Search Results

You are looking at 91 - 100 of 2,825 items for :

  • "enhancers" x
Clear All
Free access

Sayaka Aizawa, Takafumi Sakai and Ichiro Sakata

00000008465 2944.3 1508.1 2061.1 MEA1 Male-enhanced antigen ENSRNOG00000017144 2929.1 6413.2 2378.1 RT1-KE4 RT1 class I, locus Ke4 ENSRNOG00000000465 2853.1 1557.8 1889.8 MXRA8 Matrix-remodeling-associated protein 8 precursor (limitrin) ENSRNOG00000019244 2820

Free access

Yan Zhou, Jacob Bendor, Lauren Hofmann, Matthew Randesi, Ann Ho and Mary Jeanne Kreek

levels. We extended our studies to investigate the effects of 12 h spontaneous morphine withdrawal, and found an increase in MOP-r mRNA levels in the lat.hyp. This increase in MOP-r mRNA levels after morphine withdrawal suggests an enhanced MOP

Free access

M Takamoto, K Tsuji, T Yamashita, H Sasaki, T Yano, Y Taketani, T Komori, A Nifuji and M Noda

Hedgehog signaling is considered to play a crucial role in chondrogenesis by regulation through a network of cytokine actions, which is not fully understood. We examined the effect of hedgehog signaling on the expression of core-binding factor a1 (Cbfa1), a critical transcription factor for the development of bone and cartilage. Primary chondrocytes prepared from the costal cartilage of newborn mice were treated with N-terminal fragment of recombinant murine sonic hedgehog (rmShh-N). Northern blot analysis indicated that Cbfa1 mRNA expression levels in the chondrocyte cultures were elevated by the treatment with rmShh-N. rmShh-N treatment enhanced 1.8 kb Cbfa1 promoter activity in chondrocytes, suggesting the presence of transcriptional control. As Cbfa1-binding site(s) have been located in the promoter of the receptor activator of nuclear factor-kappaB (RANK) ligand (RANKL) gene, we also examined RANKL expression. rmShh-N treatment upregulated RANKL and RANK mRNA expression levels in chondrocytes. Interestingly, RANKL suppressed the hedgehog enhancement of alkaline phosphatase activity in chondrocytes, suggesting the presence of a link between these signaling molecules. We conclude that hedgehog signaling activates Cbfa1 gene expression through its promoter in chondrocytes, and also activates and interacts with RANKL to maintain cartilage development.

Free access

GF Gonzales, A Cordova, K Vega, A Chung, A Villena and C Gonez

Lepidium meyenii (Maca) is a Peruvian hypocotyl that grows exclusively between 4000 and 4500 m in the central Andes. Maca is traditionally employed in the Andean region for its supposed aphrodisiac and/or fertility-enhancing properties. This study was a 12-week double-blind, placebo-controlled, randomized, parallel trial in which active treatment with different doses of Maca Gelatinizada was compared with a placebo. The study aimed to test the hypothesis that Maca has no effect on serum reproductive hormone levels in apparently healthy men when administered in doses used for aphrodisiac and/or fertility-enhancing properties. Men aged between 21 and 56 Years received 1500 mg or 3000 mg Maca. Serum levels of luteinizing hormone, follicle-stimulating hormone, prolactin, 17-alpha hydroxyprogesterone, testosterone and 17-beta estradiol were measured before and at 2, 4, 8 and 12 weeks of treatment with placebo or Maca (1.5 g or 3.0 g per day). Data showed that compared with placebo Maca had no effect on any of the hormones studied nor did the hormones show any changes over time. Multiple regression analysis showed that serum testosterone levels were not affected by treatment with Maca at any of the times studied (P, not significant). In conclusion, treatment with Maca does not affect serum reproductive hormone levels.

Free access

RC Fowkes and JM Burrin

Steroidogenic factor-1 (SF-1) is a key regulator of endocrine development, and mediates expression of gonadotrophin-specific genes in the pituitary. Basal and hormone stimulated transcription of the human glycoprotein hormone alpha-subunit gene (alphaGSU) in gonadotrophs involves SF-1 and its cognate binding site, the gonadotroph-specific element (GSE). In this study, we demonstrate that SF-1 significantly enhances basal and forskolin-stimulated transcription of the human alphaGSU promoter in GH(3) cells. Mutation of the GSE abolished the SF-1-mediated transactivation of basal alphaGSU promoter activity, and significantly attenuated the forskolin effect by 50%. Mutation of the Ser203 residue in SF-1 to Ala blocked basal transactivation of alphaGSU promoter activity, and halved the forskolin effect. These data collectively reveal a direct role for SF-1 and the GSE in mediating basal and forskolin-stimulated transcription of the human alphaGSU promoter in GH(3) cells. The phosphorylation site at Ser203 appears to be required for these effects.

Restricted access

S Hundertmark, H Buhler, M Rudolf, HK Weitzel and V Ragosch

This in vitro study on MCF-7 and ZR-75-1 breast cancer cells showed that the antiproliferative action of glucocorticosteroids (GCS) on breast cancer cells is weakened by a high oxidative activity of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD; EC 1.1.1.146): both endogenic as well as synthetic GCS (dexamethasone, prednisolone) were metabolised to hormonally inactive 11-dehydro metabolites. This enzymatic shield protected the breast cancer cells from the antiproliferative action of GCS. Continuous exposure of breast cancer cells to GCS resulted in enhanced 11 beta-HSD activity. The intracellular GCS concentration was further reduced by this feedback and thus the antiproliferative effect was additionally weakened. These mechanisms of GCS deactivation could be influenced by inhibiting 11 beta-HSD with the liquorice compound glycyrrhetinic acid (GLY). In MCF-7 and ZR-75-1 cultures the antiproliferative effect of GCS was significantly increased by GLY.

Free access

C Anneren

Transgenic CBA mice expressing either the tyrosine kinase GTK (gut tyrosine kinase) or the adaptor protein SHB (Src homology 2 protein of beta-cells) under the control of the rat insulin promoter exhibited an increased beta-cell mass, but also elevated cytokine-induced islet cell death compared with control mice. To further investigate the importance of GTK and SHB for beta-cell death and proliferation, these mice were subjected to a 60% partial pancreatectomy (Px) or a sham-operation and beta-cell replication was determined by autoradiographic detection of [(3)H]thymidine incorporation into islet cells positively stained for insulin. The Px-operated control mice exhibited a moderate and insignificant increase in beta-cell replication 4 days after Px compared with the sham-operated mice (0.27+/-0.08% vs 0.08+/-0.02%). In contrast, the Px-induced beta-cell proliferation was significantly increased in both the GTK- and SHB-transgenic mice compared with the corresponding sham-treated animals (0.64+/-0.12% vs 0.11+/-0.04% and 0.44+/-0.11% vs 0.09+/-0.04% respectively). This effect was dependent on intracellular signal transduction pathways activated or enhanced by GTK and SHB overexpression, since the proliferation of acinar cells, located in the vicinity of the islets, was equal in the transgenic and control mice. GTK- and SHB-transgenic mice, treated with a sub-diabetogenic dose of the beta-cell toxin streptozotocin (STZ) on day 0 and subjected to a glucose tolerance test on day 3, exhibited an impaired glucose tolerance in comparison with the STZ-treated control mice. Pretreatment with STZ blunted the regenerative response to Px in the transgenic mice. Furthermore, the SHB-transgenic islets were significantly more damaged with respect to beta-cell loss, compared with the islets of the control mice. Previous and present data suggest a dual role of GTK and SHB for beta-cell growth: whereas these proteins increase the beta-cell mass and induce beta-cell proliferation after 60% Px, SHB and GTK also enhance beta-cell death under certain stressful conditions.

Restricted access

NO Vidal, S Ekberg, S Enerback, A Lindahl and C Ohlsson

The transcription factor C/EBP alpha, a member of the CCAAT/enhancer-binding protein family, is highly expressed in the liver and in adipose tissue. The aim of this study was to determine if C/EBP alpha is expressed in rat growth cartilage. The expression pattern of C/EBP alpha in monolayer-cultured growth plate chondrocytes was similar to that of C/EBP alpha during hepatocyte and preadipocyte differentiation. Immunohistochemistry with a polyclonal antibody for C/EBP alpha revealed that the C/EBP alpha protein is present in the perichondrial ring, in the germinal layer of the growth plate and on the surface of the articular cartilage. The growth hormone (GH) receptor has a similar distribution in the rat tibial growth plate, and hypophysectomised rats were used to investigate a possible connection between C/EBP alpha and GH. C/EBP alpha mRNA levels were decreased in rib cartilage after hypophysectomy. However, GH treatment did not counteract this effect, indicating that other pituitary hormones regulate the C/EBP alpha mRNA levels in growth plate cartilage. We thus demonstrate, for the first time, that C/EBP alpha is expressed in cartilage. The finding that C/EBP alpha, like the GH receptor, is predominantly expressed in stem cell areas of the rat growth plate indicates a possible functional role for C/EBP alpha during early chondrogenic differentiation.

Restricted access

J. R. Bassett

ABSTRACT

Exposure of rats to either footshock or handling stress produced a significant increase in both plasma corticosterone concentration and specific binding capacity. Non-specific binding was eliminated using the synthetic glucocorticoid, dexamethasone. The increase in both plasma corticosterone and specific binding capacity was biphasic following exposure to footshock. Adrenalectomy and pretreatment with betamethasone abolished both phases of the enhanced binding capacity and plasma steroid concentration. Intraperitoneal injection of ACTH (1–24) in animals pretreated with betamethasone resulted in a biphasic rise in plasma concentrations of corticosterone but only the initial increase in binding capacity. Dissociation constant (K d) values, determined by Scatchard analysis, for adrenalectomized and betamethasone-pretreated animals were 546 and 556 pmol/l respectively. These values were significantly different from the K d in animals with functional adrenals (631 pmol/l). The results are discussed in the light of a possible specific corticosteroid-binding globulin (CBG)-like binding protein of adrenal origin released in conjunction with corticosterone. This binding protein has a lower affinity for corticosterone and a shorter half-life than CBG.

J. Endocr. (1987) 112, 33–41

Free access

ES Vizi, J Szelenyi, ZS Selmeczy, Z Papp, ZH Nemeth and G Hasko

It is increasingly apparent that there is a bidirectional interaction between the maternal immune system and the reproductive system during pregnancy. Pregnancy is associated with a suppression of maternal specific immune responses, which process underlies the protection of fetal tissues expressing paternally inherited alloantigens. However, recent evidence indicates that the suppression of specific, lymphocyte-mediated immune responses during pregnancy is accompanied by activation of the non-specific arm of the maternal immune response. In the present study, we have investigated the effect of pregnancy on the non-specific immune response induced by bacterial lipopolysaccharide (LPS, endotoxin) in mice. Pregnancy enhanced the LPS-induced production of proinflammatory cytokines, including tumor necrosis factor-alpha, interleukin (IL)-6, and interferon-gamma. On the other hand, LPS-induced levels of the anti-inflammatory cytokine IL-10 were suppressed in pregnant mice. These alterations in cytokine production correlated with an increased susceptibility for endotoxemic mortality in the pregnant mice. Although adrenergic receptors are important regulators of cytokine production in non-pregnant mice, the alpha(2)- and the beta-adrenoceptor-mediated modulation of cytokine production ceases to operate during pregnancy associated with severe endotoxemia. These data may explain how excessive activation of the non-specific immune responses during pregnancy can contribute to the increased severity of some maternal diseases, including septic shock, and can be an important pathophysiological factor in disseminated intravascular coagulation or preeclampsia.