 3.

Expression studies of key adipogenic transcriptional factors reveal that the anti-adipogenic properties of retinol in primary cultured human preadipocytes are due to retinol per se.

The aim of this study was to investigate the mechanism(s) underlying the antiadipogenic effect of retinol that we recently reported in primary cultured human preadipocytes. Exposure of human preadipocytes to the potent alcohol dehydrogenase inhibitor, 4-methyl-pyrazole, failed to alter the antiadipogenic effect of retinol (3.5 microm), suggesting that the latter effect is due to retinol per se rather than to its oxidation product, retinoic acid (RA).

Increased achondroplasia mutation frequency with advanced age and evidence for G1138A mosaicism in human testis biopsies.

Objective: To evaluate the influence of aging on the achondroplasia mutation rate in the male germline.

Design: Studies in sperm and testis biopsy DNA according to donor's age.

Setting: University teaching hospital.

In vitro effects of chorionic gonadotropin hormone on human adipose development.

It is well known that pregnancy is associated with fat weight gain. However, the mechanisms whereby fat mass accumulation is controlled during this period are poorly understood. Therefore, we attempted to determine whether human chorionic gonadotropin (HCG), in vitro, influences human adipose tissue development and/or metabolism.

[Screening for Down syndrome using first-trimester combined screening followed by second trimester ultrasound examination in an unselected population].

Background: Recent studies have reported the efficacy of first trimester combined screening for Down Syndrome based on maternal age, serum markers (human chorionic gonadotropin, pregnancy-associated plasma protein A), and ultrasound measurement of fetal nuchal translucency. However, those do not incorporate the value of the widely accepted routine 20-22 week anomaly scan.

Study Design: We carried out a multi-centre, interventional study in the unselected population of a single health authority in order to assess the performance of first trimester combined screening, followed by routine second trimester ultrasound examination and/or screening by maternal serum markers (free beta-hCG and alpha-fetoprotein measurement or total hCG, alpha-fetoprotein and unconjugated estriol measurement) when incidentally performed.

Nongenomic estrogen effects on nitric oxide synthase activity in rat adipocytes.

Estrogens exert multiple genomic effects on adipose tissue through binding to nuclear estrogen receptors. However, there is evidence for additional nongenomic mechanisms whereby estrogens may exert their control on adipose tissue metabolism through rapid activation of various membrane-initiated kinase cascades. Here, we tested rapid effects of estrogens on nitric oxide production in white adipose tissue using 17-beta estradiol (E2) and its membrane impermeant albumin conjugated form (17-beta estradiol hemisuccinate BSA, E2-BSA).

Association between androgen receptor gene CAG trinucleotide repeat length and testicular histology in older men.

Objective: To determine whether the size of CAG repeat in exon 1 of the androgen receptor (AR) gene is related to impaired spermatogenesis in older men.

Design: Study of two groups of older men: one with preserved spermatogenesis and the other with arrested spermatogenesis.

Setting: University teaching hospital.

[Late paternity: spermatogenetic aspects].

The effect of maternal age on the risk of meiotic abnormality is well documented. In contrast little is known about the effect of the paternal age. The question of the risk related to paternal age is raised because of the increased demand of Assisted Reproduction Techniques for older men.

Screening for Down syndrome using first-trimester combined screening followed by second-trimester ultrasound examination in an unselected population.

Objective: Recent studies have reported the efficacy of first-trimester combined screening for Down syndrome based on maternal age, serum markers (human chorionic gonadotropin, pregnancy-associated plasma protein A), and ultrasound measurement of fetal nuchal translucency. However, those do not incorporate the value of the widely accepted routine 20-22 weeks' anomaly scan.

Study Design: We carried out a multicenter, interventional study in the unselected population of a single health authority in order to assess the performance of first-trimester combined screening, followed by routine second trimester ultrasound examination and/or screening by maternal serum markers (free beta-hCG and alpha-fetoprotein measurement or total hCG, alpha-fetoprotein, and unconjugated estriol measurement) when incidentally performed.

Adiponectin mediates antiproliferative and apoptotic responses in human MCF7 breast cancer cells.

It is well established that obesity is a risk factor for breast cancer and that blood levels of adiponectin, a hormone mainly secreted by white adipocytes, are inversely correlated with the body fat mass. As adiponectin elicits anti-proliferative effects in some cell types, we tested the hypothesis that adiponectin could influence human breast cancer MCF-7 cell growth. Here we show that MCF-7 cells express adiponectin receptors and respond to human recombinant adiponectin by reducing their growth, AMPkinase activation, and p42/p44 MAPkinase inactivation.

Sex steroids and leptin regulate 11beta-hydroxysteroid dehydrogenase I and P450 aromatase expressions in human preadipocytes: Sex specificities.

Adipose tissue is an important site of steroid hormone biosynthesis, as type I 11beta-hydroxysteroid dehydrogenase (HSD1), the enzyme responsible for the conversion of cortisone into cortisol and the P450 aromatase, the enzyme catalysing androgens aromatization into estrogens, are both expressed in human adipose tissue. In the present report, we have investigated the possibility that sex steroids and leptin could regulate these two enzymes in cultured preadipocytes from men and women intra-abdominal fat depots. In women preadipocytes, human recombinant leptin down-regulates HSD1 mRNA expression (-58%) and P450 aromatase activity (-26%).

Changes in progesterone-induced-blocking-factor expression rates following mifepristone administration in termination of pregnancy at 5 to 8 weeks.

Objective: To study changes in the expression rate of PIBF by peripheral lymphocytes in healthy pregnant women after administration of mifepristone for non-surgical termination of pregnancy at 5-8 wks of gestation.

Methods: Patients requesting early social termination of pregnancy, in a 3-month period, were included. A first venous blood sample was taken before oral administration of 600 mg of mifepristone (day 0).

Leptin-induced nitric oxide production in white adipocytes is mediated through PKA and MAP kinase activation.

Leptin injection increases plasma levels of nitrites and/or nitrates, an index of nitric oxide (NO) production. Because plasma levels of NO are correlated with fat mass and because adipose tissue is the main source of leptin, it seems that adipose tissue plays a major role in NO release induced by leptin. Adipocytes express both leptin receptors and nitric oxide synthase (NOS; including the endothelial isoform, NOS III, and the inducible isoform, NOS II).

Human adipose angiotensinogen gene expression and secretion are stimulated by cyclic AMP via increased DNA cyclic AMP responsive element binding activity.

Components of the adipose renin-angiotensin system (RAS) have been suggested as providing a potential path-way linking obesity to hypertension. In adipose cells, the biological responses to beta-adrenergic stimulation are mediated by an increase in intracellular cAMP. Because an association exists among body fat mass, hypertension, and increased sympathetic stimulation, we examined the influence of cAMP on angiotensinogen (ATG) expression and secretion in human adipose tissue and in parallel we studied the DNA binding activity of CRE transcriptional factors.

Evidence for functional estrogen receptors alpha and beta in human adipose cells: regional specificities and regulation by estrogens.

Adipocytes are estrogen-responsive cells, but the quantitative expression and transcriptional regulation of the estrogen receptors (ER-alpha and ER-beta) in human adipocytes and their precursor cells are unclear. Using real-time quantitative PCR, we have demonstrated that both ER-alpha and ER-beta mRNA are expressed in human mature adipocytes with a large predominance of ER-alpha mRNA. Moreover, ER-alpha mRNA is identically expressed whatever the anatomic origin (intraabdominal and subcutaneous) of the adipocytes and the gender.

cAMP-positive regulation of angiotensinogen gene expression and protein secretion in rat adipose tissue.

The adipose renin-angiotensin system (RAS) has been assigned to participate in the control of adipose tissue development and in the pathogenesis of obesity-related hypertension. In adipose cells, the biological responses to beta-adrenergic stimulation are mediated by an increase in intracellular cAMP. Because cAMP is known to promote adipogenesis and because an association exists between body fat mass, hypertension, and increased sympathetic stimulation, we examined the influence of cAMP on angiotensinogen (ATG) expression and secretion in rat adipose tissue.

In vitro suppression of the lipogenic pathway by the nonnucleoside reverse transcriptase inhibitor efavirenz in 3T3 and human preadipocytes or adipocytes.

A serious metabolic syndrome combining insulin-resistance, dyslipidemia, central adiposity, and peripheral lipoatrophy has arisen in HIV-infected patients receiving highly active antiretroviral therapy. The aim of this work was to examine the effects of the nonnucleoside reverse transcriptase inhibitor (NNRTI) efavirenz on adipocyte differentiation and metabolism. When induced to differentiate in the presence of efavirenz (5-50 microm), 3T3-F442A preadipocytes failed to accumulate cytoplasmic triacylglycerol droplets.

Hypothalamic leptin receptor and signaling molecule expressions in cafeteria diet-fed rats.

Although obesity is associated with a state of leptin resistance, it has been suggested that leptin may contribute to the pathogenesis of obesity-related hypertension. In previous studies, we reported that cafeteria diet feeding induces hyperleptinaemia and hyperinsulinemia in both male and female rats, with hypertension occurring only in male rats. However, when female rats were neonatally treated with testosterone (T), these animals develop hypertension when fed the cafeteria diet.

Fibrinogen Poissy II (gammaN361K): a novel dysfibrinogenemia associated with defective polymerization and peptide B release.

A fibrinogen variant was identified in a pregnant patient with disseminated intravascular coagulation and abruptio placentae. This dysfibrinogen was also found in four asymptomatic members of the patient's family. Coagulation studies showed prolongation of both the thrombin and reptilase times, and discrepancy was noted between the levels of plasma fibrinogen as determined by a kinetic versus an immunological determination or light-scattering assay.

Sexual dimorphism in cafeteria diet-induced hypertension is associated with gender-related difference in renal leptin receptor down-regulation.

Plasma leptin levels are elevated in obesity suggesting a pathophysiologic role of this hormone in obesity and related disorders, such as hypertension. Furthermore, despite excess leptin levels, leptin satiety action is blunted in obesity suggesting the occurrence of central leptin resistance. As leptin acts on the kidney to induce natriuresis, renal leptin receptor alterations could lead to a defect in sodium excretion and hence to hypertension.