Construction of Egr1-mediated human truncated apoptosis inducing factor expression vector and its expression regularity induced by radiation in breast cancer MCF-7 cells

International Nuclear Information System (INIS)

Wang Jianfeng; Gong Shouliang; Wang Zhicheng; Fang Fang; Liu Yang; Wu Jiahui

2012-01-01

Objective: To clone human truncated apoptosis inducing factor (AIF) cDNA sequence, and to construct early growth response 1 (Egr1)-mediated recombinant expression vector pcDNA 3.1-Egr1-AIF Δ1-480 (pEgr1-AIFΔ 1-480 ), and to observe its regularity induced by radiation in human breast cancer MCF-7 cells. Methods: The total mRNA extracted from human leukemia Jurkat cells used as template, and the human AIFΔ 1-480 was acquired by RT-PCR, and it was linked to pMD18T vector for sequencing. Egr1 fragment was digested from pMD19T-Egr1 by restrictive enzyme, and the Egr1-mediated expression plasmid pEgr1-AIFΔ 1-480 was constructed by gene recombination. There were control group, pcDNA3.1 group, pAIFΔ 1-480 group and pEgr1-AIFΔ 1-480 group in the experiment. After the plasmids in various groups were transfected into human breast cancer MCF-7 cells, the AIF and AIFΔ 1-480 protein expression time-effect (0, 2, 4, 12, 24 and 48 h after 2.0 Gy irradiation) and dose-effect (24 h after 0, 0.2, 0.5, 1.0, 2.0 and 5.0 Gy irradiation) regularity were measured by Western blotting method. Results: The sequencing results showed that the AIFΔ 1-480 acquired by RT-PCR was consistent with the sequence expected, the pEgr-AIFΔ 1-480 was confirmed by PCR and restrictive enzyme digestion. After 0-48 h the MCF-7 cells were irradiated by 2.0 Gy, and the AIF protein expressed in the cells in each group, and it increased significantly from 4 h and the AIF expressions in 4, 12, 24 and 48 h groups were higher than that in 0 h group (P<0.05), and it reached to maximum value at 48 h. But the AIFΔ 1-480 protein expressed in the cells in pAIFΔ 1-480 and pEgr1-AIFΔ 1-480 groups from 2 h (P<0.05), and it reached to peak value at 24 h. The AIFΔ 1-480 expressions in pEgr1-AIFΔ 1-480 group were higher than those in pAIFΔ 1-480 group at and 48 h (P<0.05). After the MCF-7 cells were irradiated by 0-5 Gy for 24 h, the AIF protein expressed in the cells in each group, but the AIFΔ 1-480 protein

Egr-1 induction provides a genetic response to food aversion in zebrafish

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Brigitte eBoyer

2013-05-01

Full Text Available As soon as zebrafish larvae start eating, they exhibit a marked aversion for bitter and acidic substances, as revealed by a consumption assay, in which fluorescent Tetrahymena serve as a feeding basis, to which various stimuli can be added. Bitter and acidic substances elicited an increase in mRNA accumulation of the immediate-early response gene egr-1, as revealed by in situ hybridization. Conversely, chemostimulants that did not induce aversion did not induce egr-1 response. Maximum labelling was observed in cells located in the oropharyngeal cavity and on the gill rakers. Gustatory areas of the brain were also labelled. Interestingly, when bitter tastants were repeatedly associated with food reward, zebrafish juveniles learned to ingest food in the presence of the bitter compound. After habituation, the acquisition of acceptance for bitterness was accompanied by a loss of egr-1 labelling. Altogether, our data indicate that egr-1 participates specifically in food aversion. The existence of reward-coupled changes in taste sensitivity in humans suggests that our results are relevant to situations in humans.

Egr-1 induction provides a genetic response to food aversion in zebrafish.

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Boyer, Brigitte; Ernest, Sylvain; Rosa, Frédéric

2013-01-01

As soon as zebrafish larvae start eating, they exhibit a marked aversion for bitter and acidic substances, as revealed by a consumption assay, in which fluorescent Tetrahymena serve as a feeding basis, to which various stimuli can be added. Bitter and acidic substances elicited an increase in mRNA accumulation of the immediate-early response gene egr-1, as revealed by in situ hybridization. Conversely, chemostimulants that did not induce aversion did not induce egr-1 response. Maximum labeling was observed in cells located in the oropharyngeal cavity and on the gill rakers. Gustatory areas of the brain were also labeled. Interestingly, when bitter tastants were repeatedly associated with food reward, zebrafish juveniles learned to ingest food in the presence of the bitter compound. After habituation, the acquisition of acceptance for bitterness was accompanied by a loss of egr-1 labeling. Altogether, our data indicate that egr-1 participates specifically in food aversion. The existence of reward-coupled changes in taste sensitivity in humans suggests that our results are relevant to situations in humans.

TRAIL overexpression co-regulated by Egr1 and HRE enhances radiosensitivity of hypoxic A549 cells depending on its apoptosis inducing role.

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Yang, Yan-Ming; Fang, Fang; Li, Xin; Yu, Lei; Wang, Zhi-Cheng

2017-01-01

Ionizing radiation can upregulate the expression levels of TRAIL and enhance tumor cell apoptosis. While Early growth response 1 (Egr1) gene promoter has radiation inducible characteristics, the expression for exogenous gene controlled by Egr1 promoter could be enhanced by ionizing radiation, but its efficiency is limited by tissue hypoxia. Hypoxia response elements (HREs) are important hypoxic response regulatory sequences and sensitivity enhancers. Therefore, we chose TRAIL as the gene radiotherapy to observe whether it is regulated by Egr1 and HER and its effects on A549 cells and its mechanism. The pcDNA3.1-Egr1-TRAIL (pc-E-hsT) and pcDNA3.1-HRE/Egr1-TRAIL (pc-H/E-hsT) plasmids containing Egr1-hsTRAIL and HRE/Egr1-hsTRAIL were transfected into A549 cells, the cells were treated by hypoxia and radiation. The TRAIL mRNA in the cells and protein concentration in the culture supernatants were measured by RT-PCR and ELISA, respectively. Mean lethal dose D0 value was evaluated with colony forming assay. The cell apoptotic rates were analyzed by FCM and TUNEL assay. Expression of DR4, DR5 and cleaved caspase-3 proteins were analyzed by western blotting. It showed that TRAIL mRNA expression and TRAIL concentration all significantly increased under hypoxia and/or radiation. D0 value of pc-H/E‑hsT transfected cells under hypoxia was lowest, indicating more high radiosensitivity. Hypoxia could not cause the pc-E-hsT transfected cell apoptotic rate increase, but there were promoting effects in pc-H/E-hsT transfected cells. DR4 had not obvious change in pc-E-hsT and pc-H/E-hsT transfected cells under normoxic and hypoxic condition, otherwise, DR5 and cleaved caspase-3 increased mostly in pc-H/E-hsT transfected cells under hypoxic condition. TRAIL overexpression was co-regulated by Egr1 and HRE. TRAIL might promote hypoxic A549 cell radiosensitivity and induce apoptosis depending on DR5 to caspase-3 pathways.

Construction of recombinant adenovirus with Egr-1 promoter and Smad7 cDNA and study of the Egr-1 promoter's biological activity

International Nuclear Information System (INIS)

Cai Xuwei; Fu Xiaolong; Yang Jian; Song Houyan

2005-01-01

Objective: To construct a recombinant replication-defective adenovirus containing Egr-1 promoter and Smad7 cDNA, then to evaluate the biological activity of Egr-1 promoter. Methods: Based on Adeno- X TM expression system, CMV promoter of the pShuttle vector was replaced by Egr-1 promoter, and the Smad7 cDNA was subcloned into the MCS(multiple cloning site) of pShuttle. The recombinant pShuttle was then sub-cloned into the Adeno-X TM genome, which was transformed into E. coli to get recombinant Adeno-X TM plasmid DNA. The recombinant adenovirus was packaged and amplified in the transfected HEK293 cells before it was purified and tested for viral titer. The fibroblasts (3T6 cells) infected by the recombinant adenovirus were irradiated , and the activity of Egr-1 promoter was quantitively determined by the amount of Smad7 protein expressed in the 3T6 cells using Western blot. Results: Identified by restriction endonuclease analysis and PCR, the recombinant adenovirus containing Egr-1 promoter and Smad7 cDNA was constructed successfully, with a viral titer of 1.0 x 10 11 TCID 50 /ml. The expressed amount of Smad7 protein varied at different dose levels and different time points post-irradiation in the 3T6 cells infected with the recombinant adenovirus. The amount of Smad7 protein increased along with the rising of the irradiation dose, and remained at a high expression level from 8 Gy to 15 Gy. The amount of Smad7 protein started to increase at 2 hours post-irradiation, and maintained a relatively high level for the next 5 hours before it descended, which was not observed in the control 3T6 cells. Conclusions: With the aid of Adeno-X TM expression system and molecular cloning techniques, construction of recombinant adenovirus could be quick and efficient. The recombined Egr-1 promoter has the activity of regulating the expression of downstream Smad7 cDNA. The increase in Smad7 expression under control of Egr-1 promoter induced by ionizing radiation is time- and dose

Egr2 induced during DC development acts as an intrinsic negative regulator of DC immunogenicity.

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Miah, Mohammad Alam; Byeon, Se Eun; Ahmed, Md Selim; Yoon, Cheol-Hee; Ha, Sang-Jun; Bae, Yong-Soo

2013-09-01

Early growth response gene 2 (Egr2), which encodes a zinc finger transcription factor, is rapidly and transiently induced in various cell types independently of de novo protein synthesis. Although a role for Egr2 is well established in T-cell development, Egr2 expression and its biological function in dendritic cells (DCs) have not yet been described. Here, we demonstrate Egr2 expression during DC development, and its role in DC-mediated immune responses. Egr2 is expressed in the later stage of DC development from BM precursor cells. Even at steady state, Egr2 is highly expressed in mouse splenic DCs. Egr2-knockdown (Egr2-KD) DCs showed increased levels of major histocompatability complex (MHC) class I and II and co-stimulatory molecules, and enhanced antigen uptake and migratory capacities. Furthermore, Egr2-KD abolished SOCS1 expression and signal transducer and activator of transcription 5 (STAT5) activation during DC development, probably resulting in the enhancement of IL-12 expression and Th1 immunogenicity of a DC vaccine. DC-mediated cytotoxic T lymphocyte (CTL) activation and antitumor immunity were significantly enhanced by Egr2-KD, and impaired by Egr2 overexpression in antigen-pulsed DC vaccines. These data suggest that Egr2 acts as an intrinsic negative regulator of DC immunogenicity and can be an attractive molecular target for DC vaccine development. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PPARa and PPAR¿ coactivation rapidly induces Egr-1 in the nuclei of the dorsal and ventral urinary bladder and kidney pelvis urothelium of rats

DEFF Research Database (Denmark)

Egerod, Frederikke Lihme; Svendsen, Jette Eldrup; Hinley, Jennifer

2009-01-01

in the dorsal and ventral bladder urothelium, arguing against involvement of urinary solids. Egr-1 induction sometimes occurred in a localized fashion, indicating physiological microheterogeneity in the urothelium. The rapid kinetics supported that Egr-1 induction occurred as a result of pharmacological...... activation of PPAR alpha and PPAR gamma, which are coexpressed at high levels in the rat urothelium. Finally, our demonstration of a nuclear localization supports that the Egr-1 induced by PPAR alpha and PPAR gamma coactivation in the rat urothelium may be biologically active....

EGR-1 and DUSP-1 are important negative regulators of pro-allergic responses in airway epithelium.

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Golebski, Korneliusz; van Egmond, Danielle; de Groot, Esther J; Roschmann, Kristina I L; Fokkens, Wytske J; van Drunen, Cornelis M

2015-05-01

Primary nasal epithelium of house dust mite allergic individuals is in a permanently activated inflammatory transcriptional state. To investigate whether a deregulated expression of EGR-1 and/or DUSP-1, two potential negative regulators of pro-inflammatory responses, could contribute to the activation of the inflammatory state. We silenced the expression of EGR-1 or DUSP-1 in the airway epithelial cell line NCI-H292. The cell lines were stimulated in a 24-h time course with the house dust mite allergen or poly(I:C). RNA expression profiles of cytokines were established using q-PCR and protein levels were determined in supernatants with ELISA. The shRNA-mediated gene silencing reduced expression levels of EGR-1 by 92% (p<0.0001) and of DUSP-1 by 76% (p<0.0001). Both mutant cells lines showed an increased and prolonged response to the HDM allergen. The mRNA induction of IL-6 was 4.6 fold (p=0.02) and 2.4 fold higher (p=0.01) in the EGR-1 and DUSP-1 knock-down, respectively when compared to the induced levels in the control cell line. For IL-8, the induction levels were 4.6 fold (p=0.01) and 13.0 (p=0.001) fold higher. The outcome was largely similar, yet not identical at the secreted protein levels. Furthermore, steroids were able to suppress the poly(I:C) induced cytokine levels by 70-95%. Deregulation of EGR-1 and/or DUSP-1 in nasal epithelium could be responsible for the prolonged activated transcriptional state observed in vivo in allergic disease. This could have clinical consequences as cytokine levels after the steroid treatment in EGR-1 or DUSP-1 knock-down remained higher than in the control cell line. Copyright © 2015 Elsevier Ltd. All rights reserved.

转录因子Egr-1参与长期性恐惧记忆和焦虑%Transcription factor Egr-1 is required for long-term fear memory and anxiety

Institute of Scientific and Technical Information of China (English)

Shanelle; W．Ko; 敖虎山; Amelia; Gallitano-Mendel; 邱长申; 魏峰; Jeffrey; Milbrandt; 卓敏

2005-01-01

The zinc finger transcription factor Egr-1 is critical for coupling extracellular signals to changes in cellular gene expression.In the hippocampus and amygdala, two major central regions for memory formation and storage, Egr-1 is up-regulated by long-term potentiation (LTP) and learning paradigms. Using Egr-1 knockout mice, we showed that Egr-1 was selectively required for late auditory fear memory while short term, trace and contextual memory were not affected. Additionally, synaptic potentiation induced by theta burst stimulation in the amygdala and auditory cortex was significantly reduced or blocked in Egr-1 knockout mice. Our study suggests that the transcription factor Egr-1 plays a selective role in late auditory fear memory.%锌指转录因子Egr-1在将细胞外信号和胞内基因表达的变化相耦联过程中发挥重要的作用.海马和杏仁体是记忆形成和储存的两个主要的脑区.在海马和杏仁体中,Egr-1可被长时程增强(long-term potentiation,LTP)和学习过程上调.在Egr-1敲除小鼠上观察到晚时相声音恐惧记忆受损,而短时的痕迹和场景记忆却不受影响;另外,在Egr-1敲除小鼠上,用thetaburst刺激杏仁体和听觉皮层所引起的突触增强被明显减弱或完全阻断.因此,我们的研究表明,转录因子Egr-1选择性地在晚时相听觉恐惧记忆中发挥作用.

Brain prolactin is involved in stress-induced REM sleep rebound.

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Machado, Ricardo Borges; Rocha, Murilo Ramos; Suchecki, Deborah

2017-03-01

REM sleep rebound is a common behavioural response to some stressors and represents an adaptive coping strategy. Animals submitted to multiple, intermittent, footshock stress (FS) sessions during 96h of REM sleep deprivation (REMSD) display increased REM sleep rebound (when compared to the only REMSD ones, without FS), which is correlated to high plasma prolactin levels. To investigate whether brain prolactin plays a role in stress-induced REM sleep rebound two experiments were carried out. In experiment 1, rats were either not sleep-deprived (NSD) or submitted to 96h of REMSD associated or not to FS and brains were evaluated for PRL immunoreactivity (PRL-ir) and determination of PRL concentrations in the lateral hypothalamus and dorsal raphe nucleus. In experiment 2, rats were implanted with cannulas in the dorsal raphe nucleus for prolactin infusion and were sleep-recorded. REMSD associated with FS increased PRL-ir and content in the lateral hypothalamus and all manipulations increased prolactin content in the dorsal raphe nucleus compared to the NSD group. Prolactin infusion in the dorsal raphe nucleus increased the time and length of REM sleep episodes 3h after the infusion until the end of the light phase of the day cycle. Based on these results we concluded that brain prolactin is a major mediator of stress-induced REMS. The effect of PRL infusion in the dorsal raphe nucleus is discussed in light of the existence of a bidirectional relationship between this hormone and serotonin as regulators of stress-induced REM sleep rebound. Copyright © 2016 Elsevier Inc. All rights reserved.

Construction of pEgr.p-TNFα and its expression in NIH3T3 cells induced by ionizing irradiation

International Nuclear Information System (INIS)

Wu Congmei; Li Xiuyi; Liu Shuzheng

2001-01-01

Objective: To isolate and amplify Egr-1 promoter, construct pEgr.p-TNFα and study its response to different doses of ionizing radiation. Methods: Egr-1 promote was isolated from genomic DNA by PCR to construct pEgr.p-TNFα expression plasmid. Plasmids were transfected into NIH3T3 cells with liposome and the expression level of TNFα was detected by ELISA after irradiation with different doses of X-ray. Results: The sequence of Egr-1 promoter obtained was essentially same as reported. Egr-1 promoter and TNF α cDNA were inserted into expression vector correctly. Eight hours after irradiation with different doses of X-rays, the expression level of TNFα was higher than that of nonirradiated group (P< 0.05-0.001). Conclusion: Egr-1 promoter obtained can be activated by ionizing irradiation and regulate the expression of downstream gene. Low dose irradiation is for the first time found to be able to induce the expression of the downstream gene. the observation may be of potential significance in tumor therapy

Function of the EGR-1/TIS8 radiation inducible promoter in a minimal HSV-1 amplicon system

International Nuclear Information System (INIS)

Spear, M.A.; Sakamoto, K.M.; Herrlinger, U.; Pechan, P.; Breakefield, X.O.

1997-01-01

Purpose: To evaluate function of the EGR-1/TIS8 promoter region in minimal HSV-1 amplicon system in order to determine the feasibility of using the system to regulate vector replication with radiation. Materials and Methods: A 600-base pair 5' upstream region of the EGR-1 promoter linked to chloramphenicol acetyltransferase (CAT) was recombined into a minimal HSV-1 amplicon vector system (pONEC). pONEC or a control plasmid was transfected into U87 glioma cells using the Lipofectamine method. Thirty-six hours later one aliquot of cells from each transfection was irradiated to a dose of 20 Gy and another identical aliquot served as a control. CAT activity was assayed 8 hours after irradiation. Results: pONEC transfected cells irradiated with 20 Gy demonstrated 2.0 fold increase in CAT activity compared to non-irradiated cells. Cells transfected with control plasmid showed no change in CAT activity. Unirradiated pONEC cells had CAT activity 1.3 times those transfected with control plasmid. Conclusion: We have previously created HSV-1 gene therapy amplicon vector systems which allow virus-amplicon interdependent replication, with the intent of regulating replication. The above data demonstrates that a minimal amplicon system will allow radiation dependent regulation by the EGR-1 promoter, thus indicating the possibility of using this system to regulate onsite, spatially and temporally regulated vector production. Baseline CAT activity was higher and relative induction lower than other reported expression constructs, which raises concern for the ability of the system to produce a differential in transcription levels sufficient for this purpose. This is possibly the result of residual promoter/enhancer elements remaining in the HSV-1 sequences. We are attempting to create constructs lacking these elements. Addition of secondary promoter sequences may also be of use. We are also currently evaluating the efficacy of the putative IEX-1 radiation inducible promoter region in

Transcriptional regulation of the p73 gene, a member of the p53 family, by early growth response-1 (Egr-1)

International Nuclear Information System (INIS)

Lee, Sang-Wang; Kim, Eun-Joo; Um, Soo-Jong

2007-01-01

To elucidate the regulatory mechanism of p73 gene expression, we analyzed the human p73 promoter and found three putative Egr-1-binding sites located upstream of exon 1 (-1728, -321, and -38). The Egr-1 responsiveness of these sites was analyzed by transient transfection assays using 5'- and 3'-serial truncations of the p73 promoter, subcloned in a CAT reporter vector. The functional significance of the region was further confirmed by an electrophoretic mobility shift assay using the Egr-1 protein synthesized in vitro and a [ 32 P]-labeled middle site sequence, followed by competition with unlabeled wild-type or mutant oligonucleotides and supershift assays using an anti-Egr-1 antibody. When induced by either the nitric oxide donor NOC-18 or the PPARγ agonist troglitazone, Egr-1 bound to the p73 promoter, as assessed by chromatin immunoprecipitation assays, accompanied by increased expression of p73. MTT assays revealed that cell growth was significantly inhibited on treating the cells with troglitazone. Overall, our results provide direct evidence that Egr-1 positively regulated p73 expression by binding to its promoter in vivo, consistent with Egr-1 and p73 being involved in p53-independent tumor suppression

Egr-1 activation by cancer-derived extracellular vesicles promotes endothelial cell migration via ERK1/2 and JNK signaling pathways.

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Yae Jin Yoon

Full Text Available Various mammalian cells, including cancer cells, shed extracellular vesicles (EVs, also known as exosomes and microvesicles, into surrounding tissues. These EVs play roles in tumor growth and metastasis by promoting angiogenesis. However, the detailed mechanism of how cancer-derived EVs elicit endothelial cell activation remains unknown. Here, we provide evidence that early growth response-1 (Egr-1 activation in endothelial cells is involved in the angiogenic activity of colorectal cancer cell-derived EVs. Both RNA interference-mediated downregulation of Egr-1 and ERK1/2 or JNK inhibitor significantly blocked EV-mediated Egr-1 activation and endothelial cell migration. Furthermore, lipid raft-mediated endocytosis inhibitor effectively blocked endothelial Egr-1 activation and migration induced by cancer-derived EVs. Our results suggest that Egr-1 activation in endothelial cells may be a key mechanism involved in the angiogenic activity of cancer-derived EVs. These findings will improve our understanding regarding the proangiogenic activities of EVs in diverse pathological conditions including cancer, cardiovascular diseases, and neurodegenerative diseases.

Effects of LHRH and ANG II on prolactin stimulation are mediated by hypophysial AT1 receptor subtype.

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Becú-Villalobos, D; Lacau-Mengido, I M; Thyssen, S M; Díaz-Torga, G S; Libertun, C

1994-02-01

We have used the nonpeptide angiotensin II (ANG II) receptor antagonists losartan (receptor subtype AT1) and PD-123319 (AT2) to determine the participation of ANG II receptor subtypes in luteinizing hormone-releasing hormone (LHRH)-induced prolactin release in a perifusion study using intact pituitaries in vitro. LHRH (1.85 x 10(-7) M) released prolactin consistently, whereas losartan (10(-5) M) abolished prolactin response without modifying basal prolactin or luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release. PD-123319 (10(-5) M) had no effect on basal or LHRH-induced prolactin, LH, or FSH release. We also determined that the effect of ANG II on prolactin release was mediated by the same receptor subtype. In adenohypophysial cells dispersed in vitro ANG II (10(-8) M) released prolactin. Losartan (10(-7) and 10(-6) M), but not PD-123319, inhibited this effect. We conclude that in intact hypophyses of 15-day-old female rats the effect of LHRH on prolactin release is readily demonstrated. LHRH-induced prolactin release appears to be mediated by ANG II acting in a paracrine manner on AT1 receptors located on lactotrophs.

Valsartan independent of AT1 receptor inhibits tissue factor, TLR-2 and-4 expression by regulation of Egr-1 through activation of AMPK in diabetic conditions

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Ha, Yu Mi; Park, Eun Jung; Kang, Young Jin; Park, Sang Won; Kim, Hye Jung; Chang, Ki Churl

2014-01-01

Patients suffering from diabetes mellitus (DM) are at a severe risk of atherothrombosis. Early growth response (Egr)-1 is well characterized as a central mediator in vascular pathophysiology. We tested whether valsartan independent of Ang II type 1 receptor (AT1R) can reduce tissue factor (TF) and toll-like receptor (TLR)-2 and-4 by regulating Egr-1 in THP-1 cells and aorta in streptozotocin-induced diabetic mice. High glucose (HG, 15 mM) increased expressions of Egr-1, TF, TLR-2 and-4 which were significantly reduced by valsartan. HG increased Egr-1 expression by activation of PKC and ERK1/2 in THP-1 cells. Valsartan increased AMPK phosphorylation in a concentration and time-dependent manner via activation of LKB1. Valsartan inhibited Egr-1 without activation of PKC or ERK1/2. The reduced expression of Egr-1 by valsartan was reversed by either silencing Egr-1, or compound C, or DN-AMPK-transfected cells. Valsartan inhibited binding of NF-κB and Egr-1 to TF promoter in HG condition. Furthermore, valsartan reduced inflammatory cytokine (TNF-α, IL-6 and IL-1β) production and NF-κB activity in HG-activated THP-1 cells. Interestingly, these effects of valsartan were not affected by either silencing AT1R in THP-1 cells or CHO cells, which were devoid of AT1R. Importantly, administration of valsartan (20 mg/kg, i.p) for 8 weeks significantly reduced plasma TF activity, expression of Egr-1, TLR-2,-4 and TF in thoracic aorta and improved glucose tolerance of streptozotocin-induced diabetic mice. Taken together, we concluded that valsartan may reduce atherothrombosis in diabetic conditions through AMPK/Egr-1 regulation. PMID:25109475

Prolactin-inducible proteins in human breast cancer cells

International Nuclear Information System (INIS)

Shiu, R.P.; Iwasiow, B.M.

1985-01-01

The mechanism of action of prolactin in target cells and the role of prolactin in human breast cancer are poorly understood phenomena. The present study examines the effect of human prolactin (hPRL) on the synthesis of unique proteins by a human breast cancer cell line, T-47D, in serum-free medium containing bovine serum albumin. [ 35 S]Methionine-labeled proteins were analysed by sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis and fluorography. Treatment of cells with hPRL (1-1000 ng/ml) and hydrocortisone (1 microgram/ml) for 36 h or longer resulted in the synthesis and secretion of three proteins having molecular weights of 11,000, 14,000, and 16,000. Neither hPRL nor hydrocortisone alone induced these proteins. Of several other peptide hormones tested, only human growth hormone, a hormone structurally and functionally similar to hPRL, could replace hPRL in causing protein induction. These three proteins were, therefore, referred to as prolactin-inducible proteins (PIP). Each of the three PIPs was purified to homogeneity by preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and specific antibodies were generated to them in rabbits. By immunoprecipitation and immunoblotting (Western blot) of proteins secreted by T-47D cells, it was demonstrated that the three PIPs were immunologically identical to one another. In addition, the 16-kDa and 14-kDa proteins (PIP-16 and PIP-14), and not the 11-kDa protein (PIP-11), incorporated [ 3 H]glycosamine. Furthermore, 2-deoxyglucose (2 mM) and tunicamycin (0.5 micrograms/ml), two compounds known to inhibit glycosylation, blocked the production of PIP-16 and PIP-14, with a concomitant increase in the accumulation of PIP-11

Atherogenic ω-6 Lipids Modulate PPAR- EGR-1 Crosstalk in Vascular Cells

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Jia Fei

2011-01-01

Full Text Available Atherogenic ω-6 lipids are physiological ligands of peroxisome proliferator-activated receptors (PPARs and elicit pro- and antiatherogenic responses in vascular cells. The objective of this study was to investigate if ω-6 lipids modulated the early growth response-1 (Egr-1/PPAR crosstalk thereby altering vascular function. Rat aortic smooth muscle cells (RASMCs were exposed to ω-6 lipids, linoleic acid (LA, or its oxidized form, 13-HPODE (OxLA in the presence or absence of a PPARα antagonist (MK886 or PPARγ antagonist (GW9662 or PPAR-specific siRNA. Our results demonstrate that ω-6 lipids, induced Egr-1 and monocyte chemotactic protein-1 (MCP-1 mRNA and protein levels at the acute phase (1–4 hrs when PPARα was downregulated and at subacute phase (4–12 hrs by modulating PPARγ, thus resulting in altered monocyte adhesion to RASMCs. We provide novel insights into the mechanism of action of ω-6 lipids on Egr-1/PPAR interactions in vascular cells and their potential in altering vascular function.

Prolactin induces adrenal hypertrophy

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E.J. Silva

2004-02-01

Full Text Available Although adrenocorticotropic hormone is generally considered to play a major role in the regulation of adrenal glucocorticoid secretion, several reports have suggested that other pituitary hormones (e.g., prolactin also play a significant role in the regulation of adrenal function. The aim of the present study was to measure the adrenocortical cell area and to determine the effects of the transition from the prepubertal to the postpubertal period on the hyperprolactinemic state induced by domperidone (4.0 mg kg-1 day-1, sc. In hyperprolactinemic adult and young rats, the adrenals were heavier, as determined at necropsy, than in the respective controls: adults (30 days: 0.16 ± 0.008 and 0.11 ± 0.007; 46 days: 0.17 ± 0.006 and 0.12 ± 0.008, and 61 days: 0.17 ± 0.008 and 0.10 ± 0.004 mg for treated and control animals, respectively; P < 0.05, and young rats (30 days: 0.19 ± 0.003 and 0.16 ± 0.007, and 60 days: 0.16 ± 0.006 and 0.13 ± 0.009 mg; P < 0.05. We selected randomly a circular area in which we counted the nuclei of adrenocortical cells. The area of zona fasciculata cells was increased in hyperprolactinemic adult and young rats compared to controls: adults: (61 days: 524.90 ± 47.85 and 244.84 ± 9.03 µm² for treated and control animals, respectively; P < 0.05, and young rats: (15 days: 462.30 ± 16.24 and 414.28 ± 18.19; 60 days: 640.51 ± 12.91 and 480.24 ± 22.79 µm²; P < 0.05. Based on these data we conclude that the increase in adrenal weight observed in the hyperprolactinemic animals may be due to prolactin-induced adrenocortical cell hypertrophy.

Involvement of arachidonate metabolism in neurotensin-induced prolactin release in vitro

International Nuclear Information System (INIS)

Canonico, P.L.; Speciale, C.; Sortino, M.A.; Scapagnini, U.

1985-01-01

Neurotensin increased in a concentration-dependent manner the level of hypophyseal [ 3 H]arachidonic acid in vitro as well as prolactin release from hemipituitary glands. The effect of 1 microM neurotensin on arachidonate release was already present at 2.5 min, maximal at 5, and disappeared after a 10-min incubation. Neurotensin analogues produced an enhancement of hypophyseal arachidonate similar to their relative potencies in other cellular systems, whereas other peptides (somatostatin and vasoactive intestinal peptide) were devoid of any effect on the concentration of the fatty acid in the pituitary. Seventy micromoles RHC 80267, a rather selective inhibitor of diacylglycerol lipase, completely prevented the neurotensin-stimulated prolactin release and decreased arachidonate release both in basal or in neurotensin-induced conditions. Similar results were obtained with 50 microM quinacrine, a phospholipase A2 inhibitor. To clarify whether arachidonate released by neurotensin requires a further metabolism through specific pathways to stimulate prolactin release, the authors used indomethacin and BW 755c, two blockers of cyclooxygenase and lipoxygenase pathways. Thirty micromoles indomethacin, a dose active to inhibit cyclooxygenase, did not affect unesterified arachidonate levels either in basal or in neurotensin-induced conditions; moreover, the drug did not modify basal prolactin release but slightly potentiated the stimulatory effect of neurotensin on the release of the hormone. On the other hand, 250 microM BW 755c, an inhibitor of both cyclooxygenase and lipoxygenase pathways, significantly inhibited both basal and neurotensin-stimulated prolactin release and further potentiated the increase of the fatty acid concentrations produced by 1 microM neurotensin

Role of alveolar epithelial Early growth response-1 (Egr-1) in CD8+ T Cell mediated Lung Injury

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Ramana, Chilakamarti V.; Cheng, Guang-Shing; Kumar, Aseem; Kwon, Hyung- Joo; Enelow, Richard I.

2009-01-01

Influenza infection of the distal airways results in severe lung injury, a considerable portion of which is immunopathologic and attributable to the host responses. We have used a mouse model to specifically investigate the role of antiviral CD8+ T cells in this injury, and have found that the critical effector molecule is TNF-α expressed by the T cells upon antigen recognition. Interestingly, the immunopathology which ensues is characterized by significant accumulation of host inflammatory cells, recruited by chemokines expressed by the target alveolar epithelial cells. In this study we analyzed the mechanisms involved in the induction of epithelial chemokine expression triggered by antigen-specific CD8+ T cell recognition, and demonstrate that the Early growth response-1 (Egr-1) transcription factor is rapidly induced in epithelial cells, both in vitro and ex vivo, and that this is a critical regulator of a host of inflammatory chemokines. Genetic deficiency of Egr-1 significantly abrogates both the chemokine expression and the immunopathologic injury associated with T cell recognition, and it directly regulates transcriptional activity of a model CXC chemokine, MIP-2. We further demonstrate that Egr-1 induction is triggered by TNF-α– dependent ERK activation, and inhibition of this pathway ablates Egr-1 expression. These findings suggest that Egr-1 may represent an important target in mitigating the immunopathology of severe influenza infection. PMID:19786304

Role of alveolar epithelial early growth response-1 (Egr-1) in CD8+ T cell-mediated lung injury.

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Ramana, Chilakamarti V; Cheng, Guang-Shing; Kumar, Aseem; Kwon, Hyung-Joo; Enelow, Richard I

2009-12-01

Influenza infection of the distal airways results in severe lung injury, a considerable portion of which is immunopathologic and attributable to the host responses. We have used a mouse model to specifically investigate the role of antiviral CD8(+) T cells in this injury, and have found that the critical effector molecule is TNF-alpha expressed by the T cells upon antigen recognition. Interestingly, the immunopathology which ensues is characterized by significant accumulation of host inflammatory cells, recruited by chemokines expressed by the target alveolar epithelial cells. In this study we analyzed the mechanisms involved in the induction of epithelial chemokine expression triggered by antigen-specific CD8(+) T cell recognition, and demonstrate that the early growth response-1 (Egr-1) transcription factor is rapidly induced in epithelial cells, both in vitro and ex vivo, and that this is a critical regulator of a host of inflammatory chemokines. Genetic deficiency of Egr-1 significantly abrogates both the chemokine expression and the immunopathologic injury associated with T cell recognition, and it directly regulates transcriptional activity of a model CXC chemokine, MIP-2. We further demonstrate that Egr-1 induction is triggered by TNF-alpha-dependent ERK activation, and inhibition of this pathway ablates Egr-1 expression. These findings suggest that Egr-1 may represent an important target in mitigating the immunopathology of severe influenza infection.

pEgr-sTRAIL transfer in combination with 60Co γ ray irradiation to induce the apoptosis on HeLa cells and activation of Caspase-3

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Tian Mei; Guo Zhiying; Zhao Baofeng; Ruan Jianlei; Su Xu

2009-01-01

In order to approach the radiosensitivity of TRAIL expression controlled by Egr-1 promotor, the recombinant vector pEgr-sTRAIL was tranfected into HeLa cells, the early apoptosis and Caspase-3 activity were detected after different doses of 60 Co γ-ray irradiation. The results showed that pEgr-sTRAIL transfected in combination with γ-ray irradiation could significantly induce the apoptosis of HeLa cells in a dose-dependent manner. The higher activity of Capase-3 was also found in pEgr-sTRAIL irradiated group by using western blotting and spectrophotometry. Our result demonstrated that the activity of Caspase-3, as the apoptosis executor, play an important role in TRAIL-induced apoptosis and the enhanced TRAIL-induced apoptosis in transfected cells after irradiation can be controlled by radio-sensitive promoter Egr-1. (authors)

File list: Oth.Bld.10.Egr1.AllCell [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.Bld.10.Egr1.AllCell mm9 TFs and others Egr1 Blood SRX122513,SRX122511,SRX122510...,SRX122512 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Bld.10.Egr1.AllCell.bed ...

File list: Oth.Bld.05.Egr1.AllCell [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.Bld.05.Egr1.AllCell mm9 TFs and others Egr1 Blood SRX122511,SRX122510,SRX122512...,SRX122513 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Bld.05.Egr1.AllCell.bed ...

Regulation of tissue factor and inflammatory mediators by Egr-1 in a mouse endotoxemia model.

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Pawlinski, Rafal; Pedersen, Brian; Kehrle, Bettina; Aird, William C; Frank, Rolf D; Guha, Mausumee; Mackman, Nigel

2003-05-15

In septic shock, tissue factor (TF) activates blood coagulation, and cytokines and chemokines orchestrate an inflammatory response. In this study, the role of Egr-1 in lipopolysaccharide (LPS) induction of TF and inflammatory mediators in vivo was evaluated using Egr-1(+/+) and Egr-1(-/-) mice. Administration of LPS transiently increased the steady-state levels of Egr-1 mRNA in the kidneys and lungs of Egr-1(+/+) mice with maximal induction at one hour. Egr-1 was expressed in epithelial cells in the kidneys and lungs in untreated and LPS-treated mice. LPS induction of monocyte chemoattractant protein mRNA in the kidneys and lungs of Egr-1(-/-) mice was not affected at 3 hours, but its expression was significantly reduced at 8 hours compared with the expression observed in Egr-1(+/+) mice. Similarly, LPS induction of TF mRNA expression in the kidneys and lungs at 8 hours was reduced in Egr-1(-/-) mice. However, Egr-1 deficiency did not affect plasma levels of tumor necrosis factor alpha in endotoxemic mice. Moreover, Egr-1(+/+) and Egr-1(-/-) mice exhibited similar survival times in a model of acute endotoxemia. These data indicate that Egr-1 does not contribute to the early inflammatory response in the kidneys and lungs or the early systemic inflammatory response in endotoxemic mice. However, Egr-1 does contribute to the sustained expression of inflammatory mediators and to the maximal expression of TF at 8 hours in the kidneys and lungs.

File list: Oth.ALL.50.Egr1.AllCell [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.ALL.50.Egr1.AllCell mm9 TFs and others Egr1 All cell types SRX204724,SRX122513,...SRX122511,SRX122510,SRX122512 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.ALL.50.Egr1.AllCell.bed ...

Egr-1 and serum response factor are involved in growth factors- and serum-mediated induction of E2-EPF UCP expression that regulates the VHL-HIF pathway.

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Lim, Jung Hwa; Jung, Cho-Rok; Lee, Chan-Hee; Im, Dong-Soo

2008-11-01

E2-EPF ubiquitin carrier protein (UCP) has been shown to be highly expressed in common human cancers and target von Hippel-Lindau (VHL) for proteosomal degradation in cells, thereby stabilizing hypoxia-inducible factor (HIF)-1alpha. Here, we investigated cellular factors that regulate the expression of UCP gene. Promoter deletion assay identified binding sites for early growth response-1 (Egr-1) and serum response factor (SRF) in the UCP promoter. Hepatocyte or epidermal growth factor (EGF), or phorbol 12-myristate 13-acetate induced UCP expression following early induction of Egr-1 expression in HeLa cells. Serum increased mRNA and protein levels of SRF and UCP in the cell. By electrophoretic mobility shift and chromatin immunoprecipitation assays, sequence-specific DNA-binding of Egr-1 and SRF to the UCP promoter was detected in nuclear extracts from HeLa cells treated with EGF and serum, respectively. Overexpression of Egr-1 or SRF increased UCP expression. RNA interference-mediated depletion of endogenous Egr-1 or SRF impaired EGF- or serum-mediated induction of UCP expression, which was required for cancer cell proliferation. Systemic delivery of EGF into mice also increased UCP expression following early induction of Egr-1 expression in mouse liver. The induced UCP expression by the growth factors or serum increased HIF-1alpha protein level under non-hypoxic conditions, suggesting that the Egr-1/SRF-UCP-VHL pathway is in part responsible for the increased HIF-1alpha protein level in vitro and in vivo. Thus, growth factors and serum induce expression of Egr-1 and SRF, respectively, which in turn induces UCP expression that positively regulates cancer cell growth.

The immediate early gene product EGR1 and polycomb group proteins interact in epigenetic programming during chondrogenesis.

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Frank Spaapen

Full Text Available Initiation of and progression through chondrogenesis is driven by changes in the cellular microenvironment. At the onset of chondrogenesis, resting mesenchymal stem cells are mobilized in vivo and a complex, step-wise chondrogenic differentiation program is initiated. Differentiation requires coordinated transcriptomic reprogramming and increased progenitor proliferation; both processes require chromatin remodeling. The nature of early molecular responses that relay differentiation signals to chromatin is poorly understood. We here show that immediate early genes are rapidly and transiently induced in response to differentiation stimuli in vitro. Functional ablation of the immediate early factor EGR1 severely deregulates expression of key chondrogenic control genes at the onset of differentiation. In addition, differentiating cells accumulate DNA damage, activate a DNA damage response and undergo a cell cycle arrest and prevent differentiation associated hyper-proliferation. Failed differentiation in the absence of EGR1 affects global acetylation and terminates in overall histone hypermethylation. We report novel molecular connections between EGR1 and Polycomb Group function: Polycomb associated histone H3 lysine27 trimethylation (H3K27me3 blocks chromatin access of EGR1. In addition, EGR1 ablation results in abnormal Ezh2 and Bmi1 expression. Consistent with this functional interaction, we identify a number of co-regulated targets genes in a chondrogenic gene network. We here describe an important role for EGR1 in early chondrogenic epigenetic programming to accommodate early gene-environment interactions in chondrogenesis.

Valsartan independent of AT₁ receptor inhibits tissue factor, TLR-2 and -4 expression by regulation of Egr-1 through activation of AMPK in diabetic conditions.

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Ha, Yu Mi; Park, Eun Jung; Kang, Young Jin; Park, Sang Won; Kim, Hye Jung; Chang, Ki Churl

2014-10-01

Patients suffering from diabetes mellitus (DM) are at a severe risk of atherothrombosis. Early growth response (Egr)-1 is well characterized as a central mediator in vascular pathophysiology. We tested whether valsartan independent of Ang II type 1 receptor (AT1R) can reduce tissue factor (TF) and toll-like receptor (TLR)-2 and -4 by regulating Egr-1 in THP-1 cells and aorta in streptozotocin-induced diabetic mice. High glucose (HG, 15 mM) increased expressions of Egr-1, TF, TLR-2 and -4 which were significantly reduced by valsartan. HG increased Egr-1 expression by activation of PKC and ERK1/2 in THP-1 cells. Valsartan increased AMPK phosphorylation in a concentration and time-dependent manner via activation of LKB1. Valsartan inhibited Egr-1 without activation of PKC or ERK1/2. The reduced expression of Egr-1 by valsartan was reversed by either silencing Egr-1, or compound C, or DN-AMPK-transfected cells. Valsartan inhibited binding of NF-κB and Egr-1 to TF promoter in HG condition. Furthermore, valsartan reduced inflammatory cytokine (TNF-α, IL-6 and IL-1β) production and NF-κB activity in HG-activated THP-1 cells. Interestingly, these effects of valsartan were not affected by either silencing AT1R in THP-1 cells or CHO cells, which were devoid of AT1R. Importantly, administration of valsartan (20 mg/kg, i.p) for 8 weeks significantly reduced plasma TF activity, expression of Egr-1, TLR-2, -4 and TF in thoracic aorta and improved glucose tolerance of streptozotocin-induced diabetic mice. Taken together, we concluded that valsartan may reduce atherothrombosis in diabetic conditions through AMPK/Egr-1 regulation. © 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Different serotonin receptor types participate in 5-hydroxytryptophan-induced gonadotropins and prolactin release in the female infantile rat.

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Lacau-Mengido, I M; Libertun, C; Becú-Villalobos, D

1996-05-01

Serotonin (5-HT) receptors can be classified into at least three, possibly up to seven, classes of receptors. They comprise the 5-HT1, 5-HT2, and 5-HT3 classes, the "uncloned' 5-HT4 receptor and the recombinant receptors 5-ht5, 5-ht6 and 5-ht7. We investigated the role of different serotonin receptor types in a neuroendocrine response to the activation of the serotonergic system. Female immature rats were chosen as an experimental model as it has been shown that during the 3rd week of life, and not at later developmental stages, 5-hydroxytryptophan (5-HTP, a serotonin precursor) induces gonadotropin release in females and not in males. Besides, at this age, serotonin releases prolactin in both sexes. 5-HTP (50 mg/kg) released prolactin, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) as expected. Ketanserin (5-HT2A antagonist) and methysergide (5-HT2C antagonist) blocked 5-HTP-induced prolactin release, but did not block the LH or FSH responses. Ondansetron (5-HT3 receptor antagonist) did not modify prolactin response to 5-HTP, whereas it blocked 5-HTP-induced LH and FSH release. Propranolol (5-HT1 and beta-adrenergic antagonist) blocked prolactin, LH and FSH release induced by 5-HTP. The 5-HT2C agonist 1-(3-chlorophenyl)piperazine dihydrochloride released prolactin, without modifying LH or FSH release. Methyl-quipazine and phenylbiguanide (5-HT3 agonists) increased both LH and FSH levels, without altering prolactin secretion. The present experiments indicate that serotonin acting at the 5-HT3 receptor mediates LH and FSH release in infantile female rats, whereas 5-HT2C or 2A receptor types participate in the release of prolactin at this age. 5-HT1 receptor type may be involved in the release of the three hormones, though a beta-adrenergic component of the response cannot be discarded.

An Evaluation on Transfection Efficiency of pHRE-Egr1-EGFP in Hepatocellular Carcinoma Cells Bel-7402 Mediated by PEI-MZF-NPs

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Mei Lin

2011-01-01

Full Text Available To improve transfection and expression efficiency of target gene, especially under cancer anoxic microenvironment, we have developed pHRE-Egr1-EGFP/PEI-MZF-NPs nanosystem, in which pHRE-Egr1-EGFP, eukaryotic gene expression plasmid, is constructed by combining radiation promoter Egr1 with anoxia induction components (HRE, forming anoxic radiation double sensitive HRE/Egr1 promoter to activate reporter gene EGFP expression. MZF-NPs (Mn0.5 Zn0.5 Fe2O4 magnetic nanoparticles, obtained by coprecipitation method, are coated with cation poly(ethylenimine (PEI. We transferred pHRE-Egr1-EGFP into hepatocellular carcinoma Bel-7402 cells, using PEI-MZF-NPs as the carrier and tested some relevant efficacy. The results show that PEI-MZF-NPs have good DNA-binding ability, protection ability, release ability, little toxicity, and high transfection efficiency, obviously superior to those of the liposome method and electricity perforation method. Moreover, the expression level of EGFP gene induced by anoxia and radiation was significantly higher than that of single radiation activation. It is therefore concluded that HRE/Egr1 can induce and improve target gene expression efficiency in cancer anoxic microenvironment, and that PEI-MZF-NPs can be used as a novel nonviral gene vector which offers a viable approach to the mediated radiation gene therapy of cancer.

γ-Oryzanol suppresses COX-2 expression by inhibiting reactive oxygen species-mediated Erk1/2 and Egr-1 signaling in LPS-stimulated RAW264.7 macrophages.

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Shin, Soon Young; Kim, Heon-Woong; Jang, Hwan-Hee; Hwang, Yu-Jin; Choe, Jeong-Sook; Kim, Jung-Bong; Lim, Yoongho; Lee, Young Han

2017-09-16

Cyclooxygenase (COX)-2 produces prostanoids, which contribute to inflammatory responses. Nuclear factor (NF)-κB is a key transcription factor mediating COX-2 expression. γ-Oryzanol is an active component in rice bran oil, which inhibits lipopolysaccharide (LPS)-mediated COX-2 expression by inhibiting NF-κB. However, the inhibition of COX-2 expression by γ-oryzanol independently of NF-κB is poorly understood. We found that LPS upregulated Egr-1 expression at the transcriptional level. Forced expression of Egr-1 trans-activated the Cox-2 promoter independently of NF-κB. In contrast, silencing of Egr-1 abrogated LPS-mediated COX-2 expression. LPS produced reactive oxygen species (ROS), which, in turn, induced Egr-1 expression via the Erk1/2 MAPK pathway. ROS scavenging activity of γ-oryzanol suppressed Egr-1 expression by inhibiting the Erk1/2 MAPK pathway. Our results suggest that γ-oryzanol inhibits LPS-mediated COX-2 expression by suppressing Erk1/2-mediated Egr-1 expression. This study supports that γ-oryzanol may be useful for ameliorating LPS-mediated inflammatory responses. Copyright © 2017 Elsevier Inc. All rights reserved.

Interactions between prolactin and kisspeptin to control reproduction.

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Donato, Jose; Frazão, Renata

2016-01-01

Prolactin is best known for its effects of stimulating mammary gland development and lactogenesis. However, prolactin is a pleiotropic hormone that is able to affect several physiological functions, including fertility. Prolactin receptors (PRLRs) are widely expressed in several tissues, including several brain regions and reproductive tract organs. Upon activation, PRLRs may exert prolactin's functions through several signaling pathways, although the recruitment of the signal transducer and activator of transcription 5 causes most of the known effects of prolactin. Pathological hyperprolactinemia is mainly due to the presence of a prolactinoma or pharmacological effects induced by drugs that interact with the dopamine system. Notably, hyperprolactinemia is a frequent cause of reproductive dysfunction and may lead to infertility in males and females. Recently, several studies have indicated that prolactin may modulate the reproductive axis by acting on specific populations of hypothalamic neurons that express the Kiss1 gene. The Kiss1 gene encodes neuropeptides known as kisspeptins, which are powerful activators of gonadotropin-releasing hormone neurons. In the present review, we will summarize the current knowledge about prolactin's actions on reproduction. Among other aspects, we will discuss whether the interaction between prolactin and the Kiss1-expressing neurons can affect reproduction and how kisspeptins may become a novel therapeutic approach to treat prolactin-induced infertility.

Feasibility of a novel positive feedback effect of 131I-promoted Bac-Egr1-hNIS expression in malignant glioma via baculovirus

International Nuclear Information System (INIS)

Guo Rui; Tian Lipeng; Han Bing; Xu Haoping; Zhang Miao; Li Biao

2011-01-01

Purpose: As intracellular iodine is released rapidly, increased expression of sodium/iodide symporter (NIS) is required for effective radioiodine treatment of tumor. As Egr1 promoter is activated by 131 I and may promote human NIS (hNIS) expression, hNIS also induces 131 I uptake and activates Egr1, so the existence of a positive feedback effect of 131 I-promoted Egr1-hNIS expression is possible. Our purpose was to investigate the possible existence of this positive feedback effect through a series of in vitro pioneer studies. Method: Recombinant baculovirus (Bac-Egr1-hNIS) encoding the hNIS gene under the control of a radiation-inducible Egrl promoter was constructed. To test 131 I-promoted hNIS expression, human malignant glioma U87 cells were transfected with Bac-Egr1-hNIS, stimulated with or without 131 I; the expression of hNIS protein was detected by immunofluorescence and flow cytometry test. In addition, the uptake and efflux of 131 I were determined after the incubation of Bac-Egr1-hNIS-transfected U87 cells with or without 131 I. Results: Immunocytochemical staining and flow cytometry test showed a higher hNIS protein expression in Bac-Egr1-hNIS-transfected U87 cells with 131 I stimulation than in cells without stimulation. Bac-Egr1-hNIS-transfected U87 cells accumulated up to about 4.05 times of 131 I after 131 I stimulation. The amount of 131 I uptake in both groups showed a baculovirus dose-dependent manner. However, rapid efflux of radioactivity was observed in both groups, with 50% lost during the first 2 min after the 131 I-containing medium had been replaced by a nonradioactive medium. Conclusion: Our results indicated that an improved transgene expression of 131 I-stimulated hNIS in U87 cells using a baculovirus vector containing the Egr1 promoter is possible, and the increased expression of hNIS is responsible for a higher 131 I uptake. It might provide a reference for the existence of a positive feedback effect in 131 I-promoted Bac-Egr1-h

Egr2 enhances insulin resistance via JAK2/STAT3/SOCS-1 pathway in HepG2 cells treated with palmitate.

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Lu, Lin; Ye, Xinhua; Yao, Qing; Lu, Aijiao; Zhao, Zhen; Ding, Yang; Meng, Chuchen; Yu, Wenlong; Du, Yunfeng; Cheng, JinLuo

2018-05-01

Insulin resistance is generally responsible for the pathogenesis of type 2 diabetes mellitus (T2DM). Early growth response proteins-2 (Egr2) has been reported to be able to increase the expression of the suppressors of cytokine signaling-1 (SOCS-1), and impair insulin signaling pathway through suppression of insulin receptor substrates (IRS), including IRS-1 and IRS-2. However, whether Egr2 is directly involved in the development of insulin resistance, and how its potential contributions to insulin resistance still remain unknown. Here, our present investigation found that the expression levels of Egr2 were up-regulated when insulin resistance occurs, and knockdown of Egr2 abolished the effect of insulin resistance in HepG2 cells induced with palmitate (PA). Importantly, inhibition of Egr2 decreased the expression of SOCS-1 as well as reduced phosphorylation of JAK2 and STAT3. And, our data indicated that silencing of Egr2 accelerated hepatic glucose uptake and reversed the impaired lipid metabolism upon insulin resistance. In summary, the present study confirms that Egr2 could deteriorate insulin resistance via the pathway of JAK2/STAT3/SOCS-1 and may shed light on resolving insulin resistance and further the pathogenesis of T2DM. Copyright © 2017 Elsevier Inc. All rights reserved.

pH Modulates the Binding of EGR1 Transcription Factor to DNA

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Mikles, David C.; Bhat, Vikas; Schuchardt, Brett J.; Deegan, Brian J.; Seldeen, Kenneth L.; McDonald, Caleb B.; Farooq, Amjad

2013-01-01

EGR1 transcription factor orchestrates a plethora of signaling cascades involved in cellular homeostasis and its down-regulation has been implicated in the development of prostate cancer. Herein, using a battery of biophysical tools, we show that the binding of EGR1 to DNA is tightly regulated by solution pH. Importantly, the binding affinity undergoes an enhancement of more than an order of magnitude with increasing pH from 5 to 8, implying that the deprotonation of an ionizable residue accounts for such behavior. This ionizable residue is identified as H382 by virtue of the fact that its substitution to non-ionizable residues abolishes pH-dependence of the binding of EGR1 to DNA. Notably, H382 inserts into the major groove of DNA and stabilizes the EGR1-DNA interaction via both hydrogen bonding and van der Waals contacts. Remarkably, H382 is predominantly conserved across other members of EGR1 family, implying that histidine protonation-deprotonation may serve as a molecular switch for modulating protein-DNA interactions central to this family of transcription factors. Collectively, our findings uncover an unexpected but a key step in the molecular recognition of EGR1 family of transcription factors and suggest that they may act as sensors of pH within the intracellular environment. PMID:23718776

Paradoxical role of an Egr transcription factor family member, Egr2/Krox20, in learning and memory

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Roseline Poirier

2007-12-01

Full Text Available It is well established that Egr1/zif268, a member of the Egr family of transcription factors, is critical for the consolidation of several forms of memories. Recently, the Egr3 family member has also been implicated in learning and memory. Because Egr family members encode closely related zinc-finger transcription factors sharing a highly homologous DNA binding domain that recognises the same DNA sequence, they may have related functions in brain. Another Egr family member expressed in brain, Egr2/Krox20 is known to be crucial for normal hindbrain development and has been implicated in several inherited peripheral neuropathies; however, due to Egr2-null mice perinatal lethality, its potential role in cognitive functions in the adult has not been yet explored. Here, we generated Egr2 conditional mutant mice allowing postnatal, forebrain-specific Cre-mediated Egr2 excision and tested homozygous, heterozygous and control littermates on a battery of behavioural tasks to evaluate motor capacity, exploratory behaviour, emotional reactivity and learning and memory performance in spatial and non-spatial tasks. Egr2-deficient mice had no sign of locomotor, exploratory or anxiety disturbances. Surprisingly, they also had no impairment in spatial learning and memory, taste aversion memory or fear memory using a trace conditioning paradigm. On the contrary, Egr2-deficient mice had improved performance in motor learning on a rotarod, and in object recognition memory. These results clearly do not extend the phenotypic consequences resulting from either Egr1 or Egr3 loss-of-function to Egr2. In contrast, they indicate that Egr family members may have different, and in certain circumstances antagonistic functions in the adult brain.

Regulation of radiation-induced apoptosis by early growth response-1 gene in solid tumors

International Nuclear Information System (INIS)

Ahmed, M.

2003-01-01

Ionizing radiation exposure is associated with activation of certain immediate-early genes that function as transcription factors. These include members of jun or fos and early growth response (EGR) gene families. In particular, the functional role of EGR-1 in radiation-induced signaling is pivotal since the promoter of EGR-1 contains radiation-inducible CArG DNA sequences. The Egr-1 gene belongs to a family of Egr genes that includes EGR-2, EGR-3, EGR-4, EGR-α and the tumor suppressor, Wilms' tumor gene product, WT1. The Egr-1 gene product, EGR-1, is a nuclear protein that contains three zinc fingers of the C 2 H 2 subtype. The EGR-1 GC-rich consensus target sequence, 5'-GCGT/GGGGCG-3' or 5'-TCCT/ACCTCCTCC-3', has been identified in the promoter regions of transcription factors, growth factors, receptors, cell cycle regulators and pro-apoptotic genes. The gene targets mediated by Egr-1 in response to ionizing radiation include TNF-α , p53, Rb and Bax, all these are effectors of apoptosis. Based on these targets, Egr-1 is a pivotal gene that initiates early signal transduction events in response to ionizing radiation leading to either growth arrest or cell death in tumor cells. There are two potential application of Egr-1 gene in therapy of cancer. First, the Egr-1 promoter contains information for appropriate spatial and temporal expression in-vivo that can be regulated by ionizing radiation to control transcription of genes that have pro-apoptotic and suicidal function. Secondly, EGR-1 protein can eliminate 'induced-radiation resistance' by inhibiting the functions of radiation-induced pro-survival genes (NFκB activity and bcl-2 expression) and activate pro-apoptotic genes (such as bax) to confer a significant radio-sensitizing effect. Together, the reported findings from my laboratory demonstrate clearly that EGR-1 is an early central gene that confers radiation sensitivity and its pro-apoptotic functions are synergized by abrogation of induced radiation

Construction and expression of pEgr-sHemopexin recombinant plasmid induced by ionizing radiation in vitro

International Nuclear Information System (INIS)

Wang Guiquan; Jilin Univ., Changchun; Xu Chuanjie; Yang Wen; Piao Chunji; Dong Zhen

2005-01-01

Objective: To clone mouse secretable Hemopexin (sPEX) cDNA, construct pEgr-sPEX recombinant plasmid and detect the expression of recombinant plasmid in B16F10 cells. Methods: Hemopexin cDNA was amplified from the NIH3T3 cells by RT-PCR. After the cDNA identified by sequencing, the pEgr-sPEX recombinant plasmid was constructed and the plasmid was transfected into B16F10 cells with liposome and the expression of PEX induced by ionizing radiation in B16F10 cells was detected by Western blotting. Results: The sequencing results proved the cloned sPEX cDNA to be completely identical with that reported in the GenBank. The mouse sPEX cDNA was inserted correctly into expression vector and expressed successfully. Conclusion: The mouse sPEX cDNA is cloned successfully and it is confirmed that pEgr-sPEX possesses the radiation inducing expression characteristics in vitro. (authors)

Inhibition of cell growth by EGR-1 in human primary cultures from malignant glioma

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Gagliardi Franco

2004-01-01

Full Text Available Abstract Background The aim of this work was to investigate in vitro the putative role of EGR-1 in the growth of glioma cells. EGR-1 expression was examined during the early passages in vitro of 17 primary cell lines grown from 3 grade III and from 14 grade IV malignant astrocytoma explants. The explanted tumors were genetically characterized at the p53, MDM2 and INK4a/ARF loci, and fibronectin expression and growth characteristics were examined. A recombinant adenovirus overexpressing EGR-1 was tested in the primary cell lines. Results Low levels of EGR-1 protein were found in all primary cultures examined, with lower values present in grade IV tumors and in cultures carrying wild-type copies of p53 gene. The levels of EGR-1 protein were significantly correlated to the amount of intracellular fibronectin, but only in tumors carrying wild-type copies of the p53 gene (R = 0,78, p = 0.0082. Duplication time, plating efficiency, colony formation in agarose, and contact inhibition were also altered in the p53 mutated tumor cultures compared to those carrying wild-type p53. Growth arrest was achieved in both types of tumor within 1–2 weeks following infection with a recombinant adenovirus overexpressing EGR-1 but not with the control adenovirus. Conclusions Suppression of EGR-1 is a common event in gliomas and in most cases this is achieved through down-regulation of gene expression. Expression of EGR-1 by recombinant adenovirus infection almost completely abolishes the growth of tumor cells in vitro, regardless of the mutational status of the p53 gene.

Regulation of Peripheral Myelination through Transcriptional Buffering of Egr2 by an Antisense Long Non-coding RNA

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Margot Martinez-Moreno

2017-08-01

Full Text Available Precise regulation of Egr2 transcription is fundamentally important to the control of peripheral myelination. Here, we describe a long non-coding RNA antisense to the promoter of Egr2 (Egr2-AS-RNA. During peripheral nerve injury, the expression of Egr2-AS-RNA is increased and correlates with decreased Egr2 transcript and protein levels. Ectopic expression of Egr2-AS-RNA in dorsal root ganglion (DRG cultures inhibits the expression of Egr2 mRNA and induces demyelination. In vivo inhibition of Egr2-AS-RNA using oligonucleotide GapMers released from a biodegradable hydrogel following sciatic nerve injury reverts the EGR2-mediated gene expression profile and significantly delays demyelination. Egr2-AS-RNA gradually recruits H3K27ME3, AGO1, AGO2, and EZH2 on the Egr2 promoter following sciatic nerve injury. Furthermore, expression of Egr2-AS-RNA is regulated through ERK1/2 signaling to YY1, while loss of Ser184 of YY1 regulates binding to Egr2-AS-RNA. In conclusion, we describe functional exploration of an antisense long non-coding RNA in peripheral nervous system (PNS biology.

Study on construction of pEgr-hPTEN expression vector induced by irradiation and its anti-tumor effect in vitro

International Nuclear Information System (INIS)

Tian Mei; Jin Guanghui; Piao Chunji; Li Xiuyi; Liu Linlin

2003-01-01

Objective: To clone the cDNA of human tumor suppressor gene-PTEN, construct pEgr-hPTEN expression vector induced by irradiation and study its inhibitory effect on proliferation of malignant glioma cell line SHG-44 transfected steadily with pEgr-hPTEN after different doses of X-ray irradiation. Methods: A DNA fragment about 1200 bp, PTEN, was amplified from human placenta tissues by using RT-nested PCR and was cloned into pUCm-T vector after automatic sequencing, then the fragment was inserted into a vector pcD-NA3.1-Egr to construct an expression vector pEgr-hPTEN. pEgr-hPTEN was transfected into SHG-44 cells in vitro. Stably transfected cell line SHG-44-sPTEN was selected through G418. The inhibitor effect on SHG-44-sPTEN was observed after different doses of X-ray irradiation in vitro. Results: The PTEN cDNA has been cloned correctly and its expression vector pEgr-hPTEN was also constructed. Growth of SHG-44 cells was inhibited significantly by stable pEgr-hPTEN transfection combined with X-ray irradiation. With the increase of dose, the inhibitory effect was enhanced within 5 Gy. Conclusion: Human tumor suppressor gene-PTEN cDNA has been cloned and its expression vector has been constructed. The tumor was inhibited significantly by gene-radiotherapy in vitro. The result provides the theoretical and experimental basis for improvement of clinical radiotherapeutic effect on tumors

The transcription factor EGR1 localizes to the nucleolus and is linked to suppression of ribosomal precursor synthesis.

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Ponti, Donatella; Bellenchi, Gian Carlo; Puca, Rosa; Bastianelli, Daniela; Maroder, Marella; Ragona, Giuseppe; Roussel, Pascal; Thiry, Marc; Mercola, Dan; Calogero, Antonella

2014-01-01

EGR1 is an immediate early gene with a wide range of activities as transcription factor, spanning from regulation of cell growth to differentiation. Numerous studies show that EGR1 either promotes the proliferation of stimulated cells or suppresses the tumorigenic growth of transformed cells. Upon interaction with ARF, EGR1 is sumoylated and acquires the ability to bind to specific targets such as PTEN and in turn to regulate cell growth. ARF is mainly localized to the periphery of nucleolus where is able to negatively regulate ribosome biogenesis. Since EGR1 colocalizes with ARF under IGF-1 stimulation we asked the question of whether EGR1 also relocate to the nucleolus to interact with ARF. Here we show that EGR1 colocalizes with nucleolar markers such as fibrillarin and B23 in the presence of ARF. Western analysis of nucleolar extracts from HeLa cells was used to confirm the presence of EGR1 in the nucleolus mainly as the 100 kDa sumoylated form. We also show that the level of the ribosomal RNA precursor 47S is inversely correlated to the level of EGR1 transcripts. The EGR1 iseffective to regulate the synthesis of the 47S rRNA precursor. Then we demonstrated that EGR1 binds to the Upstream Binding Factor (UBF) leading us to hypothesize that the regulating activity of EGR1 is mediated by its interaction within the transcriptional complex of RNA polymerase I. These results confirm the presence of EGR1 in the nucleolus and point to a role for EGR1 in the control of nucleolar metabolism.

The transcription factor EGR1 localizes to the nucleolus and is linked to suppression of ribosomal precursor synthesis.

Directory of Open Access Journals (Sweden)

Donatella Ponti

Full Text Available EGR1 is an immediate early gene with a wide range of activities as transcription factor, spanning from regulation of cell growth to differentiation. Numerous studies show that EGR1 either promotes the proliferation of stimulated cells or suppresses the tumorigenic growth of transformed cells. Upon interaction with ARF, EGR1 is sumoylated and acquires the ability to bind to specific targets such as PTEN and in turn to regulate cell growth. ARF is mainly localized to the periphery of nucleolus where is able to negatively regulate ribosome biogenesis. Since EGR1 colocalizes with ARF under IGF-1 stimulation we asked the question of whether EGR1 also relocate to the nucleolus to interact with ARF. Here we show that EGR1 colocalizes with nucleolar markers such as fibrillarin and B23 in the presence of ARF. Western analysis of nucleolar extracts from HeLa cells was used to confirm the presence of EGR1 in the nucleolus mainly as the 100 kDa sumoylated form. We also show that the level of the ribosomal RNA precursor 47S is inversely correlated to the level of EGR1 transcripts. The EGR1 iseffective to regulate the synthesis of the 47S rRNA precursor. Then we demonstrated that EGR1 binds to the Upstream Binding Factor (UBF leading us to hypothesize that the regulating activity of EGR1 is mediated by its interaction within the transcriptional complex of RNA polymerase I. These results confirm the presence of EGR1 in the nucleolus and point to a role for EGR1 in the control of nucleolar metabolism.

Apelin-13 upregulates Egr-1 expression in rat vascular smooth muscle cells through the PI3K/Akt and PKC signaling pathways

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Liu, Qi-Feng [Department of Cardiology, The First Affiliated Hospital of Liaoning Medical University, Jinzhou 121001 (China); Yu, Hong-Wei [Department of Cardiology, Jinzhou Central Hospital, Jinzhou 121001 (China); Sun, Li-Li [Department of Ophthalmology, The Third Affiliated Hospital of Liaoning Medical University, Jinzhou 121001 (China); You, Lu; Tao, Gui-Zhou [Department of Cardiology, The First Affiliated Hospital of Liaoning Medical University, Jinzhou 121001 (China); Qu, Bao-Ze, E-mail: qubaoze1971@hotmail.com [Department of Cardiology, The First Affiliated Hospital of Liaoning Medical University, Jinzhou 121001 (China)

2015-12-25

Previous studies have shown that Apelin-13 upregulates early growth response factor-1 (Egr-1) via the extracellular signal-regulated protein kinase (ERK) signaling pathway. Apelin-13 induces proliferation and migration of vascular smooth muscle cells (VSMCs) as well as the upregulation of osteopontin (OPN) via the upregulation of Egr-1. This study was designed to further explore the activity of Apelin-13 in VSMCs by investigating members of the mitogen-activated protein kinase (MAPK) family, in particular Jun kinase (JNK) and p38 mitogen-activated protein kinase (P38). We also examined whether the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) and protein kinase C (PKC) signaling pathways were involved in the regulation of Egr-1 by Apelin-13. We treated rat aortic VSMCs with Apelin-13 and examined the expression of JNK, p-JNK, P38, and p-P38 to investigate whether Apelin-13-mediated increases in Egr-1 occurred through the JNK and P38 signaling pathways. We then pretreated VSMCs with the Gi protein inhibitor pertussis toxin (PTX) and the Gq inhibitor YM254890, added Apelin-13 and looked for changes in Egr-1 expression. Finally, we pretreated with the PI3K inhibitor LY294002 and the PKC inhibitor GF109203X, and treated with Apelin-13. Our results showed that JNK and P38 did not participate in Apelin-13-mediated increase in Egr-1. Instead, Apelin-13 upregulation of Egr-1 was mediated by a PTX-sensitive Gi protein. Apelin-13 did increase ERK phosphorylation through the PI3K/Akt and PKC signaling pathways, resulting in changes in Egr-1 expression. These data provide important targets for future studies to modulate vascular remodeling. - Highlights: • Apelin-13 mediates Egr-1 upregulation in vascular smooth muscle cells via ERK1/2. • The underlying mechanisms are unknown, but exclude Jnk or p38 pathway activation. • Apelin-13 binds to Gi, activating the PI3K/Akt and PKC signaling cascades. • Consequent ERK phosphorylation results in increased Egr-1

Apelin-13 upregulates Egr-1 expression in rat vascular smooth muscle cells through the PI3K/Akt and PKC signaling pathways

International Nuclear Information System (INIS)

Liu, Qi-Feng; Yu, Hong-Wei; Sun, Li-Li; You, Lu; Tao, Gui-Zhou; Qu, Bao-Ze

2015-01-01

Previous studies have shown that Apelin-13 upregulates early growth response factor-1 (Egr-1) via the extracellular signal-regulated protein kinase (ERK) signaling pathway. Apelin-13 induces proliferation and migration of vascular smooth muscle cells (VSMCs) as well as the upregulation of osteopontin (OPN) via the upregulation of Egr-1. This study was designed to further explore the activity of Apelin-13 in VSMCs by investigating members of the mitogen-activated protein kinase (MAPK) family, in particular Jun kinase (JNK) and p38 mitogen-activated protein kinase (P38). We also examined whether the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) and protein kinase C (PKC) signaling pathways were involved in the regulation of Egr-1 by Apelin-13. We treated rat aortic VSMCs with Apelin-13 and examined the expression of JNK, p-JNK, P38, and p-P38 to investigate whether Apelin-13-mediated increases in Egr-1 occurred through the JNK and P38 signaling pathways. We then pretreated VSMCs with the Gi protein inhibitor pertussis toxin (PTX) and the Gq inhibitor YM254890, added Apelin-13 and looked for changes in Egr-1 expression. Finally, we pretreated with the PI3K inhibitor LY294002 and the PKC inhibitor GF109203X, and treated with Apelin-13. Our results showed that JNK and P38 did not participate in Apelin-13-mediated increase in Egr-1. Instead, Apelin-13 upregulation of Egr-1 was mediated by a PTX-sensitive Gi protein. Apelin-13 did increase ERK phosphorylation through the PI3K/Akt and PKC signaling pathways, resulting in changes in Egr-1 expression. These data provide important targets for future studies to modulate vascular remodeling. - Highlights: • Apelin-13 mediates Egr-1 upregulation in vascular smooth muscle cells via ERK1/2. • The underlying mechanisms are unknown, but exclude Jnk or p38 pathway activation. • Apelin-13 binds to Gi, activating the PI3K/Akt and PKC signaling cascades. • Consequent ERK phosphorylation results in increased Egr-1

In vivo oestrogenic modulation of Egr1 and Pitx1 gene expression in female rat pituitary gland.

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Gajewska, Alina; Herman, Andrzej P; Wolińska-Witort, Ewa; Kochman, Kazimierz; Zwierzchowski, Lech

2014-12-01

EGR1 and PITX1 are transcription factors required for gonadotroph cell Lhb promoter activation. To determine changes in Egr1 and Pitx1 mRNA levels in central and peripheral pituitary stimulations, an in vivo model based on i.c.v. pulsatile (1 pulse/0.5 h over 2 h) GnRH agonist (1.5 nM buserelin) or antagonist (2 nM antide) microinjections was used. The microinjections were given to ovariectomised and 17β-oestradiol (E2) (3×20 μg), ERA (ESR1) agonist propyl pyrazole triol (PPT) (3×0.5 mg), ERB (ESR2) agonist diarylpropionitrile (DPN) (3×0.5 mg) s.c. pre-treated rats 30 min after last pulse anterior pituitaries were excised. Relative mRNA expression was determined by quantitative RT-PCR (qRT-PCR). Results revealed a gene-specific response for GnRH and/or oestrogenic stimulations in vivo. Buserelin pulses enhanced Egr1 expression by 66% in ovariectomised rats, whereas the oestradiol-supplemented+i.c.v. NaCl-microinjected group showed a 50% increase in Egr1 mRNA expression. The oestrogenic signal was transmitted via ERA (ESR1) and ERB (ESR2) activation as administration of PPT and DPN resulted in 97 and 62%, respectively, elevation in Egr1 mRNA expression. A synergistic action of GnRH agonist and 17β-oestradiol (E2) stimulation of the Egr1 gene transcription in vivo were found. GnRHR activity did not affect Pitx1 mRNA expression; regardless of NaCl, buserelin or antide i.c.v. pulses, s.c. oestrogenic supplementation (with E2, PPT or DPN) consistently decreased (by -46, -48 and -41% respectively) the Pitx1 mRNA in the anterior pituitary gland. Orchestrated Egr1 and Pitx1 activities depending on specific central and peripheral regulatory inputs could be responsible for physiologically variable Lhb gene promoter activation in vivo. © 2014 Society for Endocrinology.

Radioprotective effect of hematopoietic growth factor gene therapy regulated by Egr-1 promoter on radiation injury of SCID mice

International Nuclear Information System (INIS)

Du Nan; Pei Xuetao; Luo Chengji; Su Yongping; Cheng Tianmin

2002-01-01

Objective: To explore the radioprotective effect of the expression of hematopoietic growth factors regulated by radio-inducible promoter on radiation injury. Methods: The human FL cDNA and EGFP cDNA were linked together with an internal ribosome entry site (IRES) and then inserted into the eukaryotic expression vector pCI-neo with the Egr-1 promoter (Egr-EF), and further transduced into bone marrow stromal cell lines HFCL (HFCL/EF). The HFCL/EF and CD34 + cells from human umbilical cord blood were transplanted i.v. one after the other into sublethally irradiated severe combined immunodeficient (SCID) mice. The number of peripheral blood WBC and human cells engrafted in recipient mice were detected by flow cytometry and CFU-GM assay. Results: In contrast to two control groups (HFCL and HFCL/F), HFCL/EF (the Egr-1 regulatory element-driven expression of FL gene therapy) resulted in a proportionally obvious increase in the number of the WBC at early stage after irradiation. Significant differences were found for CD45 + , CD34 + , CFU-GM, and nucleated cells in the bone marrow. Conclusion: Hematopoietic growth factor gene therapy regulated by radio-inducible promoter has radioprotective effect on radiation hematopoietic injury

Inhibitory effects of recombinant plasmid pshuttle-Egr1-shTRAIL transfection in combination with X-irradiation on growth of liver cancer cells SMMC7721

International Nuclear Information System (INIS)

Chen Zhiyong; Liu Min; Dong Lihua; Gong Shouliang

2011-01-01

Objective: To investigate the effect of recombinant plasmid pshuttle-Egr1-shTRAIL stable transfection in combination with X-ray irradiation on the TRAIL protein expression and the apoptosis in human SMMC7721 hepatoma cells. Methods: The pshuttle-Egr1-shTRAIL packaged with liposome was stably transfected into SMMC7721 cells in vitro. The shTRAIL protein expression were measured with ELISA assay, Annexin V-FITC kit was adopted to measure the apoptosis of pshuttle-Egr1-shTRAIL cells, and the changes in survival rate of SMMC7721 cells measured with cell cloning assay. Results: The TRAIL protein expressions in pshuttle-Egr1-shTRAIL plus different doses of irradiation groups were significantly increased compared with 0 Gy group (P<0.001). The percentage of apoptotic cells was significantly higher than that in 0 Gy group (P<0.05 or P<0.001), and the survival rate of SMMC7721 cells was decreased significantly (P<0.05 or P<0.001). Conclusion: The pshuttle-Egr1-shTRAIL stable transfection in combination with irradiation can significantly induce the apoptosis of SMMC7721 tumor cells and inhibit the cell proliferation. (authors)

Egr-1 mediated cardiac miR-99 family expression diverges physiological hypertrophy from pathological hypertrophy.

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Ramasamy, Subbiah; Velmurugan, Ganesan; Rekha, Balakrishnan; Anusha, Sivakumar; Shanmugha Rajan, K; Shanmugarajan, Suresh; Ramprasath, Tharmarajan; Gopal, Pandi; Tomar, Dhanendra; Karthik, Karuppusamy V; Verma, Suresh Kumar; Garikipati, Venkata Naga Srikanth; Sudarsan, Rajan

2018-04-01

The physiological cardiac hypertrophy is an adaptive condition without myocyte cell death, while pathological hypertrophy is a maladaptive condition associated with myocyte cell death. This study explores the miRNome of α-2M-induced physiologically hypertrophied cardiomyocytes and the role of miRNA-99 family during cardiac hypertrophy. Physiological and pathological cardiac hypertrophy was induced in H9c2 cardiomyoblast cell lines using α-2M and isoproterenol respectively. Total RNA isolation and small RNA sequencing were executed for physiological hypertrophy model. The differentially expressed miRNAs and its target mRNAs were validated in animal models. Transcription factor binding sites were predicted in the promoter of specific miRNAs and validated by ChIP-PCR. Subsequently, the selected miRNA was functionally characterized by overexpression and silencing. The effects of silencing of upstream regulator and downstream target gene were studied. Analysis of small RNA reads revealed the differential expression of a large set of miRNAs during hypertrophy, of which miR-99 family was highly downregulated upon α-2M treatment. However, this miR-99 family expression was upregulated during pathological hypertrophy and confirmed in animal models. ChIP-PCR confirms the binding of Egr-1 transcription factor to the miR-99 promoter. Further, silencing of Egr-1 decreased the expression of miR-99. The overexpression or silencing of miR-99 diverges the physiological hypertrophy to pathological hypertrophy and vice versa by regulating Akt-1 pathway. Silencing of Akt-1 replicates the effect of overexpression of miR-99. The results proved Egr-1 mediated regulation of miR-99 family that plays a key role in determining the fate of cardiac hypertrophy by regulating Akt-1 signaling. Copyright © 2018 Elsevier Inc. All rights reserved.

Klotho down-regulates Egr-1 by inhibiting TGF-β1/Smad3 signaling in high glucose treated human mesangial cells

International Nuclear Information System (INIS)

Li, Yang; Hu, Fang; Xue, Meng; Jia, Yi-Jie; Zheng, Zong-Ji; Wang, Ling; Guan, Mei-Ping; Xue, Yao-Ming

2017-01-01

Diabetic kidney disease (DKD) has become the leading cause of end-stage renal disease worldwide and is associated with glomerular mesangial cell (MC) proliferation and excessive extracellular matrix (ECM) production. Klotho can attenuate renal fibrosis in part by inhibiting TGF-β1/Smad3 signaling in DKD. Early growth response factor 1 (Egr-1) has been shown to play a key role in renal fibrosis in part by facilitating the formation of a positive feedback loop involving TGF-β1. However, whether Klotho down-regulates Egr-1 by inhibiting TGF-β1/Smad3 signaling in DKD is unclear. In the present study, we assessed human MCs that were incubated under high-glucose conditions to mimic diabetes. Then, we transfected the cells with Klotho plasmid or siRNA to overexpress or knock down Klotho gene and protein expression. Klotho, Egr-1, fibronectin (FN), collagen type I (Col I), Smad3 and phosphorylated Smad3 (p-Smad3) gene and protein expression levels were determined by RT-qPCR and western blotting respectively. High glucose time-dependently down-regulated Klotho mRNA and protein expression in cultured human MCs. pcDNA3.1-Klotho transfection-mediated Klotho overexpression down-regulated Egr-1, FN and Col I expression and the p-Smad3/Smad3 ratio in human MCs. Conversely, siRNA-mediated Klotho silencing up-regulated Egr-1, FN, and Col I expression and the p-Smad3/Smad3 ratio. Moreover, the effects of si-Klotho on Egr-1 expression were abolished by the TGF-β1 inhibitor SB-431542. Klotho overexpression can prevent mesangial ECM production in high-glucose-treated human MCs, an effect that has been partially attributed to Egr-1 down-regulation facilitated by TGF-β1/Smad3 signaling inhibition. - Highlights: • High glucose time-dependently down-regulated Klotho mRNA and protein expression in cultured human MCs. • Klotho overexpression down-regulated Egr-1 and prevented mesangial ECM production in high-glucose-treated human MCs. • Klotho down-regulated Egr-1 by inhibiting

Prolactin-sensitive neurons express estrogen receptor-α and depend on sex hormones for normal responsiveness to prolactin.

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Furigo, Isadora C; Kim, Ki Woo; Nagaishi, Vanessa S; Ramos-Lobo, Angela M; de Alencar, Amanda; Pedroso, João A B; Metzger, Martin; Donato, Jose

2014-05-30

Estrogens and prolactin share important target tissues, including the gonads, brain, liver, kidneys and some types of cancer cells. Herein, we sought anatomical and functional evidence of possible crosstalk between prolactin and estrogens in the mouse brain. First, we determined the distribution of prolactin-responsive neurons that express the estrogen receptor α (ERα). A large number of prolactin-induced pSTAT5-immunoreactive neurons expressing ERα mRNA were observed in several brain areas, including the anteroventral periventricular nucleus, medial preoptic nucleus, arcuate nucleus of the hypothalamus, ventrolateral subdivision of the ventromedial nucleus of the hypothalamus (VMH), medial nucleus of the amygdala and nucleus of the solitary tract. However, although the medial preoptic area, periventricular nucleus of the hypothalamus, paraventricular nucleus of the hypothalamus, retrochiasmatic area, dorsomedial subdivision of the VMH, lateral hypothalamic area, dorsomedial nucleus of the hypothalamus and ventral premammillary nucleus contained significant numbers of prolactin-responsive neurons, these areas showed very few pSTAT5-immunoreactive cells expressing ERα mRNA. Second, we evaluated prolactin sensitivity in ovariectomized mice and observed that sex hormones are required for a normal responsiveness to prolactin as ovariectomized mice showed a lower number of prolactin-induced pSTAT5 immunoreactive neurons in all analyzed brain nuclei compared to gonad-intact females. In addition, we performed hypothalamic gene expression analyses to determine possible post-ovariectomy changes in components of prolactin signaling. We observed no significant changes in the mRNA expression of prolactin receptor, STAT5a or STAT5b. In summary, sex hormones exert a permissive role in maintaining the brain's prolactin sensitivity, most likely through post-transcriptional mechanisms. Copyright © 2014 Elsevier B.V. All rights reserved.

Dual‑sensitive HRE/Egr1 promoter regulates Smac overexpression and enhances radiation‑induced A549 human lung adenocarcinoma cell death under hypoxia.

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Li, Chang-Feng; Chen, Li-Bo; Li, Dan-Dan; Yang, Lei; Zhang, Bao-Gang; Jin, Jing-Peng; Zhang, Ying; Zhang, Bin

2014-08-01

The aim of this study was to construct an expression vector carrying the hypoxia/radiation dual‑sensitive chimeric hypoxia response element (HRE)/early growth response 1 (Egr‑1) promoter in order to overexpress the therapeutic second mitochondria‑derived activator of caspases (Smac). Using this expression vector, the present study aimed to explore the molecular mechanism underlying radiotherapy‑induced A549 human lung adenocarcinoma cell death and apoptosis under hypoxia. The plasmids, pcDNA3.1‑Egr1‑Smac (pE‑Smac) and pcDNA3.1‑HRE/Egr-1‑Smac (pH/E‑Smac), were constructed and transfected into A549 human lung adenocarcinoma cells using the liposome method. CoCl2 was used to chemically simulate hypoxia, followed by the administration of 2 Gy X‑ray irradiation. An MTT assay was performed to detect cell proliferation and an Annexin V‑fluorescein isothiocyanate apoptosis detection kit was used to detect apoptosis. Quantitative polymerase chain reaction and western blot analyses were used for the detection of mRNA and protein expression, respectively. Infection with the pE‑Smac and pH/E‑Smac plasmids in combination with radiation and/or hypoxia was observed to enhance the expression of Smac. Furthermore, Smac overexpression was found to enhance the radiation‑induced inhibition of cell proliferation and promotion of cycle arrest and apoptosis. The cytochrome c/caspase‑9/caspase‑3 pathway was identified to be involved in this regulation of apoptosis. Plasmid infection in combination with X‑ray irradiation was found to markedly induce cell death under hypoxia. In conclusion, the hypoxia/radiation dual‑sensitive chimeric HRE/Egr‑1 promoter was observed to enhance the expression of the therapeutic Smac, as well as enhance the radiation‑induced inhibition of cell proliferation and promotion of cycle arrest and apoptosis under hypoxia. This apoptosis was found to involve the mitochondrial pathway.

Analysis list: Egr2 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Egr2 Blood + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Egr2.1.tsv h...ttp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Egr2.5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Eg...r2.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Egr2.Blood.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Blood.gml ...

Histone Deacetylase Inhibitors Activate Tristetraprolin Expression through Induction of Early Growth Response Protein 1 (EGR1 in Colorectal Cancer Cells

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Cyril Sobolewski

2015-08-01

Full Text Available The RNA-binding protein tristetraprolin (TTP promotes rapid decay of mRNAs bearing 3' UTR AU-rich elements (ARE. In many cancer types, loss of TTP expression is observed allowing for stabilization of ARE-mRNAs and their pathologic overexpression. Here we demonstrate that histone deacetylase (HDAC inhibitors (Trichostatin A, SAHA and sodium butyrate promote TTP expression in colorectal cancer cells (HCA-7, HCT-116, Moser and SW480 cells and cervix carcinoma cells (HeLa. We found that HDAC inhibitors-induced TTP expression, promote the decay of COX-2 mRNA, and inhibit cancer cell proliferation. HDAC inhibitors were found to promote TTP transcription through activation of the transcription factor Early Growth Response protein 1 (EGR1. Altogether, our findings indicate that loss of TTP in tumors occurs through silencing of EGR1 and suggests a therapeutic approach to rescue TTP expression in colorectal cancer.

PROLACTIN-INDUCED TYROSINE PHOSPHORYLATION, ACTIVATION AND RECEPTOR ASSOCIATION OF FOCAL ADHESION KINASE (FAK) IN MAMMARY EPITHELIAL CELLS

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Prolactin-Induced Tyrosine Phosphorylation, Activation and ReceptorAssociation of Focal Adhesion Kinase (FAK) in Mammary Epithelial Cells. Suzanne E. Fenton1 and Lewis G. Sheffield2. 1U.S. Environmental ProtectionAgency, MD-72, Research Triangle Park, NC 27711, and

High frequency of tumor cells with nuclear Egr-1 protein expression in human bladder cancer is associated with disease progression

International Nuclear Information System (INIS)

Egerod, Frederikke Lihme; Bartels, Annette; Fristrup, Niels; Borre, Michael; Ørntoft, Torben F; Oleksiewicz, Martin B; Brünner, Nils; Dyrskjøt, Lars

2009-01-01

Egr-1 (early growth response-1 transcription factor) has been proposed to be involved in invasion and metastasis processes of human bladder cancer, but Egr-1 protein expression levels in human bladder cancer have not been investigated. In the present study we investigated the expression levels of Egr-1 protein in early stages of human bladder cancer and correlated it to later progression. Expression of Egr-1 protein in human bladder cancer was examined by immunohistochemistry, on a tissue microarray constructed from tumors from 289 patients with non-muscle invasive urothelial bladder cancer. The frequency of tumor cells with nuclear Egr-1 immunolabelling correlated to bladder cancer stage, grade and to later progression to muscle-invasive bladder cancer (T2-4). Stage T1 tumors exhibited significantly higher frequencies of tumor cells with nuclear Egr-1 immunolabelling than Ta tumors (P = 0.001). Furthermore, Kaplan-Meier survival analysis showed that a high frequency of tumor cells with nuclear Egr-1 immunolabelling was significantly associated with a higher risk of progression to stage T2-4 (log-rank test, P = 0.035). Tumor cells with nuclear Egr-1 immunolabelling were found to localize at the tumor front in some of the tumor biopsies. The results from this study support a potential involvement of Egr-1 in the progression from non-muscle invasive bladder cancers to muscle invasive bladder cancer

Regulatory role of melatonin and BMP-4 in prolactin production by rat pituitary lactotrope GH3 cells.

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Ogura-Ochi, Kanako; Fujisawa, Satoshi; Iwata, Nahoko; Komatsubara, Motoshi; Nishiyama, Yuki; Tsukamoto-Yamauchi, Naoko; Inagaki, Kenichi; Wada, Jun; Otsuka, Fumio

2017-08-01

The effects of melatonin on prolactin production and its regulatory mechanism remain uncertain. We investigated the regulatory role of melatonin in prolactin production using rat pituitary lactotrope GH3 cells by focusing on the bone morphogenetic protein (BMP) system. Melatonin receptor activation, induced by melatonin and its receptor agonist ramelteon, significantly suppressed basal and forskolin-induced prolactin secretion and prolactin mRNA expression in GH3 cells. The melatonin MT2 receptor was predominantly expressed in GH3 cells, and the inhibitory effects of melatonin on prolactin production were reversed by treatment with the receptor antagonist luzindole, suggesting functional involvement of MT2 action in the suppression of prolactin release. Melatonin receptor activation also suppressed BMP-4-induced prolactin expression by inhibiting phosphorylation of Smad and transcription of the BMP-target gene Id-1, while BMP-4 treatment upregulated MT2 expression. Melatonin receptor activation suppressed basal, BMP-4-induced and forskolin-induced cAMP synthesis; however, BtcAMP-induced prolactin mRNA expression was not affected by melatonin or ramelteon, suggesting that MT2 activation leads to inhibition of prolactin production through the suppression of Smad signaling and cAMP synthesis. Experiments using intracellular signal inhibitors revealed that the ERK pathway is, at least in part, involved in prolactin induction by GH3 cells. Thus, a new regulatory role of melatonin involving BMP-4 in prolactin secretion was uncovered in lactotrope GH3 cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Regulation of the voltage-gated Ca2+ channel CaVα2δ-1 subunit expression by the transcription factor Egr-1.

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González-Ramírez, Ricardo; Martínez-Hernández, Elizabeth; Sandoval, Alejandro; Gómez-Mora, Kimberly; Felix, Ricardo

2018-04-23

It is well known that the Ca V α 2 δ auxiliary subunit regulates the density of high voltage-activated Ca 2+ channels in the plasma membrane and that alterations in their functional expression might have implications in the pathophysiology of diverse human diseases such as neuropathic pain. However, little is known concerning the transcriptional regulation of this protein. We previously characterized the promoter of Ca V α 2 δ, and here we report its regulation by the transcription factor Egr-1. Using the neuroblastoma N1E-115 cells, we found that Egr-1 interacts specifically with its binding site in the promoter, affecting the transcriptional regulation of Ca V α 2 δ. Overexpression and knockdown analysis of Egr-1 showed significant changes in the transcriptional activity of the Ca V α 2 δ promoter. Egr-1 also regulated the expression of Ca V α 2 δ at the level of protein. Also, functional studies showed that Egr-1 knockdown significantly decreases Ca 2+ currents in dorsal root ganglion (DRG) neurons, while overexpression of the transcription factor increased Ca 2+ currents in the F11 cell line, a hybrid of DRG and N18TG2 neuroblastoma cells. Studying the effects of Egr-1 on the transcriptional expression of Ca V α 2 δ could help to understand the regulatory mechanisms of this protein in both health and disease. Copyright © 2018 Elsevier B.V. All rights reserved.

The Immediate Early Gene Egr3 Is Required for Hippocampal Induction of Bdnf by Electroconvulsive Stimulation

Directory of Open Access Journals (Sweden)

Kimberly T. Meyers

2018-05-01

Full Text Available Early growth response 3 (Egr3 is an immediate early gene (IEG that is regulated downstream of a cascade of genes associated with risk for psychiatric disorders, and dysfunction of Egr3 itself has been implicated in schizophrenia, bipolar disorder, and depression. As an activity-dependent transcription factor, EGR3 is poised to regulate the neuronal expression of target genes in response to environmental events. In the current study, we sought to identify a downstream target of EGR3 with the goal of further elucidating genes in this biological pathway relevant for psychiatric illness risk. We used electroconvulsive stimulation (ECS to induce high-level expression of IEGs in the brain, and conducted expression microarray to identify genes differentially regulated in the hippocampus of Egr3-deficient (-/- mice compared to their wildtype (WT littermates. Our results replicated previous work showing that ECS induces high-level expression of the brain-derived neurotrophic factor (Bdnf in the hippocampus of WT mice. However, we found that this induction is absent in Egr3-/- mice. Quantitative real-time PCR (qRT-PCR validated the microarray results (performed in males and replicated the findings in two separate cohorts of female mice. Follow-up studies of activity-dependent Bdnf exons demonstrated that ECS-induced expression of both exons IV and VI requires Egr3. In situ hybridization demonstrated high-level cellular expression of Bdnf in the hippocampal dentate gyrus following ECS in WT, but not Egr3-/-, mice. Bdnf promoter analysis revealed eight putative EGR3 binding sites in the Bdnf promoter, suggesting a mechanism through which EGR3 may directly regulate Bdnf gene expression. These findings do not appear to result from a defect in the development of hippocampal neurons in Egr3-/- mice, as cell counts in tissue sections stained with anti-NeuN antibodies, a neuron-specific marker, did not differ between Egr3-/- and WT mice. In addition, Sholl

Effects of arachidonic acid and 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine on prolactin secretion from anterior pituitary cells

International Nuclear Information System (INIS)

Camoratto, A.M.

1988-01-01

The role of two lipids, arachidonic acid and 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine, as modulators or prolactin secretion has been examined. Stimulators of phospholipase A 2 activity, melittin and mastoparan, were found to increase prolactin release. Melittin also caused release of previously incorporated 3 H-arachidonic acid and this effect was associated with loss of radiolabel from the phospholipid fraction. Exogenous arachidonic acid also stimulated prolactin secretion. Conversely, inhibitors of phospholipase A 2 activity, dibromoacetophenone and U10029A, decreased basal and stimulated prolactin release. Prolactin release could also be lowered by ETYA, BW755C and NDGA, inhibitors of arachidonic acid metabolism. In the second series of experiments the effects of the biologically active phospholipid 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (platelet activating factor, PAF) on prolactin release were examined. PAF is an ether-linked phospholipid known to stimulate granule release in a variety of cell types including both inflammatory and noninflammatory cells. PAF increased release of prolactin from dispersed rat anterior pituitary cells; stimulation was not due to cell lysis. PAF-induced prolactin release could be blocked by the dopaminergic agonists apomorphine and bromocriptine as well as by two PAF receptor antagonists, SRI 63-072 and L-652-731

Hypomethylation of inflammatory genes (COX2, EGR1, and SOCS3) and increased urinary 8-nitroguanine in arsenic-exposed newborns and children

Energy Technology Data Exchange (ETDEWEB)

Phookphan, Preeyaphan; Navasumrit, Panida [Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Laksi, Bangkok (Thailand); Post-graduate Program in Environmental Toxicology, Chulabhorn Graduate Institute, Laksi, Bangkok (Thailand); Center of Excellence on Environmental Health, Toxicology (EHT), Office of the Higher Education Commission, Ministry of Education (Thailand); Waraprasit, Somchamai; Promvijit, Jeerawan; Chaisatra, Krittinee; Ngaotepprutaram, Thitirat [Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Laksi, Bangkok (Thailand); Ruchirawat, Mathuros, E-mail: mathuros@cri.or.th [Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Laksi, Bangkok (Thailand); Center of Excellence on Environmental Health, Toxicology (EHT), Office of the Higher Education Commission, Ministry of Education (Thailand)

2017-02-01

Early-life exposure to arsenic increases risk of developing a variety of non-malignant and malignant diseases. Arsenic-induced carcinogenesis may be mediated through epigenetic mechanisms and pathways leading to inflammation. Our previous study reported that prenatal arsenic exposure leads to increased mRNA expression of several genes related to inflammation, including COX2, EGR1, and SOCS3. This study aimed to investigate the effects of arsenic exposure on promoter DNA methylation and mRNA expression of these inflammatory genes (COX2, EGR1, and SOCS3), as well as the generation of 8-nitroguanine, which is a mutagenic DNA lesion involved in inflammation-related carcinogenesis. Prenatally arsenic-exposed newborns had promoter hypomethylation of COX2, EGR1, and SOCS3 in cord blood lymphocytes (p < 0.01). A follow-up study in these prenatally arsenic-exposed children showed a significant hypomethylation of these genes in salivary DNA (p < 0.01). In vitro experiments confirmed that arsenite treatment at short-term high doses (10–100 μM) and long-term low doses (0.5–1 μM) in human lymphoblasts (RPMI 1788) caused promoter hypomethylation of these genes, which was in concordance with an increase in their mRNA expression. Additionally, the level of urinary 8-nitroguanine was significantly higher (p < 0.01) in exposed newborns and children, by 1.4- and 1.8-fold, respectively. Arsenic accumulation in toenails was negatively correlated with hypomethylation of these genes and positively correlated with levels of 8-nitroguanine. These results indicated that early-life exposure to arsenic causes hypomethylation of COX2, EGR1, and SOCS3, increases mRNA expression of these genes, and increases 8-nitroguanine formation. These effects may be linked to mechanisms of arsenic-induced inflammation and cancer development later in life. - Highlight: • Early-life arsenic exposure caused promoter hypomethylation of COX2, EGR1 and SOCS3. • Hypomethylation of these genes is

Hypomethylation of inflammatory genes (COX2, EGR1, and SOCS3) and increased urinary 8-nitroguanine in arsenic-exposed newborns and children

International Nuclear Information System (INIS)

Phookphan, Preeyaphan; Navasumrit, Panida; Waraprasit, Somchamai; Promvijit, Jeerawan; Chaisatra, Krittinee; Ngaotepprutaram, Thitirat; Ruchirawat, Mathuros

2017-01-01

Early-life exposure to arsenic increases risk of developing a variety of non-malignant and malignant diseases. Arsenic-induced carcinogenesis may be mediated through epigenetic mechanisms and pathways leading to inflammation. Our previous study reported that prenatal arsenic exposure leads to increased mRNA expression of several genes related to inflammation, including COX2, EGR1, and SOCS3. This study aimed to investigate the effects of arsenic exposure on promoter DNA methylation and mRNA expression of these inflammatory genes (COX2, EGR1, and SOCS3), as well as the generation of 8-nitroguanine, which is a mutagenic DNA lesion involved in inflammation-related carcinogenesis. Prenatally arsenic-exposed newborns had promoter hypomethylation of COX2, EGR1, and SOCS3 in cord blood lymphocytes (p < 0.01). A follow-up study in these prenatally arsenic-exposed children showed a significant hypomethylation of these genes in salivary DNA (p < 0.01). In vitro experiments confirmed that arsenite treatment at short-term high doses (10–100 μM) and long-term low doses (0.5–1 μM) in human lymphoblasts (RPMI 1788) caused promoter hypomethylation of these genes, which was in concordance with an increase in their mRNA expression. Additionally, the level of urinary 8-nitroguanine was significantly higher (p < 0.01) in exposed newborns and children, by 1.4- and 1.8-fold, respectively. Arsenic accumulation in toenails was negatively correlated with hypomethylation of these genes and positively correlated with levels of 8-nitroguanine. These results indicated that early-life exposure to arsenic causes hypomethylation of COX2, EGR1, and SOCS3, increases mRNA expression of these genes, and increases 8-nitroguanine formation. These effects may be linked to mechanisms of arsenic-induced inflammation and cancer development later in life. - Highlight: • Early-life arsenic exposure caused promoter hypomethylation of COX2, EGR1 and SOCS3. • Hypomethylation of these genes is

Zif268/Egr1 gain of function facilitates hippocampal synaptic plasticity and long-term spatial recognition memory.

Science.gov (United States)

Penke, Zsuzsa; Morice, Elise; Veyrac, Alexandra; Gros, Alexandra; Chagneau, Carine; LeBlanc, Pascale; Samson, Nathalie; Baumgärtel, Karsten; Mansuy, Isabelle M; Davis, Sabrina; Laroche, Serge

2014-01-05

It is well established that Zif268/Egr1, a member of the Egr family of transcription factors, is critical for the consolidation of several forms of memory; however, it is as yet uncertain whether increasing expression of Zif268 in neurons can facilitate memory formation. Here, we used an inducible transgenic mouse model to specifically induce Zif268 overexpression in forebrain neurons and examined the effect on recognition memory and hippocampal synaptic transmission and plasticity. We found that Zif268 overexpression during the establishment of memory for objects did not change the ability to form a long-term memory of objects, but enhanced the capacity to form a long-term memory of the spatial location of objects. This enhancement was paralleled by increased long-term potentiation in the dentate gyrus of the hippocampus and by increased activity-dependent expression of Zif268 and selected Zif268 target genes. These results provide novel evidence that transcriptional mechanisms engaging Zif268 contribute to determining the strength of newly encoded memories.

High frequency of tumor cells with nuclear Egr-1 protein expression in human bladder cancer is associated with disease progression

DEFF Research Database (Denmark)

Egerod, Frederikke N S Lihme; Bartels, Annette; Fristrup, Niels

2009-01-01

bladder cancer. RESULTS: The frequency of tumor cells with nuclear Egr-1 immunolabelling correlated to bladder cancer stage, grade and to later progression to muscle-invasive bladder cancer (T2-4). Stage T1 tumors exhibited significantly higher frequencies of tumor cells with nuclear Egr-1 immunolabelling...... than Ta tumors (P = 0.001). Furthermore, Kaplan-Meier survival analysis showed that a high frequency of tumor cells with nuclear Egr-1 immunolabelling was significantly associated with a higher risk of progression to stage T2-4 (log-rank test, P = 0.035). Tumor cells with nuclear Egr-1 immunolabelling...

Prolactin release, oestrogens and proliferation of prolactin-secreting cells in the anterior pituitary gland of adult male rats.

Science.gov (United States)

Pérez, R L; Machiavelli, G A; Romano, M I; Burdman, J A

1986-03-01

Relationships among the release of prolactin, the effect of oestrogens and the proliferation of prolactin-secreting cells were studied under several experimental conditions. Administration of sulpiride or oestradiol released prolactin and stimulated cell proliferation in the anterior pituitary gland of adult male rats. Clomiphene completely abolished the rise in cell proliferation, but did not interfere with the sulpiride-induced release of prolactin. Treatment with oestradiol plus sulpiride significantly increased serum prolactin concentrations and the mitotic index compared with the sum of the stimulation produced by both drugs separately. Bromocriptine abolished the stimulatory effect of oestradiol on the serum prolactin concentration and on cell proliferation. In oestradiol- and/or sulpiride-treated rats, 80% of the cells in mitoses were lactotrophs. The remaining 20% did not stain with antisera against any of the pituitary hormones. The number of prolactin-secreting cells in the anterior pituitary gland significantly increased after the administration of oestradiol or sulpiride. The results demonstrate that treatment with sulpiride and/or oestradiol increases the proliferation and the number of lactotrophs in the anterior pituitary gland of the rat.

Paradoxical effects of oxytocin and vasopressin on basal prolactin secretion and the estrogen-induced prolactin surge

International Nuclear Information System (INIS)

Mai, Leemin; Pan, Jenntser

1990-01-01

The roles of oxytocin (OT) and vasopressin (AVP) on both basal and estrogen-induced prolactin (PRL) secretion were examined. Adult female Sprague-Dawley rats that were ovariectomized for 3 weeks and received estrogen treatment for 1 week were used. Intravenous administration of hormones and serial blood sampling were accomplished through indwelling intraatrial catheters which were implanted two days before. Plasma PRL levels were measured by radioimmunoassay. Oxytocin at a dose of 20 μg/rat stimulated a moderate PRL release in the morning and lower doses were without effect. Vasopressin was most effective at a dose of 5 μg/rat in stimulating PRL release, while consecutive injections of higher doses were less effective. In contrast, TRH, ranging from 1 to 8 μg/rat, induced a dose-dependent increases in PRL secretion. Using the effective dosages determined from the morning studies, repeated injections of either OT, AVP or their specific antagonists MPOMeOVT were given hourly between 1300 to 1800h and blood samples were obtained hourly from 1100 to 1900h. It was found that either OT or AVP significantly reduced the afternoon PRL surge, while their antagonists were not as effective

Amitriptyline induces early growth response-1 gene expression via ERK and JNK mitogen-activated protein kinase pathways in rat C6 glial cells.

Science.gov (United States)

Chung, Eun Young; Shin, Soon Young; Lee, Young Han

2007-07-05

Astrocytes play important roles in guiding the construction of the nervous system, controlling extracellular ions and neurotransmitters, and regulating CNS synaptogenesis. Egr-1 is a transcription factor involved in neuronal differentiation and astrocyte cell proliferation. In this study, we investigated whether the tricyclic antidepressant (TCA) amitriptyline induces Egr-1 expression in astrocytes using rat C6 glioma cells as a model. We found that amitriptyline increased the expression of Egr-1 in a dose- and time-dependent manner. The amitriptyline-induced Egr-1 expression was mediated through serum response elements (SREs) in the Egr-1 promoter. SREs were activated by the Ets-domain transcription factor Elk-1 through the ERK and JNK mitogen-activated protein (MAP) kinase pathways. The inhibition of the ERK and JNK MAP kinase signals attenuated amitriptyline-induced transactivation of Gal4-Elk-1 and Egr-1 promoter activity. Our findings suggest that the induction of Egr-1 expression in astrocytes may be required to attain the therapeutic effects of antidepressant drugs.

The constitutive activation of Egr-1/C/EBPa mediates the development of type 2 diabetes mellitus by enhancing hepatic gluconeogenesis.

Science.gov (United States)

Shen, Ning; Jiang, Shan; Lu, Jia-Ming; Yu, Xiao; Lai, Shan-Shan; Zhang, Jing-Zi; Zhang, Jin-Long; Tao, Wei-Wei; Wang, Xiu-Xing; Xu, Na; Xue, Bin; Li, Chao-Jun

2015-02-01

The sequential secretion of insulin and glucagon delicately maintains glucose homeostasis by inhibiting or enhancing hepatic gluconeogenesis during postprandial or fasting states, respectively. Increased glucagon/insulin ratio is believed to be a major cause of the hyperglycemia seen in type 2 diabetes. Herein, we reveal that the early growth response gene-1 (Egr-1) can be transiently activated by glucagon in hepatocytes, which mediates glucagon-regulated gluconeogenesis by increasing the expression of gluconeogenesis genes. Blockage of Egr-1 function in the liver of mice led to lower fasting blood glucose, better pyruvate tolerance, and higher hepatic glycogen content. The mechanism analysis demonstrated that Egr-1 can directly bind to the promoter of C/EBPa and regulate the expression of gluconeogenesis genes in the later phase of glucagon stimulation. The transient increase of Egr-1 by glucagon kept the glucose homeostasis after fasting for longer periods of time, whereas constitutive Egr-1 elevation found in the liver of db/db mice and high serum glucagon level overactivated the C/EBPa/gluconeogenesis pathway and resulted in hyperglycemia. Blockage of Egr-1 activation in prediabetic db/db mice was able to delay the progression of diabetes. Our results suggest that dysregulation of Egr-1/C/EBPa on glucagon stimulation may provide an alternative mechanistic explanation for type 2 diabetes. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Androgen Modulates Functions of Endothelial Progenitor Cells through Activated Egr1 Signaling

Directory of Open Access Journals (Sweden)

Yizhou Ye

2016-01-01

Full Text Available Researches show that androgens have important effects on migration of endothelial cells and endothelial protection in coronary heart disease. Endothelial progenitor cells (EPCs as a progenitor cell type that can differentiate into endothelial cells, have a critical role in angiogenesis and endothelial protection. The relationship between androgen and the functions of EPCs has animated much interest and controversy. In this study, we investigated the angiogenic and migratory functions of EPCs after treatment by dihydrotestosterone (DHT and the molecular mechanisms as well. We found that DHT treatment enhanced the incorporation of EPCs into tubular structures formed by HUVECs and the migratory activity of EPCs in the transwell assay dose dependently. Moreover, microarray analysis was performed to explore how DHT changes the gene expression profiles of EPCs. We found 346 differentially expressed genes in androgen-treated EPCs. Angiogenesis-related genes like Egr-1, Vcan, Efnb2, and Cdk2ap1 were identified to be regulated upon DHT treatment. Furthermore, the enhanced angiogenic and migratory abilities of EPCs after DHT treatment were inhibited by Egr1-siRNA transfection. In conclusion, our findings suggest that DHT markedly enhances the vessel forming ability and migration capacity of EPCs. Egr1 signaling may be a possible pathway in this process.

Attenuation of pCREB and Egr1 expression in the insular and anterior cingulate cortices associated with enhancement of CFA-evoked mechanical hypersensitivity after repeated forced swim stress.

Science.gov (United States)

Imbe, Hiroki; Kimura, Akihisa

2017-09-01

The perception and response to pain are severely impacted by exposure to stressors. In some animal models, stress increases pain sensitivity, which is termed stress-induced hyperalgesia (SIH). The insular cortex (IC) and anterior cingulate cortex (ACC), which are typically activated by noxious stimuli, affect pain perception through the descending pain modulatory system. In the present study, we examined the expression of phospho-cAMP response element-binding protein (pCREB) and early growth response 1 (Egr1) in the IC and ACC at 3h (the acute phase of peripheral tissue inflammation) after complete Freund's adjuvant (CFA) injection in naïve rats and rats preconditioned with forced swim stress (FS) to clarify the effect of FS, a stressor, on cortical cell activities in the rats showing SIH induced by FS. The CFA injection into the hindpaw induced mechanical hypersensitivity and increased the expression of the pCREB and Egr1 in the IC and ACC at 3h after the injection. FS (day 1, 10min; days 2-3, 20min) prior to the CFA injection enhanced the CFA-induced mechanical hypersensitivity and attenuated the increase in the expression of pCREB and Egr1 in the IC and ACC. These findings suggested that FS modulates the CFA injection-induced neuroplasticity in the IC and ACC to enhance the mechanical hypersensitivity. These findings are thought to signify stressor-induced dysfunction of the descending pain modulatory system. Copyright © 2017 Elsevier Inc. All rights reserved.

Prostate response to prolactin in sexually active male rats

Directory of Open Access Journals (Sweden)

Garcia Luis I

2006-05-01

Full Text Available Abstract Background The prostate is a key gland in the sexual physiology of male mammals. Its sensitivity to steroid hormones is widely known, but its response to prolactin is still poorly known. Previous studies have shown a correlation between sexual behaviour, prolactin release and prostate physiology. Thus, here we used the sexual behaviour of male rats as a model for studying this correlation. Hence, we developed experimental paradigms to determine the influence of prolactin on sexual behaviour and prostate organization of male rats. Methods In addition to sexual behaviour recordings, we developed the ELISA procedure to quantify the serum level of prolactin, and the hematoxilin-eosin technique for analysis of the histological organization of the prostate. Also, different experimental manipulations were carried out; they included pituitary grafts, and haloperidol and ovine prolactin treatments. Data were analyzed with a One way ANOVA followed by post hoc Dunnet test if required. Results Data showed that male prolactin has a basal level with two peaks at the light-dark-light transitions. Consecutive ejaculations increased serum prolactin after the first ejaculation, which reached the highest level after the second, and started to decrease after the third ejaculation. These normal levels of prolactin did not induce any change at the prostate tissue. However, treatments for constant elevations of serum prolactin decreased sexual potency and increased the weight of the gland, the alveoli area and the epithelial cell height. Treatments for transient elevation of serum prolactin did not affect the sexual behaviour of males, but triggered these significant effects mainly at the ventral prostate. Conclusion The prostate is a sexual gland that responds to prolactin. Mating-induced prolactin release is required during sexual encounters to activate the epithelial cells in the gland. Here we saw a precise mechanism controlling the release of prolactin

Tet1 overexpression leads to anxiety-like behavior and enhanced fear memories via the activation of calcium-dependent cascade through Egr1 expression in mice.

Science.gov (United States)

Kwon, Wookbong; Kim, Hyeng-Soo; Jeong, Jain; Sung, Yonghun; Choi, Minjee; Park, Song; Lee, Jinhee; Jang, Soyoung; Kim, Sung Hyun; Lee, Sanggyu; Kim, Myoung Ok; Ryoo, Zae Young

2018-01-01

Ten-eleven translocation methylcytosine dioxygenase 1 ( Tet1 ) initiates DNA demethylation by converting 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) at CpG-rich regions of genes, which have key roles in adult neurogenesis and memory. In addition, the overexpression of Tet1 with 5-hmC alteration in patients with psychosis has also been reported, for instance in schizophrenia and bipolar disorders. The mechanism underlying Tet1 overexpression in the brain; however, is still elusive. In the present study, we found that Tet1-transgenic (Tet1-TG) mice displayed abnormal behaviors involving elevated anxiety and enhanced fear memories. We confirmed that Tet1 overexpression affected adult neurogenesis with oligodendrocyte differentiation in the hippocampal dentate gyrus of Tet1-TG mice. In addition, Tet1 overexpression induced the elevated expression of immediate early genes, such as Egr1 , c-fos , Arc , and Bdnf , followed by the activation of intracellular calcium signals ( i.e. , CamKII, ERK, and CREB) in prefrontal and hippocampal neurons. The expression of GABA receptor subunits ( Gabra2 and Gabra4 ) fluctuated in the prefrontal cortex and hippocampus. We evaluated the effects of Tet1 overexpression on intracellular calcium-dependent cascades by activating the Egr1 promoter in vitro Tet1 enhanced Egr1 expression, which may have led to alterations in Gabra2 and Gabra4 expression in neurons. Taken together, we suggest that the Tet1 overexpression in our Tet1-TG mice can be applied as an effective model for studying various stress-related diseases that show hyperactivation of intracellular calcium-dependent cascades in the brain.-Kwon, W., Kim, H.-S., Jeong, J., Sung, Y., Choi, M., Park, S., Lee, J., Jang, S., Kim, S. H., Lee, S., Kim, M. O., Ryoo, Z. Y. Tet1 overexpression leads to anxiety-like behavior and enhanced fear memories via the activation of calcium-dependent cascade through Egr1 expression in mice. © FASEB.

Long-term recognition memory of individual conspecifics is associated with telencephalic expression of Egr-1 in the electric fish Apteronotus leptorhynchus.

Science.gov (United States)

Harvey-Girard, Erik; Tweedle, Jessica; Ironstone, Joel; Cuddy, Martin; Ellis, William; Maler, Leonard

2010-07-15

Primates and songbirds can learn to recognize individual conspecifics based on complex sensory cues; this requires a large, highly differentiated dorsal telencephalon. Here we show that the electric fish Apteronotus leptorhynchus can learn to recognize individual conspecifics based on a simple cue, the beat frequency of their summed sinusoidal electric organ discharges (EOD). Male fish produce transient communication signals (chirps) in response to mimic EODs. The chirp response habituates over repeated stimulus presentations within one experimental session, continues to habituate over successive daily sessions and is nearly extinguished after 5-7 days. Habituation of the chirp response was specific to the presented beat frequency. The conversion of short- to long-term habituation could be disrupted by cooling the head 30 minutes after the daily habituation trials. Consolidation of long-term memory in mammals is thought to involve induced expression of an immediate early gene, Egr-1. We cloned the Apteronotid homolog of the Egr-1 gene and found that chirp-evoking stimuli induced strong expression of its mRNA within the dorsal (Dd), central (DC), and lateral (DL) subdivisions of the dorsal telencephalon. Interestingly, the dorsolateral region is hypothesized to be homologous to the amniote hippocampal formation. We conclude that A. leptorhynchus can learn to identify individual conspecifics based on their EOD frequency and can remember these frequencies for several days. We hypothesize that this form of learning, as in primates and songbirds, requires a subset of dorsal telencephalic areas and involves a consolidation-like process that includes the expression of the transcription factor AptEgr-1.

Appliance of high EGR rates with a short and long route EGR system on a heavy duty diesel engine

NARCIS (Netherlands)

Aken, van M.; Willems, F.P.T.; Jong, de D.J.

2007-01-01

The goal of this work was to investigate the possibilities of applying high EGR rates with low NOx and PM emission levels on a two-stage turbocharged 12 liter heavy duty diesel engine. The EGR is applied by using a long and short route EGR system. For the ESC operating points A25 and C100 EGR is

PAK1 translocates into nucleus in response to prolactin but not to estrogen

Energy Technology Data Exchange (ETDEWEB)

Oladimeji, Peter, E-mail: Peter.Oladimeji@rockets.utoledo.edu; Diakonova, Maria, E-mail: mdiakon@utnet.utoledo.edu

2016-04-22

Tyrosyl phosphorylation of the p21-activated serine–threonine kinase 1 (PAK1) has an essential role in regulating PAK1 functions in breast cancer cells. We previously demonstrated that PAK1 serves as a common node for estrogen (E2)- and prolactin (PRL)-dependent pathways. We hypothesize herein that intracellular localization of PAK1 is affected by PRL and E2 treatments differently. We demonstrate by immunocytochemical analysis that PAK1 nuclear translocation is ligand-dependent: only PRL but not E2 stimulated PAK1 nuclear translocation. Tyrosyl phosphorylation of PAK1 is essential for this nuclear translocation because phospho-tyrosyl-deficient PAK1 Y3F mutant is retained in the cytoplasm in response to PRL. We confirmed these data by Western blot analysis of subcellular fractions. In 30 min of PRL treatment, only 48% of pTyr-PAK1 is retained in the cytoplasm of PAK1 WT clone while 52% re-distributes into the nucleus and pTyr-PAK1 shuttles back to the cytoplasm by 60 min of PRL treatment. In contrast, PAK1 Y3F is retained in the cytoplasm. E2 treatment causes nuclear translocation of neither PAK1 WT nor PAK1 Y3F. Finally, we show by an in vitro kinase assay that PRL but not E2 stimulates PAK1 kinase activity in the nuclear fraction. Thus, PAK1 nuclear translocation is ligand-dependent: PRL activates PAK1 and induces translocation of activated pTyr-PAK1 into nucleus while E2 activates pTyr-PAK1 only in the cytoplasm. - Highlights: • Prolactin but not estrogen causes translocation of PAK1 into nucleus. • Tyrosyl phosphorylation of PAK1 is required for nuclear localization. • Prolactin but not estrogen stimulates PAK1 kinase activity in nucleus.

Prolactins, ch. 11

International Nuclear Information System (INIS)

Friesen, H.; Guyda, H.; Hwang, P.

1976-01-01

A radioimmunoassay for primate prolactin is described. Synthesis, secretion and immunological properties of prolactin in comparison to the human growth hormone and separation of the two are studied using 3 H-L-leucine. Prolactin was labelled with 131 I by the chloramine-T method of Hunter and Greenwood. Purification was performed by a sepharose column, coupled with antibodies to ovine prolactine from which the prolactin is subsequently eluted. The assay procedure and the cross-reactivity of different materials in the assay are described. Prolactin concentrations in healthy people, patients and pregnant women (amniotic fluid) are examined

Egr-1 antisense oligodeoxynucleotide administration into the olfactory bulb impairs olfactory learning in the greater short-nosed fruit bat Cynopterus sphinx.

Science.gov (United States)

Ganesh, Ambigapathy; Bogdanowicz, Wieslaw; Balamurugan, Krishnaswamy; Ragu Varman, Durairaj; Rajan, Koilmani Emmanuvel

2012-08-30

Postsynaptic densities (PSDs) contain proteins that regulate synaptic transmission. We examined two important examples of these, calcium/calmodulin-dependent protein kinase II (CaMKII) and PSD-95, in regard to the functional role of early growth response gene-1 (egr-1) in regulation of olfactory learning in the greater short-nosed fruit bat Cynopterus sphinx (family Pteropodidae). To test whether activation of egr-1 in the olfactory bulb (OB) is required for olfactory memory of these bats, bilaterally canulated individuals were infused with antisense (AS) or non-sense (NS)-oligodeoxynucleotides (ODN) of egr-1, or with phosphate buffer saline (PBS), 2h before the olfactory training. Our results showed that behavioral training significantly up-regulates immediate early gene (IEG) EGR-1 and key synaptic proteins Synaptotagmin-1(SYT-1), CaMKII and PSD-95, and phosphorylation of CaMKII in the OB at the protein level per se. Subsequently, we observed that egr-1 antisense-ODN infusion in the OB impaired olfactory memory and down regulates the expression of CaMKII and PSD-95, and the phosphorylation of CaMKII but not SYT-1. In contrast, NS-ODN or PBS had no effect on the expression of the PSDs CaMKII or PSD-95, or on the phosphorylation of CaMKII. When the egr-1 NS-ODN was infused in the OB after training for the novel odor there was no effect on olfactory memory. These findings suggest that egr-1 control the activation of CaMKII and PSD-95 during the process of olfactory memory formation. Copyright © 2012 Elsevier B.V. All rights reserved.

20(S)-protopanaxadiol (PPD) alleviates scopolamine-induced memory impairment via regulation of cholinergic and antioxidant systems, and expression of Egr-1, c-Fos and c-Jun in mice.

Science.gov (United States)

Lu, Cong; Dong, Liming; Lv, Jingwei; Wang, Yan; Fan, Bei; Wang, Fengzhong; Liu, Xinmin

2018-01-05

20(S)-protopanaxadiol (PPD) possesses various biological properties, including anti-inflammatory, antitumor and anti-fatigue properties. Recent studies found that PPD functioned as a neurotrophic agent to ameliorate the sensory deficit caused by glutamate-induced excitotoxicity through its antioxidant effects and exhibited strong antidepressant-like effects in vivo. The objective of the present study was first to investigate the effect of PPD in scopolamine (SCOP)-induced memory deficit in mice and the potential mechanisms involved. In this study, mice were pretreated with PPD (20 and 40 μmol/kg) and donepezil (1.6 mg/kg) intraperitoneally (i.p) for 14 days. Then, open field test was used to assess the effect of PPD on the locomotor activity and mice were daily injected with SCOP (0.75 mg/kg) to induce cognitive deficits and then subjected to behavioral tests by object location recognition (OLR) experiment and Morris water maze (MWM) task. The cholinergic system function, oxidative stress biomarkers and protein expression of Egr-1, c-Fos, and c-Jun in mouse hippocampus were examined. PPD was found to significantly improve the performance of amnesia mice in OLR and MWM tests. PPD regulated cholinergic function by inhibiting SCOP-induced elevation of acetylcholinesterase (AChE) activity, decline of choline acetyltransferase (ChAT) activity and decrease of acetylcholine (Ach) level. PPD suppressed oxidative stress by increasing activities of antioxidant enzymes such as superoxide dismutase (SOD) and lowering maleic diadehyde (MDA) level. Additionally, PPD significantly elevated the expression of Egr-1, c-Fos, and c-Jun in hippocampus at protein level. Taken together, all these results suggested that 20(S)-protopanaxadiol (PPD) may be a candidate compound for the prevention against memory loss in some neurodegenerative diseases such as Alzheimer's disease (AD). Copyright © 2017. Published by Elsevier B.V.

Activation of PKCβII and PKCθ is essential for LDL-induced cell proliferation of human aortic smooth muscle cells via Gi-mediated Erk1/2 activation and Egr-1 upregulation

International Nuclear Information System (INIS)

Heo, Kyung-Sun; Kim, Dong-Uk; Kim, Lila; Nam, Miyoung; Baek, Seung-Tae; Park, Song-Kyu; Park, Youngwoo; Myung, Chang-Seon; Hwang, Sung-Ook; Hoe, Kwang-Lae

2008-01-01

Native LDL may be a mitogenic stimulus of VSMC proliferation in lesions where endothelial disruption occurs. Recent studies have demonstrated that the mitogenic effects of LDL are accompanied by Erk1/2 activation via an unknown G-protein-coupled receptor (GPCR). In this article, we report that LDL translocated PKCβ II and PKCθ from cytosol to plasma membrane, and inhibition of PKCβ II and PKCθ decreased LDL effects via the deactivation of Erk1/2. Moreover, pertussis toxin, but not cholera toxin or heparin, inhibited LDL-induced translocation of PKCβ II and PKCθ, suggesting that Gi protein plays a role in LDL effects. Of LPA, S1P, and LDL, whose signaling is conveyed via Gi/o proteins, only LDL induced translocation of PKCβ II and PKCθ. Inhibition of PKCβ II or PKCθ, as well as of Erk1/2 and GPCR, decreases LDL-induced upregulation of Egr-1, which is critical for cell proliferation. This is the first report, to our knowledge, that the participation of PKCθ in VSMC proliferation is unique

Prolactin induces apoptosis of lactotropes in female rodents.

Directory of Open Access Journals (Sweden)

Jimena Ferraris

Full Text Available Anterior pituitary cell turnover occurring during female sexual cycle is a poorly understood process that involves complex regulation of cell proliferation and apoptosis by multiple hormones. In rats, the prolactin (PRL surge that occurs at proestrus coincides with the highest apoptotic rate. Since anterior pituitary cells express the prolactin receptor (PRLR, we aimed to address the actual role of PRL in the regulation of pituitary cell turnover in cycling females. We showed that acute hyperprolactinemia induced in ovariectomized rats using PRL injection or dopamine antagonist treatment rapidly increased apoptosis and decreased proliferation specifically of PRL producing cells (lactotropes, suggesting a direct regulation of these cell responses by PRL. To demonstrate that apoptosis naturally occurring at proestrus was regulated by transient elevation of endogenous PRL levels, we used PRLR-deficient female mice (PRLRKO in which PRL signaling is totally abolished. According to our hypothesis, no increase in lactotrope apoptotic rate was observed at proestrus, which likely contributes to pituitary tumorigenesis observed in these animals. To decipher the molecular mechanisms underlying PRL effects, we explored the isoform-specific pattern of PRLR expression in cycling wild type females. This analysis revealed dramatic changes of long versus short PRLR ratio during the estrous cycle, which is particularly relevant since these isoforms exhibit distinct signaling properties. This pattern was markedly altered in a model of chronic PRLR signaling blockade involving transgenic mice expressing a pure PRLR antagonist (TGΔ1-9-G129R-hPRL, providing evidence that PRL regulates the expression of its own receptor in an isoform-specific manner. Taken together, these results demonstrate that i the PRL surge occurring during proestrus is a major proapoptotic signal for lactotropes, and ii partial or total deficiencies in PRLR signaling in the anterior pituitary

HTLV-1 Tax upregulates early growth response protein 1 through nuclear factor-κB signaling.

Science.gov (United States)

Huang, Qingsong; Niu, Zhiguo; Han, Jingxian; Liu, Xihong; Lv, Zhuangwei; Li, Huanhuan; Yuan, Lixiang; Li, Xiangping; Sun, Shuming; Wang, Hui; Huang, Xinxiang

2017-08-01

Human T cell leukemia virus type 1 (HTLV-1) is a complex retrovirus that causes adult T cell leukemia (ATL) in susceptible individuals. The HTLV-1-encoded oncoprotein Tax induces persistent activation of the nuclear factor-κB (NF-κB) pathway. Early growth response protein 1 (EGR1) is overexpressed in HTLV-1-infected T cell lines and ATL cells. Here, we showed that both Tax expression and HTLV-1 infection promoted EGR1 overexpression. Loss of the NF-κB binding site in the EGR1 promotor or inhibition of NF-κB activation reduced Tax-induced EGR1 upregulation. Tax mutants unable to activate NF-κB induced only slight EGR1 upregulation as compared with wild-type Tax, confirming NF-κB pathway involvement in EGR1 regulation. Tax also directly interacted with the EGR1 protein and increased endogenous EGR1 stability. Elevated EGR1 in turn promoted p65 nuclear translocation and increased NF-κB activation. These results demonstrate a positive feedback loop between EGR1 expression and NF-κB activation in HTLV-1-infected and Tax-expressing cells. Both NF-κB activation and Tax-induced EGR1 stability upregulated EGR1, which in turn enhanced constitutive NF-κB activation and facilitated ATL progression in HTLV-1-infected cells. These findings suggest EGR1 may be an effective anti-ATL therapeutic target.

EGR-1 and DUSP-1 are important negative regulators of pro-allergic responses in airway epithelium

NARCIS (Netherlands)

Golebski, Korneliusz; van Egmond, Danielle; de Groot, Esther J.; Roschmann, Kristina I. L.; Fokkens, Wytske J.; van Drunen, Cornelis M.

2015-01-01

Background: Primary nasal epithelium of house dust mite allergic individuals is in a permanently activated inflammatory transcriptional state. Objective: To investigate whether a deregulated expression of EGR-1 and/or DUSP-1, two potential negative regulators of pro-inflammatory responses, could

EGR3 Immediate Early Gene and the Brain-Derived Neurotrophic Factor in Bipolar Disorder

Directory of Open Access Journals (Sweden)

Bianca Pfaffenseller

2018-02-01

Full Text Available Bipolar disorder (BD is a severe psychiatric illness with a consistent genetic influence, involving complex interactions between numerous genes and environmental factors. Immediate early genes (IEGs are activated in the brain in response to environmental stimuli, such as stress. The potential to translate environmental stimuli into long-term changes in brain has led to increased interest in a potential role for these genes influencing risk for psychiatric disorders. Our recent finding using network-based approach has shown that the regulatory unit of early growth response gene 3 (EGR3 of IEGs family was robustly repressed in postmortem prefrontal cortex of BD patients. As a central transcription factor, EGR3 regulates an array of target genes that mediate critical neurobiological processes such as synaptic plasticity, memory and cognition. Considering that EGR3 expression is induced by brain-derived neurotrophic factor (BDNF that has been consistently related to BD pathophysiology, we suggest a link between BDNF and EGR3 and their potential role in BD. A growing body of data from our group and others has shown that peripheral BDNF levels are reduced during mood episodes and also with illness progression. In this same vein, BDNF has been proposed as an important growth factor in the impaired cellular resilience related to BD. Taken together with the fact that EGR3 regulates the expression of the neurotrophin receptor p75NTR and may also indirectly induce BDNF expression, here we propose a feed-forward gene regulatory network involving EGR3 and BDNF and its potential role in BD.

Resveratrol-induced transcriptional up-regulation of ASMase (SMPD1) of human leukemia and cancer cells

Energy Technology Data Exchange (ETDEWEB)

Mizutani, Naoki [Department of Pathophysiological Laboratory Science, Nagoya University Graduate School of Medicine, Nagoya (Japan); College of Life and Health Sciences, Chubu University, Kasugai (Japan); Omori, Yukari [Department of Pathophysiological Laboratory Science, Nagoya University Graduate School of Medicine, Nagoya (Japan); Kawamoto, Yoshiyuki; Sobue, Sayaka; Ichihara, Masatoshi [College of Life and Health Sciences, Chubu University, Kasugai (Japan); Suzuki, Motoshi [Division of Molecular Carcinogenesis, Nagoya University Graduate School of Medicine, Nagoya (Japan); Kyogashima, Mamoru [Department of Microbiology and Molecular Biology, Nihon Pharmaceutical University, Saitama (Japan); Nakamura, Mitsuhiro [Department of Drug Information, Gifu Pharmaceutical University, Gifu (Japan); Tamiya-Koizumi, Keiko [College of Life and Health Sciences, Chubu University, Kasugai (Japan); Nozawa, Yoshinori [Tokai Gakuin University, Kakamigahara (Japan); Murate, Takashi, E-mail: murate@isc.chubu.ac.jp [College of Life and Health Sciences, Chubu University, Kasugai (Japan)

2016-02-19

Resveratrol (RSV) is a plant-derived phytoalexin present in plants, whose pleiotropic effects for health benefits have been previously reported. Its anti-cancer activity is among the current topics for novel cancer treatment. Here, effects of RSV on cell proliferation and the sphingolipid metabolism of K562, a human leukemia cell line, were analyzed. Some experiments were also performed in HCT116, a human colon cancer cell line. RSV inhibited cell proliferation of both cell lines. Increased cellular ceramide and decreased sphingomyelin and S1P by RSV were observed in RSV-treated K562 cells. Further analysis revealed that acid sphingomyelinase mRNA and enzyme activity levels were increased by RSV. Desipramine, a functional ASMase inhibitor, prevented RSV-induced ceramide increase. RSV increased ATF3, EGR1, EGR3 proteins and phosphorylated c-Jun and FOXO3. However, co-transfection using these transcription factor expression vectors and ASMase promoter reporter vector revealed positive effects of EGR1 and EGR3 but not others. Electrophoresis mobility shift assay (EMSA) and Chromatin immunoprecipitation (ChIP) assay demonstrated the direct binding of EGR1/3 transcription factors with ASMase 5′-promoter. These results indicate that increased EGR1/3 and ASMase expression play an important role in cellular ceramide increase by RSV treatment. - Highlights: • Resveratrol inhibited cell proliferation of K562 and HCT116 cells. • Resveratrol increased cellular ceramide and decreased sphingomyelin and S1P. • ASMase mRNA and activity were increased with resveratrol. • ASMase inhibition suppressed RSV-induced ceramide accumulation. • Increased ASMase transcription was at least partially due to EGR family proteins.

Resveratrol-induced transcriptional up-regulation of ASMase (SMPD1) of human leukemia and cancer cells

International Nuclear Information System (INIS)

Mizutani, Naoki; Omori, Yukari; Kawamoto, Yoshiyuki; Sobue, Sayaka; Ichihara, Masatoshi; Suzuki, Motoshi; Kyogashima, Mamoru; Nakamura, Mitsuhiro; Tamiya-Koizumi, Keiko; Nozawa, Yoshinori; Murate, Takashi

2016-01-01

Resveratrol (RSV) is a plant-derived phytoalexin present in plants, whose pleiotropic effects for health benefits have been previously reported. Its anti-cancer activity is among the current topics for novel cancer treatment. Here, effects of RSV on cell proliferation and the sphingolipid metabolism of K562, a human leukemia cell line, were analyzed. Some experiments were also performed in HCT116, a human colon cancer cell line. RSV inhibited cell proliferation of both cell lines. Increased cellular ceramide and decreased sphingomyelin and S1P by RSV were observed in RSV-treated K562 cells. Further analysis revealed that acid sphingomyelinase mRNA and enzyme activity levels were increased by RSV. Desipramine, a functional ASMase inhibitor, prevented RSV-induced ceramide increase. RSV increased ATF3, EGR1, EGR3 proteins and phosphorylated c-Jun and FOXO3. However, co-transfection using these transcription factor expression vectors and ASMase promoter reporter vector revealed positive effects of EGR1 and EGR3 but not others. Electrophoresis mobility shift assay (EMSA) and Chromatin immunoprecipitation (ChIP) assay demonstrated the direct binding of EGR1/3 transcription factors with ASMase 5′-promoter. These results indicate that increased EGR1/3 and ASMase expression play an important role in cellular ceramide increase by RSV treatment. - Highlights: • Resveratrol inhibited cell proliferation of K562 and HCT116 cells. • Resveratrol increased cellular ceramide and decreased sphingomyelin and S1P. • ASMase mRNA and activity were increased with resveratrol. • ASMase inhibition suppressed RSV-induced ceramide accumulation. • Increased ASMase transcription was at least partially due to EGR family proteins.

Ontogenic studies of the neural control of adenohypophyseal hormones in the rat. II. Prolactin.

Science.gov (United States)

Becú-Villalobos, D; Lacau-Mengido, I M; Díaz-Torga, G S; Libertun, C

1992-02-01

1. Serum prolactin levels are low during the first 20 days of life and gradually increase toward puberty, in both male and female rats. 2. There is an age-related increase in the cell population engaged in prolactin secretion, as well as an increase in the synthesis of prolactin and of the amount of prolactin secreted from individual lactotropes. 3. The gradual increase in prolactin levels in the third week of life is not related to a decrease in dopaminergic inhibition but to an increase in the efficiency of prolactin releasing factors such as estrogen, serotonin, opiates, and posterior pituitary extracts. 4. Prolactin release induced by physiological factors, such as stress, cervical stimulation, or the expression of spontaneous diurnal and nocturnal surges, requires maturational events within the hypothalamic-pituitary axis which are evident at the end of the third week of life. 5. In the female rat the steadily increasing levels of prolactin are involved in the timing of puberty eclosion acting at the ovary and at the brain. 6. In the prepubertal male rat increasing titers of prolactin may be involved in testicular and accessory organ development and may facilitate the actions of luteinizing hormone, follicle stimulating hormone, and testosterone on male sexual organs.

Urotensin II contributes to collagen synthesis and up-regulates Egr-1 expression in cultured pulmonary arterial smooth muscle cells through the ERK1/2 pathway

Energy Technology Data Exchange (ETDEWEB)

Li, Wei [Biomedical Engineering Institute, School of Control Science and Engineering, Shandong University, Jinan 250061 (China); Cai, Zhifeng; Liu, Mengmeng [Department of Pediatrics, Qilu Hospital, Shandong University, Jinan 250012 (China); Zhao, Cuifen, E-mail: zhaocuifen@sdu.edu.cn [Department of Pediatrics, Qilu Hospital, Shandong University, Jinan 250012 (China); Li, Dong [Research Room of Hypothermia Medicine, Qilu Hospital, Shandong University, Jinan 250012 (China); Lv, Chenguang; Wang, Yuping; Xu, Tengfei [Biomedical Engineering Institute, School of Control Science and Engineering, Shandong University, Jinan 250061 (China)

2015-11-27

Aim: The objective of this study was to investigate the effects of urotensin II (UII) treatment on the proliferation and collagen synthesis of cultured rat pulmonary arterial smooth muscle cells (PASMCs) and to explore whether these effects are mediated by mitogen-activated protein kinase (MAPK) signaling pathways and early growth response 1 (Egr-1). Methods: The proliferation of cultured PASMCs stimulated with different doses of UII was detected by BrdU incorporation. The mRNA expression levels of procollagen I (procol I), procollagen III (procol III), extracellular regulated protein kinase 1/2 (ERK1/2), stress-stimulated protein kinase (Sapk), p38 MAPK (p38), and Egr-1 mRNA in cultured PASMCs after treatment with UII, the UII-specific antagonist urantide, and the ERK1/2 inhibitor PD98059 were detected by real-time polymerase chain reaction (PCR), and the protein expression levels of procol I, procol III, phosphorylated (p)-ERK1/2, p-Sapk, p-p38, and Egr-1 were detected by Western blotting. Results: Treatment with UII increased the proliferation of cultured PASMCs in a dose-dependent manner (P < 0.05). However, treatment with urantide and PD98059 inhibited the promoting effect of UII on PASMC proliferation (P < 0.05). Real-time PCR analysis showed that UII up-regulated the expression of procol I, procol III, ERK1/2, Sapk, and Egr-1 mRNA (P < 0.05), but not p38 mRNA. However, the up-regulating effect of UII was inhibited by PD98059 and urantide. Western blotting analysis showed that UII increased the synthesis of collagen I, collagen III, p-ERK1/2, p-Sapk, and Egr-1, and these effects also were inhibited by PD98059 and urantide (P < 0.05). Conclusions: Egr-1 participates in the UII-mediated proliferation and collagen synthesis of cultured rat PASMCs via activation of the ERK1/2 signaling pathway.

Emission behavior of OH radical in internal EGR using a 2-cycle engine; 2 cycle engine wo mochiita naibu EGR no OH radical no hakko kyodo

Energy Technology Data Exchange (ETDEWEB)

Hashimoto, S; Amino, Y; Yoshida, K; Shoji, H; Saima, A [Nihon University, Tokyo (Japan)

1997-10-01

The purpose of this study was to examine and consider the influence, which the remained gas exercised on combustion. 2-cycle engine was Used as the test engine. Internal EGR was run. The means was that the test engine was fitted the back pressure control plate on the exhaust port. The conditions, which were run with internal EGR and without internal EGR, were compared. The OH radical, which plays important role in combustion of hydrocarbon fuels, was measured with emission spectroscopy. In internal EGR, the unburned end gas on exhaust port side was susceptible to the remained gas. 6 refs., 8 figs., 1 tab.

Context-Dependent Egr1 Expression in the Avian Hippocampus.

Science.gov (United States)

Grella, Stephanie L; Guigueno, Mélanie F; White, David J; Sherry, David F; Marrone, Diano F

2016-01-01

In mammals, episodic memory and spatial cognition involve context-specific recruitment of unique ensembles in the hippocampal formation (HF). Despite their capacity for sophisticated spatial (e.g., for migration) and episodic-like (e.g., for food-caching) memory, the mechanisms underlying contextual representation in birds is not well understood. Here we demonstrate environment-specific Egr1 expression as male brown-headed cowbirds (Molothrus ater) navigate environments for food reward, showing that the avian HF, like its mammalian counterpart, recruits distinct neuronal ensembles to represent different contexts.

Honey bee foraging induces upregulation of early growth response protein 1, hormone receptor 38 and candidate downstream genes of the ecdysteroid signalling pathway.

Science.gov (United States)

Singh, A S; Shah, A; Brockmann, A

2018-02-01

In honey bees, continuous foraging at an artificial feeder induced a sustained upregulation of the immediate early genes early growth response protein 1 (Egr-1) and hormone receptor 38 (Hr38). This gene expression response was accompanied by an upregulation of several Egr-1 candidate downstream genes: ecdysone receptor (EcR), dopamine/ecdysteroid receptor (DopEcR), dopamine decarboxylase and dopamine receptor 2. Hr38, EcR and DopEcR are components of the ecdysteroid signalling pathway, which is highly probably involved in learning and memory processes in honey bees and other insects. Time-trained foragers still showed an upregulation of Egr-1 when the feeder was presented at an earlier time of the day, suggesting that the genomic response is more dependent on the food reward than training time. However, presentation of the feeder at the training time without food was still capable of inducing a transient increase in Egr-1 expression. Thus, learnt feeder cues, or even training time, probably affect Egr-1 expression. In contrast, whole brain Egr-1 expression changes did not differ between dancing and nondancing foragers. On the basis of our results we propose that food reward induced continuous foraging ultimately elicits a genomic response involving Egr-1 and Hr38 and their downstream genes. Furthermore this genomic response is highly probably involved in foraging-related learning and memory responses. © 2017 The Royal Entomological Society.

Modulating effect of the nootropic drug, piracetam on stress- and subsequent morphine-induced prolactin secretion in male rats.

OpenAIRE

Matton, A.; Engelborghs, S.; Bollengier, F.; Finné, E.; Vanhaeist, L.

1996-01-01

1. The effect of the nootropic drug, piracetam on stress- and subsequent morphine-induced prolactin (PRL) secretion was investigated in vivo in male rats, by use of a stress-free blood sampling and drug administration method by means of a permanent indwelling catheter in the right jugular vein. 2. Four doses of piracetam were tested (20, 100, 200 and 400 mg kg-1), being given intraperitoneally 1 h before blood sampling; control rats received saline instead. After a first blood sample, rats we...

Are sexual side effects of prolactin-raising antipsychotics reducible to serum prolactin?

NARCIS (Netherlands)

Knegtering, Henderikus; van den Bosch, Rob; Castelein, Stynke; Bruggeman, Richard; Sytema, Sjoerd; van Os, Jim

Objective: To assess the degree to which sexual side effects (SSE) are associated with prolactin-raising antipsychotics, and to what degree such SSE are reducible to serum prolactin levels. Method: A large sample (n = 264) of patients treated for 6 weeks with protactin-raising and prolactin-sparing

Sex differences in the hypothalamic control of prolactin secretion

International Nuclear Information System (INIS)

Grattan, D.R.; Liu, L.; Bunn, S.J.

2001-01-01

Full text: Sex differences in the brain may arise from the organisational effects of exposure to sex steroids during development, or from the exposure to a differential hormonal milieu in the adult. There is a marked sex difference in the neuroendocrine mechanism that regulates prolactin secretion. Levels of prolactin in the blood are higher in females than in males. Similarly, basal activity of tuberoinfundibular dopamine (TIDA) neurons, which are involved in the tonic suppression of prolactin secretion, are two fold higher in females than in males. Prolactin is known to stimulate the activity of TIDA neurons, thereby regulating its own secretion by short-loop feedback. Hence, it is thought that elevated TIDA neuronal activity in females is induced by increased prolactin in the blood. We have recently demonstrated that prolactin stimulation of TIDA neurons requires the transcription factor, STAT5b. We have now investigated prolactin secretion in male and female STAT5b-deficient mice, to test the hypothesis that sex differences in TIDA neuronal activity are dependent on stimulation by prolactin acting through STAT5b. Prolactin levels in blood were measured by radioimmunoassay, and TIDA activity was assessed by measuring concentrations of the dopamine metabolite DOPAC in the median eminence by HPLC, and by measuring tyrosine hydroxylase mRNA in the arcuate nucleus by real-time RT-PCR. The data demonstrate marked gender differences in the activity of TIDA neurons. While TIDA activity in STAT5b-deficient mice was reduced compared to wild type, the sex difference persisted. Since STAT5b is required for the actions of prolactin on these neurons, we can conclude that the sexual dimorphism in brain function is independent of gender differences in blood levels of prolactin. It seems likely that differential exposure to gonadal steroid hormones, either during development or in adulthood, might underlie the sex difference in TIDA neuronal activity. Copyright (2001

Prolactin suppresses a progestin-induced CK5-positive cell population in luminal breast cancer through inhibition of progestin-driven BCL6 expression

Science.gov (United States)

Sato, Takahiro; Tran, Thai H.; Peck, Amy R.; Girondo, Melanie A.; Liu, Chengbao; Goodman, Chelain R.; Neilson, Lynn M.; Freydin, Boris; Chervoneva, Inna; Hyslop, Terry; Kovatich, Albert J.; Hooke, Jeffrey A.; Shriver, Craig D.; Fuchs, Serge Y.; Rui, Hallgeir

2014-01-01

Prolactin controls the development and function of milk-producing breast epithelia but also supports growth and differentiation of breast cancer, especially luminal subtypes. A principal signaling mediator of prolactin, Stat5, promotes cellular differentiation of breast cancer cells in vitro, and loss of active Stat5 in tumors is associated with anti-estrogen therapy failure in patients. In luminal breast cancer progesterone induces a cytokeratin-5 (CK5)-positive basal cell-like population. This population possesses characteristics of tumor stem cells including quiescence, therapy-resistance, and tumor-initiating capacity. Here we report that prolactin counteracts induction of the CK5-positive population by the synthetic progestin R5020 in luminal breast cancer cells both in vitro and in vivo. CK5-positive cells were chemoresistant as determined by four-fold reduced rate of apoptosis following docetaxel exposure. Progestin-induction of CK5 was preceded by marked up-regulation of BCL6, an oncogene and transcriptional repressor critical for the maintenance of leukemia-initiating cells. Knockdown of BCL6 prevented induction of CK5-positive cell population by progestin. Prolactin suppressed progestin-induced BCL6 through Jak2-Stat5 but not Erk- or Akt-dependent pathways. In premenopausal but not postmenopausal patients with hormone receptor-positive breast cancer, tumor protein levels of CK5 correlated positively with BCL6, and high BCL6 or CK5 protein levels were associated with unfavorable clinical outcome. Suppression of progestin-induction of CK5-positive cells represents a novel pro-differentiation effect of prolactin in breast cancer. The present progress may have direct implications for breast cancer progression and therapy since loss of prolactin receptor-Stat5 signaling occurs frequently and BCL6 inhibitors currently being evaluated for lymphomas may have value for breast cancer. PMID:23708665

Variation in social relationships relates to song preferences and EGR1 expression in a female songbird.

Science.gov (United States)

Schubloom, Hannah E; Woolley, Sarah C

2016-09-01

Social experiences can profoundly shape social behavior and the underlying neural circuits. Across species, the formation of enduring social relationships is associated with both neural and behavioral changes. However, it remains unclear how longer-term relationships between individuals influence brain and behavior. Here, we investigated how variation in social relationships relates to variation in female preferences for and neural responses to song in a pair-bonding songbird. We assessed variation in the interactions between individuals in male-female zebra finch pairs and found that female preferences for their mate's song were correlated with the degree of affiliation and amount of socially modulated singing, but not with the frequency of aggressive interactions. Moreover, variation in measures of pair quality and preference correlated with variation in the song-induced expression of EGR1, an immediate early gene related to neural activity and plasticity, in brain regions important for auditory processing and social behavior. For example, females with weaker preferences for their mate's song had greater EGR1 expression in the nucleus Taeniae, the avian homologue of the mammalian medial amygdala, in response to playback of their mate's courtship song. Our data indicate that the quality of social interactions within pairs relates to variation in song preferences and neural responses to ethologically relevant stimuli and lend insight into neural circuits sensitive to social information. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1029-1040, 2016. © 2016 Wiley Periodicals, Inc.

Histone H1 and Chromosomal Protein HMGN2 Regulate Prolactin-induced STAT5 Transcription Factor Recruitment and Function in Breast Cancer Cells.

Science.gov (United States)

Schauwecker, Suzanne M; Kim, J Julie; Licht, Jonathan D; Clevenger, Charles V

2017-02-10

The hormone prolactin (PRL) contributes to breast cancer pathogenesis through various signaling pathways, one of the most notable being the JAK2/signal transducer and activator of transcription 5 (STAT5) pathway. PRL-induced activation of the transcription factor STAT5 results in the up-regulation of numerous genes implicated in breast cancer pathogenesis. However, the molecular mechanisms that enable STAT5 to access the promoters of these genes are not well understood. Here, we show that PRL signaling induces chromatin decompaction at promoter DNA, corresponding with STAT5 binding. The chromatin-modifying protein high mobility group nucleosomal binding domain 2 (HMGN2) specifically promotes STAT5 accessibility at promoter DNA by facilitating the dissociation of the linker histone H1 in response to PRL. Knockdown of H1 rescues the decrease in PRL-induced transcription following HMGN2 knockdown, and it does so by allowing increased STAT5 recruitment. Moreover, H1 and STAT5 are shown to function antagonistically in regulating PRL-induced transcription as well as breast cancer cell biology. While reduced STAT5 activation results in decreased PRL-induced transcription and cell proliferation, knockdown of H1 rescues both of these effects. Taken together, we elucidate a novel mechanism whereby the linker histone H1 prevents STAT5 binding at promoter DNA, and the PRL-induced dissociation of H1 mediated by HMGN2 is necessary to allow full STAT5 recruitment and promote the biological effects of PRL signaling. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Modifying intake flow to increase EGR tolerance in an Internal Combustion Engine

Science.gov (United States)

Rubio, Daniel; Drabo, Mebougna; Puzinauskas, Paul

2010-11-01

The worldwide effort to reduce vehicle emissions and increase fuel efficiencies has continuously intensified as the need to improve air quality and reduce fuel consumption becomes more acute. Exhaust gas recirculation (EGR) is a method that has long been employed to reduce combustion temperatures and therefore reduce thermal NOx formation and accommodate higher compression ratios and more optimum combustion phasing for improved efficiency. Generally the effective EGR level as a percent of trapped charge is limited by its affect on combustion stability. Inducing flow structures such as swirl, squish and tumble in the trapped charge have proven to extend this EGR limit in homogeneous charge spark-ignited engines at part load, but this enhancement has not been significantly studied at full loads in such engines. This research explored modifying the intake flow into an engine to create tumble and evaluate its effect at high loads in such engines. This exploration included characterizing the flow on a steady flow bench and quantifying the results using engine dynamometer tests.

The Beckman DxI 800 prolactin assay demonstrates superior specificity for monomeric prolactin.

LENUS (Irish Health Repository)

Byrne, Brendan

2010-02-01

Commercially available prolactin immunoassays detect macroprolactin to variable degrees. Best practice requires laboratories to assess the cross-reactivity of their prolactin assay with macroprolactin, and where appropriate, introduce a screen for the presence of macroprolactin. Our policy has been to reanalyse hyperprolactinaemic samples following polyethylene glycol (PEG) precipitation and to report the resultant value as the monomeric prolactin content of the sample. The goal of this study was to determine the need to continue PEG precipitation when prolactin measurements with the Wallac AutoDELFIA were replaced by the Beckman DxI 800.

Prolactin blood test

Science.gov (United States)

... page: //medlineplus.gov/ency/article/003718.htm Prolactin blood test To use the sharing features on this page, ... test measures the amount of prolactin in the blood. How the Test is Performed A blood sample is needed . How ...

Effects of short- and long-term risperidone treatment on prolactin levels in children with autism.

Science.gov (United States)

Anderson, George M; Scahill, Lawrence; McCracken, James T; McDougle, Christopher J; Aman, Michael G; Tierney, Elaine; Arnold, L Eugene; Martin, Andrés; Katsovich, Liliya; Posey, David J; Shah, Bhavik; Vitiello, Benedetto

2007-02-15

The effects of short- and long-term risperidone treatment on serum prolactin were assessed in children and adolescents with autism. Patients with autism (N = 101, 5-17 years of age) were randomized to an 8-week trial of risperidone or placebo and 63 then took part in a 4-month open-label follow-up phase. Serum samples were obtained at Baseline and Week-8 (N = 78), and at 6-month (N = 43) and 22-month (N = 30) follow-up. Serum prolactin was determined by immunoradiometric assay; dopamine type-2 receptor (DRD2) polymorphisms were genotyped. Baseline prolactin levels were similar in the risperidone (N = 42) and placebo (N = 36) groups (9.3 +/- 7.5 and 9.3 +/- 7.6 ng/ml, respectively). After 8 weeks of risperidone, prolactin increased to 39.0 +/- 19.2 ng/ml, compared with 10.1 +/- 8.8 ng/ml for placebo (p autism. Although risperidone-induced increases tended to diminish with time, further research on the consequences of long-term prolactin elevations in children and adolescents is needed.

Numerical investigation of a dual-loop EGR split strategy using a split index and multi-objective Pareto optimization

International Nuclear Information System (INIS)

Park, Jungsoo; Song, Soonho; Lee, Kyo Seung

2015-01-01

Highlights: • Model-based control of dual-loop EGR system is performed. • EGR split index is developed to provide non-dimensional index for optimization. • EGR rates are calibrated using EGR split index at specific operating conditions. • Multi-objective Pareto optimization is performed to minimize NO X and BSFC. • Optimum split strategies are suggested with LP-rich dual-loop EGR at high load. - Abstract: A proposed dual-loop exhaust-gas recirculation (EGR) system that combines the features of high-pressure (HP) and low-pressure (LP) systems is considered a key technology for improving the combustion behavior of diesel engines. The fraction of HP and LP flows, known as the EGR split, for a given dual-loop EGR rate play an important role in determining the engine performance and emission characteristics. Therefore, identifying the proper EGR split is important for the engine optimization and calibration processes, which affect the EGR response and deNO X efficiencies. The objective of this research was to develop a dual-loop EGR split strategy using numerical analysis and one-dimensional (1D) cycle simulation. A control system was modeled by coupling the 1D cycle simulation and the control logic. An EGR split index was developed to investigate the HP/LP split effects on the engine performance and emissions. Using the model-based control system, a multi-objective Pareto (MOP) analysis was used to minimize the NO X formation and fuel consumption through optimized engine operating parameters. The MOP analysis was performed using a response surface model extracted from Latin hypercube sampling as a fractional factorial design of experiment. By using an LP rich dual-loop EGR, a high EGR rate was attained at low, medium, and high engine speeds, increasing the applicable load ranges compared to base conditions

Serum prolactin revisited

DEFF Research Database (Denmark)

Overgaard, Martin; Pedersen, Susanne Møller

2017-01-01

regimes across commonly used automated immunoassay platforms. METHODS: Parametric total and monomeric gender-specific reference intervals were determined for six immunoassay methods using female (n=96) and male sera (n=127) from healthy donors. The reference intervals were validated using 27...... and macroprolactinemic; n=27) showed higher discordant classification [mean=2.8; 95% confidence interval (CI) 1.2-4.4] for the monomer reference interval method compared to the post-polyethylene glycol (PEG) recovery cutoff method (mean=1.8; 95% CI 0.8-2.8). The two monomer/macroprolactin discrimination methods did...... not differ significantly (p=0.089). Among macroprolactinemic sera evaluated by both discrimination methods, the Cobas and Architect/Kryptor prolactin assays showed the lowest and the highest number of misclassifications, respectively. CONCLUSIONS: Current automated immunoassays for prolactin testing require...

Effects of light deprivation on prolactin regulation in the Golden Syrian hamster

International Nuclear Information System (INIS)

Massa, J.S.

1986-01-01

Pineal-mediated depressions in prolactin cell activity after light deprivation were studied in the male and female Golden Syrian hamster. Prolactin cell activity was determined by measuring radioimmunoassayable prolactin, newly synthesized prolactin, newly synthesized prolactin and prolactin mRNA levels in the pituitary. Serum prolactin was also measured by radioimmunoassay. Use of the recombinant DNA plasmid, pPRL-1, which contains the rat prolactin complimentary DNA sequence, was validated in this dissertation for measuring prolactin mRNA in the hamster. Male Hamsters blinded for 11, 21, or 42 days showed significant and progressively greater declines in prolactin mRNA levels which were completely prevented by pinealectomy. Female hamsters blinded for 28 days, however, showed no such decreases in prolactin cell activity if they continued to display estrous cyclicity. After 12 weeks of blinding, females were acyclic and had dramatically depressed levels of prolactin cell activity. However, pinealectomy did not completely prevent this decline due to blinding unless the females continue to display estrous cyclicity. In ovariectomized females, blinding caused a decline in prolactin cell activity. In a separate study, significant changes in prolactin cell activity during the estrous cycle were seen in untreated normally cycling female hamsters. These changes in prolactin mRNA, prolactin synthesis, and radioimmunoassayable prolactin in the pituitary were measured in the morning, when, consistent with other reports, no differences in serum prolactin were observed

Mechanisms of dietary response in mice and primates: a role for EGR1 in regulating the reaction to human-specific nutritional content.

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Kai Weng

Full Text Available Humans have a widely different diet from other primate species, and are dependent on its high nutritional content. The molecular mechanisms responsible for adaptation to the human diet are currently unknown. Here, we addressed this question by investigating whether the gene expression response observed in mice fed human and chimpanzee diets involves the same regulatory mechanisms as expression differences between humans and chimpanzees.Using mouse and primate transcriptomic data, we identified the transcription factor EGR1 (early growth response 1 as a putative regulator of diet-related differential gene expression between human and chimpanzee livers. Specifically, we predict that EGR1 regulates the response to the high caloric content of human diets. However, we also show that close to 90% of the dietary response to the primate diet found in mice, is not observed in primates. This might be explained by changes in tissue-specific gene expression between taxa.Our results suggest that the gene expression response to the nutritionally rich human diet is partially mediated by the transcription factor EGR1. While this EGR1-driven response is conserved between mice and primates, the bulk of the mouse response to human and chimpanzee dietary differences is not observed in primates. This result highlights the rapid evolution of diet-related expression regulation and underscores potential limitations of mouse models in dietary studies.

Importance of prolactin for lactation in the ewe

Energy Technology Data Exchange (ETDEWEB)

Hooley, R D; Campbell, J J; Findlay, J K [Reproduction Research Section, Melbourne Univ., C/- Animal Research Inst., Werribee (Australia)

1978-12-01

The effect of 2-bromo-..cap alpha..-ergocryptine (bromocriptine) on the induction and maintenance of milk secretion was studied in post-parturient ewes and in ovariectomized ewes artificially induced to lactate by treatment with oestrogen plus progesterone and then dexamethasone. Treatment with bromocriptine (about 0.4 mk/kg every 3 days) lowered and maintained the plasma concentration of prolactin at < 12 ng/ml. Ewes receiving bromocriptine concurrently with oestrogen plus progesterone during the priming phase had a significantly lower (P < 0.05) mean cumulative milk yield than control ewes, although the milk of the treated ewes contained normal amounts of fat, protein and lactose. Administration of bromocriptine during dexamethasone-induced lactogenesis had no significant effect on the mean cumulative milk yield but significantly (P < 0.05) increased the milk fat and protein content. In establishing lactation, bromocriptine markedly reduced the milk yield in both intact and ovariectomised ewes. The concentration of protein was not significantly affected although the milk fat content was higher in the bromocriptine-treated than in the control ewes. The effects of bromocriptine on milk yield and composition during galactopoiesis could be reversed by concurrent infusion of prolactin and the results suggest that prolactin is an important hormone during mammogenesis and galactopoiesis in sheep.

Early growth response gene-2 (Egr-2 regulates the development of B and T cells.

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Suling Li

2011-04-01

Full Text Available Understanding of how transcription factors are involved in lymphocyte development still remains a challenge. It has been shown that Egr-2 deficiency results in impaired NKT cell development and defective positive selection of T cells. Here we investigated the development of T, B and NKT cells in Egr-2 transgenic mice and the roles in the regulation of distinct stages of B and T cell development.The expression of Egr1, 2 and 3 were analysed at different stages of T and B cell development by RT-PCT and results showed that the expression was strictly regulated at different stages. Forced expression of Egr-2 in CD2(+ lymphocytes resulted in a severe reduction of CD4(+CD8(+ (DP cells in thymus and pro-B cells in bone marrow, which was associated with reduced expression of Notch1 in ISP thymocytes and Pax5 in pro-B cells, suggesting that retraction of Egr-2 at the ISP and pro-B cell stages is important for the activation of lineage differentiation programs. In contrast to reduction of DP and pro-B cells, Egr-2 enhanced the maturation of DP cells into single positive (SP T and NKT cells in thymus, and immature B cells into mature B cells in bone marrow.Our results demonstrate that Egr-2 expressed in restricted stages of lymphocyte development plays a dynamic, but similar role for the development of T, NKT and B cells.

A pigeon crop sac radioreceptor assay for prolactin

International Nuclear Information System (INIS)

Forsyth, I.A.; Buntin, J.D.; Nicoll, C.S.

1978-01-01

Ovine prolactin, labelled with 125 I by either lactoperoxidase or a mild chloramine T method, was bound to receptors from the pigeon crop sac mucosa cells of prolactin-injected pigeons. Binding was demonstrated in a crude homogenate of mucosal cells removed from the crop by scraping and in a subcellular fraction in which 5'- nucleotidase activity was enhanced two- to three-fold. The binding was specific, dependent on time, temperature and the concentration of receptors and had a dissociation constant of 7 x 10 -10 mol/l. The binding capacity of the crop tissue was 71 fmol/mg membrane protein. Nine purified preparations of prolactin from four species were assayed by local pigeon crop sac bioassay and by radioreceptor assay. The two methods were highly correlated (r = 0.934). The regression equation was radioreceptor assay = 1.22 bioassay - 0.18 indicating a 1:1 correspondence between the two methods for prolactin purified from sheep, rat, horse and pig anterior pituitary glands. (author)

Study on the Combustion Process and Emissions of a Turbocharged Diesel Engine with EGR

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Mei Deqing

2012-01-01

Full Text Available A high pressure EGR system was adopted to a turbocharged inter-cooled diesel engine, to analyze its combustion and emission characteristics under the condition of different loads and constant speed. Under the same steady operating mode, with the increase of EGR rate, the temperature of compressed gas ascended, the ignition delay was shortened, the pressure and temperature of the burned gas descended, and the combustion process was prolonged. According to the experimental data, it was found that, at the same EGR rate, lower the load of engine was, lower the temperature in cylinder, and higher the increase rate of CO was. However, the increase rate of HC present a falling trend. The decrease rate of the specific emission of NOx linearly varied with EGR rate with a slope of 1.651. The increase rate of smoke opacity behaved a second-order polynomial uprising trend, and the higher the load was, the sharpener the smoke opacity deteriorated, with the increase of EGR rate. From the point of emission view, the engine with EGR system can achieve the lesser exhaust emissions in some operations by adjusting the engine parameters.

Obtention of antibodies anti prolactin from human prolactin of national production

International Nuclear Information System (INIS)

Caso, R.; Mosquera, M.; Perez, E.; Amanz, C.

1996-01-01

In this work was studied the use of the the Prolactin hormone as immuno gen, which is obtained in Cuba by the pharmaceutical institute Mario Munoz, to produce the antibody antiprolactin. Was made the validation of obtained antibody (tritatium, specificity and affinity) The produced antibody had necessary quality to be use as a component of the Kits-RIA Prolactin

The prolactin response to an acute stressor in relation to parental care and corticosterone in a short-lived bird, the Eurasian hoopoe.

Science.gov (United States)

Schmid, Baptiste; Chastel, Olivier; Jenni, Lukas

2011-10-01

Prolactin plays an important role in mediating parental care in birds, but little is known about changes in prolactin levels when animals disrupt their reproductive behaviour during emergency life-history stages. We investigated the variation of prolactin levels with breeding stage, sex, body condition and as a response to a standardized acute stressor in a small short-lived bird, the Eurasian hoopoe Upupa epops under natural field conditions. We found higher baseline levels of prolactin in females during the brooding phase than in their mates which feed them and their chicks at this stage. Moreover, this is the first report of a differential prolactin stress-response between sexes with contrasting parental care within a breeding phase. Capture, handling and restraint induced a clear decrease of prolactin levels which was less pronounced in females at the very early stage of brooding compared to females in later stages. In contrast, the prolactin stress response in males remained nearly constant over the breeding stages and was stronger than in females. Baseline levels of prolactin, but not handling-induced levels, were positively correlated with body condition. We found a weak relationship between the decrease in prolactin due to acute handling stress and handling-induced levels of corticosterone. Taken together, both baseline and stress response levels of prolactin were related to the amount of parental care, although we found no relationship with reproductive success. It appears that the response to an acute stressor in prolactin levels is finely tuned to parental duties and investment. Hence, prolactin appears to be involved in mediating the trade-off between current reproduction versus self-maintenance and future reproduction. Copyright © 2011 Elsevier Inc. All rights reserved.

Serum prolactin level in patients taking olanzapine

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Diganta Das

2015-01-01

Full Text Available Introduction: Olanzapine is a commonly used antipsychotic. Prolactin elevation is a common adverse effect of anstipsychotics, and serum prolactin elevation is seen in about 30% patients treated with olanzapine. There are confounding results about dose dependency of olanzapine and prolactin elevation, and also the duration of treatment. Method: Fifty six patients, 36 male and 20 female, who were taking olanzapine for any condition for more than a month at a constant dose were enrolled in the study. Patients’ age, weight, body mass index (BMI, serum prolactin levels, and some biochemical values were recorded. Patients were taken from the review outpatient department (OPD after due consent. Results: Five each in male and female groups showed elevation of serum prolactin (estimated to be high if >20 ng/dl for males, and >25 ng/dl for females. In females, the elevation was found at lesser dose of olanzapine (13 mg/day, in males 18 mg/day and early in the treatment (2.4 months vs. 9.7 months in males. Males tended to show raised prolactin with higher doses of olanzapine (mean 18 mg/day. Females (26.31% also showed higher prevalence of prolactin elevation compared to males (13.51%. No other parameter was found to modify the prolactin levels. Conclusion: Olanzapine causes elevation of serum prolactin, though lesser degree than some other antipsychotics. Females are more prone to have raised serum prolactin with olanzapine compared to males. However, the elevation seems to be transient. Higher doses of olanzapine tend to cause elevation of serum prolactin. Serum prolactin estimation in patients taking olanzapine may be undertaken to maintain quality life, particularly in females.

N-terminal prolactin-derived fragments, vasoinhibins, are proapoptoptic and antiproliferative in the anterior pituitary.

Science.gov (United States)

Ferraris, Jimena; Radl, Daniela Betiana; Zárate, Sandra; Jaita, Gabriela; Eijo, Guadalupe; Zaldivar, Verónica; Clapp, Carmen; Seilicovich, Adriana; Pisera, Daniel

2011-01-01

The anterior pituitary is under a constant cell turnover modulated by gonadal steroids. In the rat, an increase in the rate of apoptosis occurs at proestrus whereas a peak of proliferation takes place at estrus. At proestrus, concomitant with the maximum rate of apoptosis, a peak in circulating levels of prolactin is observed. Prolactin can be cleaved to different N-terminal fragments, vasoinhibins, which are proapoptotic and antiproliferative factors for endothelial cells. It was reported that a 16 kDa vasoinhibin is produced in the rat anterior pituitary by cathepsin D. In the present study we investigated the anterior pituitary production of N-terminal prolactin-derived fragments along the estrous cycle and the involvement of estrogens in this process. In addition, we studied the effects of a recombinant vasoinhibin, 16 kDa prolactin, on anterior pituitary apoptosis and proliferation. We observed by Western Blot that N-terminal prolactin-derived fragments production in the anterior pituitary was higher at proestrus with respect to diestrus and that the content and release of these prolactin forms from anterior pituitary cells in culture were increased by estradiol. A recombinant preparation of 16 kDa prolactin induced apoptosis (determined by TUNEL assay and flow cytometry) of cultured anterior pituitary cells and lactotropes from ovariectomized rats only in the presence of estradiol, as previously reported for other proapoptotic factors in the anterior pituitary. In addition, 16 kDa prolactin decreased forskolin-induced proliferation (evaluated by BrdU incorporation) of rat total anterior pituitary cells and lactotropes in culture and decreased the proportion of cells in S-phase of the cell cycle (determined by flow cytometry). In conclusion, our study indicates that the anterior pituitary production of 16 kDa prolactin is variable along the estrous cycle and increased by estrogens. The antiproliferative and estradiol-dependent proapoptotic actions of this

N-terminal prolactin-derived fragments, vasoinhibins, are proapoptoptic and antiproliferative in the anterior pituitary.

Directory of Open Access Journals (Sweden)

Jimena Ferraris

Full Text Available The anterior pituitary is under a constant cell turnover modulated by gonadal steroids. In the rat, an increase in the rate of apoptosis occurs at proestrus whereas a peak of proliferation takes place at estrus. At proestrus, concomitant with the maximum rate of apoptosis, a peak in circulating levels of prolactin is observed. Prolactin can be cleaved to different N-terminal fragments, vasoinhibins, which are proapoptotic and antiproliferative factors for endothelial cells. It was reported that a 16 kDa vasoinhibin is produced in the rat anterior pituitary by cathepsin D. In the present study we investigated the anterior pituitary production of N-terminal prolactin-derived fragments along the estrous cycle and the involvement of estrogens in this process. In addition, we studied the effects of a recombinant vasoinhibin, 16 kDa prolactin, on anterior pituitary apoptosis and proliferation. We observed by Western Blot that N-terminal prolactin-derived fragments production in the anterior pituitary was higher at proestrus with respect to diestrus and that the content and release of these prolactin forms from anterior pituitary cells in culture were increased by estradiol. A recombinant preparation of 16 kDa prolactin induced apoptosis (determined by TUNEL assay and flow cytometry of cultured anterior pituitary cells and lactotropes from ovariectomized rats only in the presence of estradiol, as previously reported for other proapoptotic factors in the anterior pituitary. In addition, 16 kDa prolactin decreased forskolin-induced proliferation (evaluated by BrdU incorporation of rat total anterior pituitary cells and lactotropes in culture and decreased the proportion of cells in S-phase of the cell cycle (determined by flow cytometry. In conclusion, our study indicates that the anterior pituitary production of 16 kDa prolactin is variable along the estrous cycle and increased by estrogens. The antiproliferative and estradiol-dependent proapoptotic

Mean Value Modelling of an SI Engine with EGR

DEFF Research Database (Denmark)

Føns, Michael; Muller, Martin; Chevalier, Alain

1999-01-01

Mean Value Engine Models (MVEMs) are simplified, dynamic engine models which are physically based. Such models are useful for control studies, for engine control system analysis and for model based control systems. Very few published MVEMs have included the effects of Exhaust Gas Recirculation (EGR......). The purpose of this paper is to present a modified MVEM which includes EGR in a physical way. It has been tested using newly developed, ver fast manifold pressure, manifold temperature, port and EGR mass flow sensores. Reasonable agreement has been obtained on an experimental engine, mounted on a dynamometer....

Clinical indications of prolactin radioimmunoassay

International Nuclear Information System (INIS)

Lengyel, A.M.J.; Vieira, J.G.H.; Zanella, M.R.; Zampieri, M.; Chacra, A.R.

1980-01-01

Is a review is presented of the main clinical uses of prolactin measurements, including the galactorrhea-amenorrhea syndrome, an experiment employing the prolactin radioimmunoassay is related. (Author) [pt

Cadmium mimics estrogen-driven cell proliferation and prolactin secretion from anterior pituitary cells.

Directory of Open Access Journals (Sweden)

Sonia A Ronchetti

Full Text Available Cadmium (Cd is a heavy metal of considerable occupational and environmental concern affecting wildlife and human health. Recent studies indicate that Cd, like other heavy metals, can mimic effects of 17β-estradiol (E2 involving E2 receptor (ER activation. Lactotrophs, the most abundant cell type in anterior pituitary gland, are the main target of E2, which stimulates cell proliferation and increases prolactin secretion through ERα. The aim of this work was to examine whether Cd at nanomolar concentrations can induce cell proliferation and prolactin release in anterior pituitary cells in culture and whether these effects are mediated through ERs. Here we show that 10 nM Cd was able to stimulate lactotroph proliferation in anterior pituitary cell cultures from female Wistar rats and also in GH3 lactosomatotroph cell line. Proliferation of somatotrophs and gonadotrophs were not affected by Cd exposure. Cd promoted cell cycle progression by increasing cyclins D1, D3 and c-fos expression. Cd enhanced prolactin synthesis and secretion. Cd E2-like effects were blocked by the pure ERs antagonist ICI 182,780 supporting that Cd acts through ERs. Further, both Cd and E2 augmented full-length ERαexpression and its 46 kDa-splicing variant. In addition, when co-incubated Cd was shown to interact with E2 by inducing ERα mRNA expression which indicates an additive effect between them. This study shows for the first time that Cd at nanomolar concentration displays xenoestrogenic activities by inducing cell growth and stimulating prolactin secretion from anterior pituitary cells in an ERs-dependent manner. Cd acting as a potent xenoestrogen can play a key role in the aetiology of different pathologies of the anterior pituitary and in estrogen-responsive tissues which represent considerable risk to human health.

The importance of prolactin for lactation in the ewe

International Nuclear Information System (INIS)

Hooley, R.D.; Campbell, J.J.; Findlay, J.K.

1978-01-01

The effect of 2-bromo-α-ergocryptine (bromocriptine) on the induction and maintenance of milk secretion was studied in post-parturient ewes and in ovariectomized ewes artificially induced to lactate by treatment with oestrogen plus progesterone and then dexamethasone. Treatment with bromocriptine (about 0.4 mk/kg every 3 days) lowered and maintained the plasma concentration of prolactin at < 12 ng/ml. Ewes receiving bromocriptine concurrently with oestrogen plus progesterone during the priming phase had a significantly lower (P < 0.05) mean cumulative milk yield than control ewes, although the milk of the treated ewes contained normal amounts of fat, protein and lactose. Administration of bromocriptine during dexamethasone-induced lactogenesis had no significant effect on the mean cumulative milk yield but significantly (P < 0.05) increased the milk fat and protein content. In establishing lactation, bromocriptine markedly reduced the milk yield in both intact and ovariectomised ewes. The concentration of protein was not significantly affected although the milk fat content was higher in the bromocriptine-treated than in the control ewes. The effects of bromocriptine on milk yield and composition during galactopoiesis could be reversed by concurrent infusion of prolactin and the results suggest that prolactin is an important hormone during mammogenesis and galactopoiesis in sheep. (author)

Pubertal dependent effects of cadmium on episodic prolactin secretion in male rats

Energy Technology Data Exchange (ETDEWEB)

Lafuente, A.; Alvarez-Demanuel, E.; Marquez, N. [Fac. de Cienicas, Orense (Spain). Lab. de Toxicologia; Esquifino, A.I. [Dept. Bioquimica, Facultad de Medicina, Universidad Complutense, 28040-Madrid (Spain)

1999-02-01

This work was undertaken to assess if exposure to cadmium related to puberty may affect the episodic pattern of prolactin. Male rats were submitted to cadmium exposure, from day 30 to 60 or from day 60 to 90 of life respectively, at a dose of 50 ppm in the drinking water. Control age-matched rats received cadmium-free water. Prepubertal cadmium administration decreased mean serum prolactin levels and the absolute amplitude of the prolactin pulses. Subchronic exposure to cadmium of adult rats decreased mean serum prolactin levels, the absolute amplitude of the prolactin pulses and their duration, and the mean half-life of the hormone. These results suggest that subchronic cadmium exposure changes the secretory pattern of prolactin in adult male rats in a puberty-dependent way. (orig.) With 1 fig., 1 tab., 37 refs.

[Plasma prolactin concentration and the effect of metergoline in pseudopregnant Afghan hounds].

Science.gov (United States)

Okkens, A C; Dieleman, S J; Kooistra, H S; Bevers, M M

2000-02-01

The effects of metergoline, a 5-hydroxytryptamine (serotinin) antagonist, on the plasma concentrations of prolactin in overtly pseudopregnant Afghan hounds and on the clinical symptoms of overt pseudopregnancy were studied. Plasma concentrations of prolactin and progesterone were determined in six Afghan hounds with signs of overt pseudopregnancy for 2-3 weeks and in three Afghan hounds that were not pseudopregnant at the time of blood sampling. In the overtly pseudopregnant bitches the plasma concentrations of prolactin before treatment (35.5 +/- 8.5 micrograms l-1) were significantly higher than the plasma concentrations of prolactin of the three bitches that were not pseudopregnant (6.3 +/- 0.5 micrograms l-1); the latter values were similar to those of non-psueodopregnant beagle bitches during the total luteal phase. The six pseudopregnant Afghan hounds were treated for 10 days with the antiserotoninergic drug metergoline. At 2 h after the onset of treatment with metergoline, the mean plasma concentration of prolactin had decreased to 10.8 +/- 2.9 micrograms l-1. The plasma concentrations of prolactin continued to decline to 5.4 +/- 1.0 micrograms l-1 at 4 h and to 1.0 +/- 0.1 microgram l-1 during treatment days 3-10. Signs of pseudopregnancy, such as swelling of the mammary glands and digging, decreased during the treatment period. The treatment was associated with mild behavioural side effects such as whimpering and aggressiveness. These side effects are probably not related to suppression of prolactin but are due to a direct effect on serotoninergic pathways in the brain. It is concluded that high plasma concentrations of prolactin are associated with the development and maintenance of pseudopregnancy. The serotonin antagonist metergoline strongly suppresses plasma concentration of prolactine in pseudopregnant dogs and decreases the clinical signs of pseudopregnancy.

Prolactin receptors in Rip-cre cells, but not in AgRP neurones, are involved in energy homeostasis.

Science.gov (United States)

Ladyman, S R; MacLeod, M A; Khant Aung, Z; Knowles, P; Phillipps, H R; Brown, R S E; Grattan, D R

2017-10-01

Among its many functions, prolactin has been implicated in energy homeostasis, particularly during pregnancy and lactation. The arcuate nucleus is a key site in the regulation of energy balance. The present study aimed to examine whether arcuate nucleus neuronal populations involved in energy homeostasis are prolactin responsive and whether they can mediate the effects of prolactin on energy homeostasis. To determine whether Agrp neurones or Rip-Cre neurones are prolactin responsive, transgenic mice expressing the reporter td-tomato in Agrp neurones (td-tomato/Agrp-Cre) or Rip-Cre neurones (td-tomato/Rip-Cre) were treated with prolactin and perfused 45 minutes later. Brains were processed for double-labelled immunohistochemistry for pSTAT5, a marker of prolactin-induced intracellular signalling, and td-tomato. In addition, Agrp-Cre mice and Rip-Cre mice were crossed with mice in which the prolactin receptor gene (Prlr) was flanked with LoxP sites (Prlr lox/lox mice). The Prlr lox/lox construct was designed such that Cre-mediated recombination resulted in deletion of the Prlr and expression of green fluorescent protein (GFP) in its place. In td-tomato/Rip-Cre mice, prolactin-induced pSTAT5 was co-localised with td-tomato, indicating that there is a subpopulation of Rip-Cre neurones in the arcuate nucleus that respond to prolactin. Furthermore, mice with a specific deletion of Prlr in Rip-Cre neurones had lower body weights, increased oxygen consumption, increased running wheel activity and numerous cells in the arcuate nucleus had positive GFP staining indicating deletion of Prlr from Rip-Cre neurones. By contrast, no co-localisation of td-tomato and pSTAT5 was observed in td-tomato/Agrp-Cre mice after prolactin treatment. Moreover, Prlr lox/lox /Agrp-Cre mice had no positive GFP staining in the arcuate nucleus and did not differ in body weight compared to littermate controls. Overall, these results indicate that Rip-Cre neurones in the arcuate nucleus are

Studies on the regulation of anuran metamorphosis by thyroid hormones and prolactin

International Nuclear Information System (INIS)

Ray, L.B.

1985-01-01

Resorption of the tail of the anuran larva during metamorphosis is induced by the thyroid hormones. In contrast, the pituitary hormone prolactin favors growth of the tail fin and inhibits resorption. The present investigations were designed to explore the mechanisms by which the thyroid hormones and prolactin bring about their cellular effects. Incubation of explants of tail fin with derivatives of cAMP was shown to inhibit T 4 -induced resorption of explants in a manner similar to that of prolactin. Likewise, inhibition of phosphodiesterases also inhibited resorption. Prolactin, however, failed to alter the levels of cAMP in cultured explants of tail fin. Although cAMP antagonizes the resorptive effects of T 4 , prolactin apparently does not act by elevating cellular levels of that cyclic nucleotide. Newly synthesized proteins from explants of tail fin were examined by isotopical labeling followed by two-dimensional gel electrophoresis and fluorography. Incorporation of 35 S-methionine into four proteins was increased within 8 to 48 hours after exposure of explants to T 4 . Three of the same proteins appeared to be synthesized more rapidly in explants of fin from tadpoles at metamorphic climax than in fin from tadpoles of premetamorphic stages. These results indicate that treatment of explants with T 4 or elevation of endogenous levels of thyroid hormones during spontaneous metamorphosis increased the relative rates of synthesis of several proteins. Those proteins are potentially involved in initiating the effects of T 4 which lead to cell death and resorption of the tail

System and method for regulating EGR cooling using a rankine cycle

Science.gov (United States)

Ernst, Timothy C.; Morris, Dave

2015-12-22

This disclosure relates to a waste heat recovery (WHR) system and method for regulating exhaust gas recirculation (EGR) cooling, and more particularly, to a Rankine cycle WHR system and method, including a recuperator bypass arrangement to regulate EGR exhaust gas cooling for engine efficiency improvement and thermal management. This disclosure describes other unique bypass arrangements for increased flexibility in the ability to regulate EGR exhaust gas cooling.

Transfer of milk prolactin ro the plasma of neonatal rats by intestinal absorption

Energy Technology Data Exchange (ETDEWEB)

Whitworth, N S; Grosvenor, C E [Tennessee Univ., Memphis (USA). Dept. of Physiology and Biophysics

1978-11-01

Prolactin passes from the systemic circulation of lactating rats into the milk where it can be consumed by the young rats during suckling. /sup 131/- labelled rat prolactin was detected in the plasma of 9- to 14-day-old rats after being nursed by mothers previously injected with /sup 131/I-labelled rat prolactin and after the pups had received /sup 131/I-labelled rat prolactin by gastric intubation. It was estimated that 16% of the /sup 131/I-labelled rat prolactin given by gastric intubation subsequently appeared in the plasma of the neonate. Gastric administration of 10.5 or 21.0 ..mu..g B-1 rat prolactin significantly raised the level of prolactin in the plasma of 13-day-old pups, but a similar increase was not observed when 27-day-old rats were given 46.2 ..mu..g B-1 prolactin by gastric intubation. The concentration of prolactin in the plasma of 13-to 14-day-old rats rose to 55 ng/ml 30 min after the onset of nursing by mothers whose mammary glands were full of milk, whereas the concentration in the plasma of mothers with empty mammary glands remained at basal values. It is concluded that the intestine of the newborn is permeable to prolactin and that milk may constitute an exogeneous source of prolactin for the suckled offspring.

Prolactin and teleost ionocytes: new insights into cellular and molecular targets of prolactin in vertebrate epithelia

Science.gov (United States)

Breves, Jason P.; McCormick, Stephen D.; Karlstrom, Rolf O.

2014-01-01

The peptide hormone prolactin is a functionally versatile hormone produced by the vertebrate pituitary. Comparative studies over the last six decades have revealed that a conserved function for prolactin across vertebrates is the regulation of ion and water transport in a variety of tissues including those responsible for whole-organism ion homeostasis. In teleost fishes, prolactin was identified as the “freshwater-adapting hormone”, promoting ion-conserving and water-secreting processes by acting on the gill, kidney, gut and urinary bladder. In mammals, prolactin is known to regulate renal, intestinal, mammary and amniotic epithelia, with dysfunction linked to hypogonadism, infertility, and metabolic disorders. Until recently, our understanding of the cellular mechanisms of prolactin action in fishes has been hampered by a paucity of molecular tools to define and study ionocytes, specialized cells that control active ion transport across branchial and epidermal epithelia. Here we review work in teleost models indicating that prolactin regulates ion balance through action on ion transporters, tight-junction proteins, and water channels in ionocytes, and discuss recent advances in our understanding of ionocyte function in the genetically and embryonically accessible zebrafish (Danio rerio). Given the high degree of evolutionary conservation in endocrine and osmoregulatory systems, these studies in teleost models are contributing novel mechanistic insight into how prolactin participates in the development, function, and dysfunction of osmoregulatory systems across the vertebrate lineage.

Prolactin levels during short- and long-term cross-sex hormone treatment: an observational study in transgender persons.

Science.gov (United States)

Nota, N M; Dekker, M J H J; Klaver, M; Wiepjes, C M; van Trotsenburg, M A; Heijboer, A C; den Heijer, M

2017-08-01

The cause of prolactin alterations in transgender persons is often assigned to oestrogens, but the precise cause and time course during different phases of cross-sex hormone treatment (CHT) remain unclear. In this study, we prospectively examined prolactin levels in 55 female-to-males (FtMs) and 61 male-to-females (MtFs) during the first year of CHT. Because long-term prolactin data were not available in this population, we studied these levels in a retrospective population of 25 FtMs and 38 MtFs who underwent gonadectomy. FtMs were treated with testosterone and MtFs with estradiol, with or without the anti-androgen cyproterone acetate (CPA) (after gonadectomy CPA is cessated). During the first year of CHT, prolactin decreased with 25% (95CI: -33%, -12%) in FtMs and increased with 193% (95CI: 156%, 219%) in MtFs. Eighteen MtFs developed hyperprolactinemia (≥0.6 IU L -1 ). In the retrospective population, post-gonadectomy levels in FtMs were lower than baseline levels (-39%; 95CI: -51%, -20%) while in MtFs post-gonadectomy levels and baseline levels were comparable (-6%; 95CI: -24%, 15%). No hyperprolactinemia was found after gonadectomy. In conclusion, in FtMs, prolactin decreased consistently during CHT and in MtFs, prolactin increased during pre-surgical CHT but normalised after gonadectomy. It is likely that CPA induces increasing prolactin levels in MtFs. © 2016 Blackwell Verlag GmbH.

Prolactin and aging: X-irradiated and estrogen-induced rat mammary tumorigenesis

International Nuclear Information System (INIS)

Ito, A.; Naito, M.; Watanabe, H.; Yokoro, K.

1984-01-01

Both sexes of inbred WF rats at either 8 or 28-60 weeks of age were exposed to 200 rad whole-body radiation, 2.5 or 5.0 mg 17 beta-estradiol (E2), or both agents The female rats treated with E2 alone or with both X-rays and E2 at 8 weeks of age showed a high incidence of mammary carcinomas (MCA), a large increase in pituitary weight, and a rise in serum prolactin (PRL) levels. However, the same treatments to males did not induce MCA despite a moderate increase in both pituitary weight and serum PRL. Ovariectomy prior to E2 treatment failed to modify the occurrence of MCA or pituitary tumors. When X-rays and E2 were given to female rats at 28-60 weeks of age, pituitary weight, serum PRL levels, and the incidence of MCA were unaffected. When the E2 pellet was kept for the first 24 weeks and withdrawn during the last 12 weeks, the incidence of MCA, pituitary weight, and serum PRL was low. It was concluded that: 1) the pituitary glands of young female rats were susceptible to E2 treatment but were insensitive in older females, and 2) the occurrence of MCA in female rats appeared to be promoted by elevated PRL levels secreted by E2-induced pituitary tumors. Mammary tissue of male rats was less sensitive to PRL levels in the development of MCA

Homologous radioimmunoassay for canine prolactin and its application in various physiological states

International Nuclear Information System (INIS)

Graef, K.-J.; Friedreich, E.; Matthes, S.; Hasan, S.H.

1977-01-01

The purification of canine prolactin and the development of an homologous radioimmunoassay including several physiological studies in the Beagle dog are described. The assay measured immunoreactive canine prolactin with a sensitivity limit of 0.6 ng/ml. Purified canine luteinizing hormone gave no significant inhibition in the assay whereas purified canine growth hormone inhibited the binding of 125 I-labelled canine prolactin to antiserum only at very high dose levels. In Beagle dogs, basal serum prolactin concentrations were in the range 1 to 2 ng/ml in normal male, normal female (metoestrus and anoestrus) and oophorectomized-hysterectomized female dogs. The prolactin concentration in one sample of amniotic fluid was in the same range, while in hypophysectomized make dogs no serum prolactin could be detected by the assay system. Serum prolactin concentrations tended to increase during late pregnancy and parturition, remaining high during the first 9 days of lactation. In consequence, a negative correlation was suggested between serum prolactin and serum progesterone concentrations. (author)

Mean Value Engine Modelling of an SI Engine with EGR

DEFF Research Database (Denmark)

Føns, Michael; Müller, Martin; Chevalier, Alain

1999-01-01

Mean Value Engine Models (MVEMs) are simplified, dynamic engine models what are physically based. Such models are useful for control studies, for engine control system analysis and for model based engine control systems. Very few published MVEMs have included the effects of Exhaust Gas...... Recirculation (EGR). The purpose of this paper is to present a modified MVEM which includes EGR in a physical way. It has been tested using newly developed, very fast manifold pressure, manifold temperature, port and EGR mass flow sensors. Reasonable agreement has been obtained on an experimental engine...

File list: Oth.Bld.50.Egr2.AllCell [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.Bld.50.Egr2.AllCell mm9 TFs and others Egr2 Blood SRX270570,SRX270569,SRX329255...,SRX110637,SRX110636,SRX329257,SRX329256,SRX122432,SRX122435,SRX122433,SRX122434 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Bld.50.Egr2.AllCell.bed ...

File list: Oth.ALL.20.Egr2.AllCell [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.ALL.20.Egr2.AllCell mm9 TFs and others Egr2 All cell types SRX270570,SRX270569,...SRX329255,SRX110637,SRX110636,SRX329257,SRX329256,SRX122432,SRX122435,SRX122433,SRX122434 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.ALL.20.Egr2.AllCell.bed ...

File list: Oth.ALL.10.Egr2.AllCell [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.ALL.10.Egr2.AllCell mm9 TFs and others Egr2 All cell types SRX270570,SRX270569,...SRX110637,SRX329255,SRX110636,SRX329257,SRX329256,SRX122434,SRX122432,SRX122435,SRX122433 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.ALL.10.Egr2.AllCell.bed ...

Egr3 dependent sympathetic target tissue innervation in the absence of neuron death.

Directory of Open Access Journals (Sweden)

Lin Li

Full Text Available Nerve Growth Factor (NGF is a target tissue derived neurotrophin required for normal sympathetic neuron survival and target tissue innervation. NGF signaling regulates gene expression in sympathetic neurons, which in turn mediates critical aspects of neuron survival, axon extension and terminal axon branching during sympathetic nervous system (SNS development. Egr3 is a transcription factor regulated by NGF signaling in sympathetic neurons that is essential for normal SNS development. Germline Egr3-deficient mice have physiologic dysautonomia characterized by apoptotic sympathetic neuron death and abnormal innervation to many target tissues. The extent to which sympathetic innervation abnormalities in the absence of Egr3 is caused by altered innervation or by neuron death during development is unknown. Using Bax-deficient mice to abrogate apoptotic sympathetic neuron death in vivo, we show that Egr3 has an essential role in target tissue innervation in the absence of neuron death. Sympathetic target tissue innervation is abnormal in many target tissues in the absence of neuron death, and like NGF, Egr3 also appears to effect target tissue innervation heterogeneously. In some tissues, such as heart, spleen, bowel, kidney, pineal gland and the eye, Egr3 is essential for normal innervation, whereas in other tissues such as lung, stomach, pancreas and liver, Egr3 appears to have little role in innervation. Moreover, in salivary glands and heart, two tissues where Egr3 has an essential role in sympathetic innervation, NGF and NT-3 are expressed normally in the absence of Egr3 indicating that abnormal target tissue innervation is not due to deregulation of these neurotrophins in target tissues. Taken together, these results clearly demonstrate a role for Egr3 in mediating sympathetic target tissue innervation that is independent of neuron survival or neurotrophin deregulation.

Computation and Analysis of EGR Mixing in Internal Combustion Engine Manifolds

OpenAIRE

Sakowitz, Alexander

2013-01-01

This thesis deals with turbulent mixing processes occurring in internal combustion engines, when applying exhaust gas recirculation (EGR). EGR is a very efficient way to reduce emissions of nitrogen oxides (NOx) in internal combustion engines. Exhaust gases are recirculated and mixed with the fresh intake air, reducing the oxygen con- centration of the combustion gas and thus the peak combustion temperatures. This temperature decrease results in a reduction of NOx emissions. When applying EGR...

Construction and identification of double-gene co-expression vector with radiation-inducible human TRAIL and endostatin

International Nuclear Information System (INIS)

Li Yanbo; Guo Caixia; Gong Pingsheng; Liu Yang; Liangshuo; Wang Hongfang; Wang Jianfeng; Gong Shouliang

2010-01-01

Objective: To construct a recombinant plasmid pshuttle-Egr1-shTRAIL-shES containing tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and endostatin double genes. Methods: The secretary endostatin gene (shES) fragment was amplified from the pMD19T-endostatin vector by PCR. The shES gene was ligated to pMD19Tand sequenced. Finally, using the gene recombinant technique, the recombinant plasmid pshuttle-Egr1- shTRAIL-shES with radiation-inducible Egr1 promoter, secretary TRAIL and endostatin double-gene was constructed. Results: The sequence of the shES gene was in concordance with that anticipated indicating shES gene was acquired successfully.Moreover, the results acquired by PCR and restrictive digestion identification of the recombinant plasmid pshuttle-Egr1-shTRAIL-shES and all the vectors refered to its construction confirmed that pshuttle-Egr1-shTRAIL-shES was constructed correctly. Conclusion: The radiation-inducible double-gene co-expression vector pshuttle-Egr1-shTRAIL-shES is constructed successfully, which would set the experimental foundation for further study on the anti-tumor effect of TRAIL and endostatin double-gene-radiotherapy and its related mechanisms. (authors)

Thermodynamic analysis of EGR effects on the first and second law efficiencies of a boosted spark-ignited direct-injection gasoline engine

International Nuclear Information System (INIS)

Li, Tie; Wu, Da; Xu, Min

2013-01-01

Highlights: • We clarified the mechanism of EGR improving fuel economy of gasoline engines. • At constant air–fuel ratio, reduction of heat transfer loss is most significant. • At full load, elimination of fuel enrichment is dominant. • Combustion irreversibility increases with EGR. • Availability in the exhaust and heat transfer losses is smaller than energy losses. - Abstract: Exhaust gas recirculation (EGR) is effective to improve fuel economy of spark-ignition gasoline engines, but the detailed mechanism needs to be further investigated. In this paper, an in-depth analysis of the effects of cooled EGR on the fuel conversion efficiency of a boosted, spark-ignited, direct-injection, gasoline engines operated at the full, medium and low loads is conducted with the engine experiment and 1-D cycle simulation based on the first and second laws of thermodynamics. For all the operating loads, EGR increases the ratio of specific heat of working gas, reduces the fraction of heat transfer through the combustion chamber walls, and improves the pumping work during the gas exchanging stroke. Besides, EGR may replace the fuel enrichment at high load, advance the combustion phasing and increase the degree of constant volume heat release at the medium and high loads. As a result, about 1.1–4.1% improvements in the brake thermal efficiency are obtained by the 12–17% EGR at different loads. Despite the increased fraction of combustion-generated irreversibility (destruction in availability or exergy), the fraction of indicated work in the total availability increases with EGR for all the operating loads. Among the influencing factors, the effect of reduction in the heat transfer loss owing to EGR is dominant in improvement of the fuel conversion efficiency at constant air–fuel ratio, while replacement of the fuel enrichment with EGR is most effective at full load

Prolactin and cortisol levels in women with endometriosis

Directory of Open Access Journals (Sweden)

A.P. Lima

2006-08-01

Full Text Available Endometriosis is a progressive estrogen-dependent disease affecting women during their reproductive years. The objective of the present study was to investigate whether endometriosis is associated with stress parameters. We determined cortisol and prolactin levels in serum, peritoneal and follicular fluid from infertile women with endometriosis and fertile women without the disease. The extent of the disease was staged according to the revised American Fertility Society classification (1997. Serum and peritoneal fluid were collected from 49 women aged 19 to 39 years undergoing laparoscopy. Eighteen women had stage I-II endometriosis and 10 had stage III-IV. Controls were 21 women undergoing laparoscopy for tubal sterilization. Follicular fluid was obtained from 39 women aged 25-39 years undergoing in vitro fertilization (21 infertile women with endometriosis and 18 infertile women without endometriosis. Serum prolactin levels were significantly higher in infertile women with stage III-IV endometriosis (28.9 ± 2.1 ng/mL than in healthy controls (13.2 ± 2.1 ng/mL. Serum cortisol levels were significantly higher in infertile women with stage III-IV endometriosis (20.1 ± 1.3 ng/mL than in controls (10.5 ± 1.4 ng/mL. Cortisol and prolactin levels in follicular fluid and peritoneal fluid did not differ significantly between groups. The high levels of cortisol and prolactin in the serum from women with endometriosis might contribute to the subfertility frequently associated with the disease. Moreover, since higher levels of cortisol and prolactin are often associated with stress, it is probable that stress might contribute to the development of endometriosis and its progression to advanced stages of the disease.

Effect of external hot EGR dilution on combustion, performance and particulate emissions of a GDI engine

International Nuclear Information System (INIS)

Xie, Fangxi; Hong, Wei; Su, Yan; Zhang, Miaomiao; Jiang, Beiping

2017-01-01

Highlights: • Effect of hot EGR on combustion and PN emission is investigated on a GDI engine. • Appropriate addition of hot EGR can reduce fuel consumption, NO_x and PN emission. • Relationship between BSFC and emissions of hot EGR is better than cooled EGR. • Condition with low-medium speeds and medium loads are more suitable for hot EGR. - Abstract: In this paper, an experimental investigation about the influence of hot EGR addition on the engine combustion, performance and particulate number emission was conducted at a spark-ignition gasoline direct injection (GDI) engine. Meanwhile, the different effects between cooled and hot EGR addition methods were compared and the variations of fuel consumption and particle number emissions under six engine operating conditions with different speeds and loads were analyzed. The research result indicated that increasing hot EGR ratio properly with adjustment of ignition timing could effectively improve the relationship among brake-specific fuel consumption (BSFC), NO_x and particle number emissions. When hot EGR ratio increased to 20%, not only BSFC but also the NO_x and particle number emissions were reduced, which were about 7%, 87% and 36% respectively. Compared with cooled EGR, the flame development and propagation speeds were accelerated, and cycle-by-cycle combustion variation decreased with hot EGR. Meanwhile, using hot EGR made the engine realize a better relationship among fuel consumption, NO_x and particle number emissions. The biggest improvements of BSFC, NO_x and particle number emissions were obtained at low-medium speed and medium load engine conditions by hot EGR addition method. While engine speed increased and load decreased, the improvement of engine fuel consumption and emission reduced with hot EGR method.

A predictive model for knock onset in spark-ignition engines with cooled EGR

International Nuclear Information System (INIS)

Chen, Longhua; Li, Tie; Yin, Tao; Zheng, Bin

2014-01-01

Highlights: • Ratio of specific heats should be used as variable in development of knock model. • Increases in EGR or excess air ratio lead to increases in the ratio of specific heats. • The widely-used Douaud–Eyzat correlation fails to predict the knock onset when increasing EGR. • The newly developed model including p, T, EGR and λ as variables predicts the knock onset accurately. • Effect of temperature at intake valve closure on the predicted knock onset is relatively small. - Abstract: A predictive knock model is crucial for one dimensional (1-D) engine cycle simulation that has been proven to be a powerful tool in both optimization of the conceptual design and reduction of calibration efforts in development of spark-ignition (SI) engines. With application of advanced technologies such as exhaust gas recirculation (EGR) in modern SI engines, update of knock model is needed to give an acceptable prediction of knock onset. In this study, bench tests of a turbocharged gasoline SI engine with cooled EGR system operated under knocking conditions were conducted, the cylinder pressure traces were analyzed by the band-pass filtering technique, and the crank angle of knock onset was determined by the signal energy ratio (SER) and image processing method. A knock model considering multi-variable effects including pressure, temperature, EGR ratio and excess air ratio (λ) is formulated and calibrated with the experimental data using the multi-island genetic algorithm (GA). The calculation method of the end gas temperature, the impacts of the ratio of specific heats as well as the temperature at the intake valve closure on the end gas temperature are discussed. The performance of the new model is compared with the widely-used phenomenological knock models such as Douaud–Eyzat model and Hoepke model. While the widely-used knock models fail to give acceptable predictions when increasing EGR with fuel enrichment operations, the new model predicts the knock

Combined Effect of food deprivation and serotonin injection on plasma prolactin and glucose levels in irradiated rats

International Nuclear Information System (INIS)

Girgis, R.B.; Abdel-Fattah, K.I.; Khamis, F.I.; Abu Zaid, N.M.

2004-01-01

The present study aims to investigate the role of serotonin (5-HT) on the homeostasis of plasma prolactin and glucose in rats induced by gamma irradiation and food deprivation. Animals were divided into seven groups; control, irradiated at a dose level of 6 Gy, injected with 500 mg/kg b.wt. 5-HT intra-peritoneally, injected with 5-HT before irradiation food deprived for 48 hrs then irradiated, food deprived then injected with 5-HT, and food deprived then injected with 5-HT before whole body irradiation. Samples were collected at 1,3, 7 and 14 days post irradiation. The results showed that gamma irradiation firstly elevated prolactin (PRL) levels in plasma (1 and 3 days) then the levels decreased after 7 and 14 days as compared to control values. Rats received serotonin before irradiation exhibited an increased level of PRL after 14 days post irradiation compared to control value, while the level decreased after 1, 3, 7 days post irradiation. Food deprivation for 48 hrs altered the effect of serotonin and /or irradiation on PRL levels in plasma. Rats injected with serotonin showed a decreased level of plasma prolactin in food deprived rats, 3 days post injection. The obtained results showed that serotonin causes variable effects on plasma prolactin compared to control values. Glucose plasma levels were increased in both irradiated and serotonin injected rats before irradiation, and also in serotonin injected rats as compared to control values. Irradiation of rats after 48 hrs food deprivation induced an increase in plasma glucose levels measured throughout the different experimental periods. Injection of serotonin to rats after 48 hrs food deprivation before irradiation increased plasma glucose levels after 1, 3, 7 and 14 days compared to control value. Also, injection of serotonin to 48 hrs food deprived rats increased glucose levels during all examined days of experiment.It could be concluded that serotonin may have a variable mechanism controlling prolactin

Energy efficiency impact of EGR on organizing clean combustion in diesel engines

International Nuclear Information System (INIS)

Divekar, Prasad S.; Chen, Xiang; Tjong, Jimi; Zheng, Ming

2016-01-01

Highlights: • Studied EGR impact on efficiency and emissions of diesel and dual-fuel combustion. • Quantified effectiveness of intake dilution for NOx reduction using EGR. • Identified suitable EGR ranges for mitigating emissions–efficiency trade-off. • Developed careful control of intake dilution and in-cylinder excess ratio. • Enabled ultra-low NOx in both diesel and dual-fuel combustion via EGR control. - Abstract: Exhaust gas recirculation (EGR) is a commonly recognized primary technique for reducing NOx emissions in IC engines. However, depending on the extent of its use, the application of EGR in diesel engines is associated with an increase in smoke emissions and a reduction in thermal efficiency. In this work, empirical investigations and parametric analyses are carried out to assess the impact of EGR in attaining ultra-low NOx emissions while minimizing the smoke and efficiency penalties. Two fuelling strategies are studied, namely diesel-only injection and dual-fuel injection. In the dual-fuel strategy, a high volatility liquid fuel is injected into the intake ports, and a diesel fuel is injected directly into the cylinder. The results suggest that the reduction in NOx can be directly correlated with the intake dilution caused by EGR and the correlation is largely independent of the fuelling strategy, the intake boost, and the engine load level. Simultaneously ultra-low NOx and smoke emissions can be achieved at high intake boost and intake dilution levels in the diesel-only combustion strategy and at high ethanol fractions in the dual-fuel strategy. The efficiency penalty associated with EGR is attributed to two primary factors; the combustion off-phasing and the reduction in combustion efficiency. The combustion off-phasing can be minimized by the closed loop control of the diesel injection timing in both the fuelling strategies, whereas the combustion efficiency can be improved by limiting the intake dilution to moderate levels. The

Cyclophilin B as a co-regulator of prolactin-induced gene expression and function in breast cancer cells

OpenAIRE

Fang, Feng; Zheng, Jiamao; Galbaugh, Traci L; Fiorillo, Alyson A; Hjort, Elizabeth E; Zeng, Xianke; Clevenger, Charles V

2010-01-01

The effects of prolactin (PRL) during the pathogenesis of breast cancer are mediated in part though Stat5 activity enhanced by its interaction with its transcriptional inducer, the prolyl isomerase cyclophilin B (CypB). We have demonstrated that knockdown of CypB decreases cell growth, proliferation, and migration, and CypB expression is associated with malignant progression of breast cancer. In this study, we examined the effect of CypB knockdown on PRL signaling in breast cancer cells. CypB...

Cloning of cDNA for a prolactin-inducible protein (PIP) and studies on the hormonal control of PIP gene expression in T47D human breast cancer cells

International Nuclear Information System (INIS)

Murphy, L.; Myal, Y.; Tsuyuki, D.; Shiu, R.

1986-01-01

Recently in this laboratory it was shown that in the human breast cancer cell line T47D, human prolactin of human growth hormone in the presence of hydrocortisone induced the synthesis and secretion of PIP's, a family of proteins which differed only in their degree of glycosylation. This finding represented the first demonstration of an inductin of specific proteins by prolactin in human target cells and has provided us with a unique model in which to study the molecular mechanism of multihormonal actions as well as the possible significance of prolactin in human breast cancer. In order to facilitate their studies the authors cloned PIP cDNA. The strategy chosen and the methods used are described in this article

Experimental investigation of particle emissions under different EGR ratios on a diesel engine fueled by blends of diesel/gasoline/n-butanol

International Nuclear Information System (INIS)

Huang, Haozhong; Liu, Qingsheng; Wang, Qingxin; Zhou, Chengzhong; Mo, Chunlan; Wang, Xueqiang

2016-01-01

Highlights: • The effects of EGR and blend fuels on particulate emission were studied in CI engine. • EGR ⩽ 20%, gasoline or n-butanol increases total particulate number concentration. • EGR ⩾ 30%, gasoline or n-butanol reduces total particulate number concentration. • As EGR ratio increased, the particulate mass concentrations of four fuels increased. • Gasoline or n-butanol increases the ratio of sub-25 nm particles number concentration. - Abstract: The particle emission characteristics of a high-pressure common-rail engine under different EGR conditions were investigated, using pure diesel (D100), diesel/gasoline (with a volume ratio of 70:30, D70G30), diesel/n-butanol (with a volume ratio of 70:30, D70B30) and diesel/gasoline/n-butanol (with a volume ratio of 70:15:15, D70G15B15) for combustion. Our results show that, with increasing EGR ratios, the in-cylinder pressure peak decreases and the heat release is delayed for the combustion of each fuel. At an EGR ratio of 30%, the combustion pressure peaks of D70G30, D70B30, D70G15B15 and D100 have similar values; with an EGR ratio of 40%, the combustion pressure peaks and release rate peaks of D70G30 and D70G15B15 are both lower with respect to D100. For small and medium EGR ratios (⩽20%), after the addition of gasoline and/or n-butanol to the fuel, the total particle number concentration (TPNC) increases, while both the soot emissions and the average geometric size of particles decrease. At large EGR ratios (30% and 40%), the TPNC of D70B30, D70G15B15 and D70G20 compared to D100 are reduced by a maximum amount of 74.7%, 66.7% and 28.6%, respectively. As the EGR ratio increases, the total particle mass concentration increases gradually for all four fuels. Blending gasoline or/and n-butanol into diesel induces an increase in the number concentration of sub-25 nm particles (PN25) which may be harmful in terms of health. However, the PN25 decreases with increasing the EGR ratio for all the tested fuels

The HMGA1 Pseudogene 7 Induces miR-483 and miR-675 Upregulation by Activating Egr1 through a ceRNA Mechanism

Directory of Open Access Journals (Sweden)

Marco De Martino

2017-11-01

Full Text Available Several studies have established that pseudogene mRNAs can work as competing endogenous RNAs and, when deregulated, play a key role in the onset of human neoplasias. Recently, we have isolated two HMGA1 pseudogenes, HMGA1P6 and HMGA1P7. These pseudogenes have a critical role in cancer progression, acting as micro RNA (miRNA sponges for HMGA1 and other cancer-related genes. HMGA1 pseudogenes were found overexpressed in several human carcinomas, and their expression levels positively correlate with an advanced cancer stage and a poor prognosis. In order to investigate the molecular alterations following HMGA1 pseudogene 7 overexpression, we carried out miRNA sequencing analysis on HMGA1P7 overexpressing mouse embryonic fibroblasts. Intriguingly, the most upregulated miRNAs were miR-483 and miR-675 that have been described as key regulators in cancer progression. Here, we report that HMGA1P7 upregulates miR-483 and miR-675 through a competing endogenous RNA mechanism with Egr1, a transcriptional factor that positively regulates miR-483 and miR-675 expression.

Activation of protein kinase C inhibits synthesis and release of decidual prolactin

International Nuclear Information System (INIS)

Harman, I.; Costello, A.; Ganong, B.; Bell, R.M.; Handwerger, S.

1986-01-01

Activation of calcium-activated, phospholipid-dependent protein kinase C by diacylglycerol and phorbol esters has been shown to mediate release of hormones in many systems. To determine whether protein kinase C activation is also involved in the regulation of prolactin release from human decidual, the authors have examined the effects of various acylglycerols and phorbol esters on the synthesis and release of prolactin from cultured human decidual cells. sn-1,2-Dioctanolyglycerol (diC 8 ), which is known to stimulate protein kinase C in other systems, inhibited prolactin release in a dose-dependent manner with maximal inhibition of 53.1% at 100 μM. Diolein (100 μM), which also stimulates protein kinase C activity in some systems, inhibited prolactin release by 21.3%. Phorbol 12-myristate 13-acetate (PMA), phorbol 12,13-didecanoate, and 4β-phorbol 12,13-dibutyrate, which activate protein kinase C in other systems, also inhibited the release of prolactin, which the protein kinase C inactivate 4α-phorbol-12,13-didecanoate was without effect. The inhibition of prolactin release was secondary to a decrease in prolactin synthesis. Although diC 8 and PMA inhibited the synthesis and release of prolactin, these agents had no effect on the synthesis or release of trichloroacetic acid-precipitable [ 35 S]methionine-labeled decidual proteins and did not cause the release of the cytosolic enzymes lactic dehydrogenase and alkaline phosphatase. DiC 8 and PMA stimulates the specific activity of protein kinase C in decidual tissue by 14.6 and 14.0-fold, respectively. The inhibition of the synthesis and release of prolactin by diC 8 and phorbol esters strongly implicates protein kinase C in the regulation of the production and release of prolactin from the decidua

Influence of ethanol and EGR on laminar burning behaviors of FACE-C gasoline and its surrogate

KAUST Repository

Mannaa, Ossama Abde El Hamid; Mansour, Morkous; Roberts, William L.; Chung, Suk-Ho

2017-01-01

Laminar burning velocities of FACE-C gasoline and a surrogate comprised of toluene primary reference fuels (TPRFs) were investigated under the effects of EGR dilution and ethanol blending. Measurements were conducted in a spherical constant volume combustion chamber for a range of equivalence ratios from 0.8 to 1.6 at initial temperatures and pressures up to 383 K and 0.6 MPa, respectively. These measurements highlighted the effects of real combustion residuals at mole fractions up to 0.3 and various volumetric percentages of ethanol blending. For both studied fuels, significant reductions in stretched and un-stretched flame speeds were observed for mixtures laden with real combustion residuals. Blends with less than 50% ethanol showed a minimal enhancement in the flame speed. By combining both EGR and ethanol blending, the flame speed reduction by EGR can be compensated for with ethanol addition. For example, up to 10% of EGR requires 60% ethanol blending to maintain the same flame speed. Flame stability enhancement by EGR addition was also quantified through the determination of the Markstein length.

Influence of ethanol and EGR on laminar burning behaviors of FACE-C gasoline and its surrogate

KAUST Repository

Mannaa, Ossama Abde El Hamid

2017-10-31

Laminar burning velocities of FACE-C gasoline and a surrogate comprised of toluene primary reference fuels (TPRFs) were investigated under the effects of EGR dilution and ethanol blending. Measurements were conducted in a spherical constant volume combustion chamber for a range of equivalence ratios from 0.8 to 1.6 at initial temperatures and pressures up to 383 K and 0.6 MPa, respectively. These measurements highlighted the effects of real combustion residuals at mole fractions up to 0.3 and various volumetric percentages of ethanol blending. For both studied fuels, significant reductions in stretched and un-stretched flame speeds were observed for mixtures laden with real combustion residuals. Blends with less than 50% ethanol showed a minimal enhancement in the flame speed. By combining both EGR and ethanol blending, the flame speed reduction by EGR can be compensated for with ethanol addition. For example, up to 10% of EGR requires 60% ethanol blending to maintain the same flame speed. Flame stability enhancement by EGR addition was also quantified through the determination of the Markstein length.

Plasma concentrations of prolactin in overtly pseudopregnant Afghan hounds and the effect of metergoline.

Science.gov (United States)

Okkens, A C; Dieleman, S J; Kooistra, H S; Bevers, M M

1997-01-01

The effect of metergoline, a 5-hydroxytryptamine (serotonin) antagonist, on the plasma concentrations of prolactin in overtly pseudopregnant Afghan hounds and on the clinical symptoms of overt pseudopregnancy were studied. Plasma concentrations of prolactin and progesterone were determined in six Afghan hounds with signs of overt pseudopregnancy for 2-3 weeks and in three Afghan hounds that were not pseudopregnant at the time of blood sampling. In the overtly pseudopregnant bitches the plasma concentrations of prolactin before treatment (35.5 +/- 8.5 micrograms l-1) were significantly higher than the plasma concentrations of prolactin of the three bitches that were not pseudopregnant (6.3 +/- 0.5 micrograms l-1); the latter values were similar to those of non-pseudopregnant beagle bitches during the total luteal phase. The six pseudopregnant Afghan hounds were treated for 10 days with the antiserotoninergic drug metergoline. At 2 h after the onset of treatment with metergoline, the mean plasma concentration of prolactin had decreased to 10.8 +/- 2.9 micrograms l-1. The plasma concentrations of prolactin continued to decline to 5.4 +/- 1.0 micrograms l-1 at 4 h and to 1.0 +/- 0.1 microgram l-1 during treatment days 3-10. Signs of pseudopregnancy, such as swelling of the mammary glands and digging, decreased during the treatment period. The treatment was associated with mild behavioural side effects such as whimpering and aggressiveness. These side effects are probably not related to suppression of prolactin but are due to a direct effect on serotoninergic pathways in the brain. It is concluded that high plasma concentrations of prolactin are associated with the development and maintenance of pseudopregnancy. The serotonin antagonist metergoline strongly suppresses plasma concentrations of prolactin in pseudopregnant dogs and decreases the clinical signs of pseudopregnancy.

Maintenance of prolactin receptors in human breast cancer

International Nuclear Information System (INIS)

Ben-David, M.; Dror, Y.; Biran, S.

1981-01-01

Breast tissue specimens of 110 women with various stages of breast cancer were tested in vitro to determine their specific binding sites for human prolactin. In contrast to the case of steroid receptors, binding sites for prolactin were found in the vast majority of breast cancer tissue. Distribution profiles giving amount of prolactin receptor and their affinity coefficients were found to be similar in the tissues of women whose ages, hormonal status, or stage of breast cancer varied. These findings show that in contrast to steroid receptors, human breast cancer tissue maintains binding sites for prolactin. The findings also indicate that there may be a higher dependency of breast cancer on prolactin than on steroids. Clinical trials must be carried out to determine the role of ''positive'' prolactin receptors in prognosis and prediction of response to future hormone therapy. (author)

A disposable electrochemical immunosensor for prolactin involving affinity reaction on streptavidin-functionalized magnetic particles

International Nuclear Information System (INIS)

Moreno-Guzman, Maria; Gonzalez-Cortes, Araceli; Yanez-Sedeno, Paloma; Pingarron, Jose M.

2011-01-01

A novel electrochemical immunosensor was developed for the determination of the hormone prolactin. The design involved the use of screen-printed carbon electrodes and streptavidin-functionalized magnetic particles. Biotinylated anti-prolactin antibodies were immobilized onto the functionalized magnetic particles and a sandwich-type immunoassay involving prolactin and anti-prolactin antibody labelled with alkaline phosphatase was employed. The resulting bio-conjugate was trapped on the surface of the screen-printed electrode with a small magnet and prolactin quantification was accomplished by differential pulse voltammetry of 1-naphtol formed in the enzyme reaction using 1-naphtyl phosphate as alkaline phosphatase substrate. All variables involved in the preparation of the immunosensor and in the electrochemical detection step were optimized. The calibration plot for prolactin exhibited a linear range between 10 and 2000 ng mL -1 with a slope value of 7.0 nA mL ng -1 . The limit of detection was 3.74 ng mL -1 . Furthermore, the modified magnetic beads-antiprolactin conjugates showed an excellent stability. The immunosensor exhibited also a high selectivity with respect to other hormones. The analytical usefulness of the immnunosensor was demonstrated by analyzing human sera spiked with prolactin at three different concentration levels.

A disposable electrochemical immunosensor for prolactin involving affinity reaction on streptavidin-functionalized magnetic particles

Energy Technology Data Exchange (ETDEWEB)

Moreno-Guzman, Maria; Gonzalez-Cortes, Araceli [Department of Analytical Chemistry, Faculty of Chemistry, University Computense of Madrid, 28040 Madrid (Spain); Yanez-Sedeno, Paloma, E-mail: yseo@quim.ucm.es [Department of Analytical Chemistry, Faculty of Chemistry, University Computense of Madrid, 28040 Madrid (Spain); Pingarron, Jose M. [Department of Analytical Chemistry, Faculty of Chemistry, University Computense of Madrid, 28040 Madrid (Spain)

2011-04-29

A novel electrochemical immunosensor was developed for the determination of the hormone prolactin. The design involved the use of screen-printed carbon electrodes and streptavidin-functionalized magnetic particles. Biotinylated anti-prolactin antibodies were immobilized onto the functionalized magnetic particles and a sandwich-type immunoassay involving prolactin and anti-prolactin antibody labelled with alkaline phosphatase was employed. The resulting bio-conjugate was trapped on the surface of the screen-printed electrode with a small magnet and prolactin quantification was accomplished by differential pulse voltammetry of 1-naphtol formed in the enzyme reaction using 1-naphtyl phosphate as alkaline phosphatase substrate. All variables involved in the preparation of the immunosensor and in the electrochemical detection step were optimized. The calibration plot for prolactin exhibited a linear range between 10 and 2000 ng mL{sup -1} with a slope value of 7.0 nA mL ng{sup -1}. The limit of detection was 3.74 ng mL{sup -1}. Furthermore, the modified magnetic beads-antiprolactin conjugates showed an excellent stability. The immunosensor exhibited also a high selectivity with respect to other hormones. The analytical usefulness of the immnunosensor was demonstrated by analyzing human sera spiked with prolactin at three different concentration levels.

Effect of exhaust gas recirculation (EGR) and multiple injections on diesel soot nano-structure and reactivity

International Nuclear Information System (INIS)

Rohani, Behzad; Bae, Choongsik

2017-01-01

Highlights: • EGR reduced the nano-structural order, regardless of injection strategy. • EGR reduces both VOF and reactivity, regardless of injection strategy. • Longer dwell time between pilot and main injection increases VOF and reactivity. • With EGR, VOF and reactivity are both reduced and un-affected by injection strategy. • VOF-reactivity correlation (without causality) suggests role of surface roughness. - Abstract: The physio-chemical characteristics of soot particles are of importance with regard to performance of diesel after-treatment systems. In this study, the soot particles generated in a single-cylinder heavy-duty diesel engine are examined in terms of nanostructure, oxidative reactivity and volatile organic fraction (VOF), using thermogravimetric analysis (TGA), X-ray diffraction (XRD), Raman micro-spectroscopy, and high resolution transmission electron microscopy (HRTEM). Five different injection strategies including single injection and multiple injections with various pilot injection amounts and dwell times were tested with and without exhaust gas recirculation (EGR), while combustion phasing, engine speed, and fuel injection quantity was matched for all cases. Results indicate that for the soot produced under EGR condition, nano-structural order (indicated by crystallite size obtained from XRD and AD1/AG resulted from the Raman Analysis) can explain the soot reactivity. However, in the absence of EGR, the reactivity trend cannot be explained by the structural order. It is discussed that a possible reason can be a higher level of in-cylinder oxidation in non-EGR cases (indicated by higher level of surface functional groups) which roughens the soot surface, and enhances the oxidation by increasing the specific soot surface area. It is also found that in the absence of EGR, different injection strategies impact the soot reactivity and VOF content, which can be explained mainly through the level of charge premixed-ness and the in

Crystal structure of a prolactin receptor antagonist bound to the extracellular domain of the prolactin receptor

DEFF Research Database (Denmark)

Svensson, L Anders; Bondensgaard, Kent; Nørskov-Lauritsen, Leif

2008-01-01

The crystal structure of the complex between an N-terminally truncated G129R human prolactin (PRL) variant and the extracellular domain of the human prolactin receptor (PRLR) was determined at 2.5A resolution by x-ray crystallography. This structure represents the first experimental structure...... studies, the structural data imply that the definition of PRL binding site 1 should be extended to include residues situated in the N-terminal part of loop 1 and in the C terminus. Comparison of the structure of the receptor-bound PRL variant with the structure reported for the unbound form of a similar...... scale rearrangements and structuring occur in the flexible N-terminal part of loop 1. Hydrogen exchange mass spectrometry data imply that the dynamics of the four-helix bundle in solution generally become stabilized upon receptor interaction at binding site 1....

Prolactin secretion: the impact of dynamic studies

International Nuclear Information System (INIS)

L'Hermite, M.; Degueldre, M.; Caufriez, A.; Delvoye, P.; Robyn, C.

1975-01-01

Human prolactin blood levels were determined by radioimmunoassay in basal condition and in response to various inhibiting and/or stimulating agents (levodopa, water overload, insulinic hypoglycaemia, synthetic TRH, sulpiride) in cases of disturbed hypothalamo-pituitary axis (failure to lactate, prolactin-secreting pituitary adenomas, acromegaly, other pituitary tumours, clinical panhypopituitarism). A blunted prolactin response to suckling was evidenced in 2 post-partum women who were unable to breast feed. Hyperprolactinaemia, whether related to the existence of a prolactin-producing adenoma or not was associated with the disappearance of the normal circadian pattern of prolactin secretion and with a blunted relative response to TRH; the latter phenomenon occurred also in acromegaly regardless of the basal prolactinaemia, and during the last trimester of pregnancy. Water overload was unsuccessful to suppress prolactin during the last trimester of pregnancy while the acute administration of levodopa was quite effective in about half of the patients with pituitary tumour. Therefore none of the dynamic tests presently studied allowed to attribute a hyperprolactinaemia to a pituitary tumour rather than to a functional disturbance. On the contrary, stimulation tests can help to locate the level of a defect in cases of hypopituitarism [fr

Association of Thyroid Profile and Prolactin Level in Patient with Secondary Amenorrhea

Science.gov (United States)

Shrestha, Sujata; Neupane, Sunita; Gautam, Narayan; Dubey, Raju Kumar; Jha, Amit Chandra; Doshi, Nilesh Raj; Jayan, Archana

2016-01-01

Background Amenorrhea is the absence of menstrual periods. It has multiple social consequences as it may leads to infertility. This case control study was conducted for determining the association of thyroid hormones with hyperprolactinemia in patient with amenorrhea. Methods We investigated 50 women with diagnosed cases of secondary amenorrhoea, who attended UCMS hospital, for hormonal evaluations. Fifty two healthy women were taken as the controls. The thyroid dysfunction and serum prolactin level were reviewed in cases and in the controls. Results Mean serum prolactin level was found to be significantly higher in the cases as compared to the controls. Mean serum fT3 and fT4 level in the hyperprolactinemic cases (mean = 2.67, SD = 1.04 pg/ml) and (mean = 1.38, SD = 0.51 ng/dl respectively) were slightly lower as compared to normoprolactinemic cases (mean = 3.21, SD = 1.86 pg/ml) and (mean = 1.73, SD = 1.37 ng/dl) respectively. Mean TSH of normoprolactinemic and hyperprolactinemic cases were comparable (P = 0.049). There was positive correlation between prolactin, BMI and TSH whereas negative correlation of prolactin was seen with fT3, fT4 and age. In hyperprolactainemic cases, prolactin was found to be negatively correlated with TSH (r = −0.155, P = 0.491) whereas prolactin was positively correlated with TSH (r = 0.296, P = 0.126) in normoprolactainemic cases. Conclusions Thus, hyperprolactinemia with thyroid dysfunction may be contributory hormonal factor in patient with amenorrhoea and as such, estimation of prolactin, fT3, fT4 and TSH should be included for diagnostic evaluation of amenorrhea. PMID:27904425

Prolactin prevents acute stress-induced hypocalcemia and ulcerogenesis by acting in the brain of rat.

Science.gov (United States)

Fujikawa, Takahiko; Soya, Hideaki; Tamashiro, Kellie L K; Sakai, Randall R; McEwen, Bruce S; Nakai, Naoya; Ogata, Masato; Suzuki, Ikukatsu; Nakashima, Kunio

2004-04-01

Stress causes hypocalcemia and ulcerogenesis in rats. In rats under stressful conditions, a rapid and transient increase in circulating prolactin (PRL) is observed, and this enhanced PRL induces PRL receptors (PRLR) in the choroid plexus of rat brain. In this study we used restraint stress in water to elucidate the mechanism by which PRLR in the rat brain mediate the protective effect of PRL against stress-induced hypocalcemia and ulcerogenesis. We show that rat PRL acts through the long form of PRLR in the hypothalamus. This is followed by an increase in the long form of PRLR mRNA expression in the choroid plexus of the brain, which provides protection against restraint stress in water-induced hypocalcemia and gastric erosions. We also show that PRL induces the expression of PRLR protein and corticotropin-releasing factor mRNA in the paraventricular nucleus. These results suggest that the PRL levels increase in response to stress, and it moves from the circulation to the cerebrospinal fluid to act on the central nervous system and thereby plays an important role in helping to protect against acute stress-induced hypocalcemia and gastric erosions.

α-Estrogen and Progesterone Receptors Modulate Kisspeptin Effects on Prolactin: Role in Estradiol-Induced Prolactin Surge in Female Rats.

Science.gov (United States)

Aquino, Nayara S S; Araujo-Lopes, Roberta; Henriques, Patricia C; Lopes, Felipe E F; Gusmao, Daniela O; Coimbra, Candido C; Franci, Celso R; Reis, Adelina M; Szawka, Raphael E

2017-06-01

Kisspeptin (Kp) regulates prolactin (PRL) in an estradiol-dependent manner. We investigated the interaction between ovarian steroid receptors and Kp in the control of PRL secretion. Intracerebroventricular injections of Kp-10 or Kp-234 were performed in ovariectomized (OVX) rats under different hormonal treatments. Kp-10 increased PRL release and decreased 3,4-dihydroxyphenylacetic acid levels in the median eminence (ME) of OVX rats treated with estradiol (OVX+E), which was prevented by tamoxifen. Whereas these effects of Kp-10 were absent in OVX rats, they were replicated in OVX rats treated with selective agonist of estrogen receptor (ER)α, propylpyrazole triol, but not of ERβ, diarylpropionitrile. Furthermore, the Kp-10-induced increase in PRL was two times higher in OVX+E rats also treated with progesterone (OVX+EP), which was associated with a reduced expression of both tyrosine hydroxylase (TH) and Ser40-phosphorylated TH in the ME. Kp-10 also reduced dopamine levels in the ME of OVX+EP rats, an effect blocked by the progesterone receptor (PR) antagonist RU486. We also determined the effect of Kp antagonism with Kp-234 on the estradiol-induced surges of PRL and luteinizing hormone (LH), using tail-tip blood sampling combined with ultrasensitive enzyme-linked immunosorbent assay. Kp-234 impaired the early phase of the PRL surge and prevented the LH surge in OVX+E rats. Thus, we provide evidence that Kp stimulation of PRL release requires ERα and is potentiated by progesterone via PR activation. Moreover, alongside its essential role in the LH surge, Kp seems to play a role in the peak phase of the estradiol-induced PRL surge. Copyright © 2017 Endocrine Society.

Growth hormone and prolactin radioimmunoassay in early diagnosis of pituitary tumors

International Nuclear Information System (INIS)

Gembicki, M.; Kosowicz, J.

1978-01-01

Results of prolactin and HGH determination in basal conditions and following stimulation tests in the group of 68 patients with pituitary or suprasellar tumors are presented. In acromegaly elevated level of HGH in fasting state, lack of supression after glucose loading and parodoxical drop of HGH after L-dopa administration were observed. In pituitary tumors without acromegaly determinations of HGH during insulin induced hypoglycemia revealed lack of HGH response to such stimulation in 25 cases which indicated hypopituitarism. In 10 cases elevated prolactin levels (48 - 1000 ng/ml) were observed, this indicates that some of so-called inactive tumors are in fact hormonally active. (author)

Fast spatially resolved exhaust gas recirculation (EGR) distribution measurements in an internal combustion engine using absorption spectroscopy.

Science.gov (United States)

Yoo, Jihyung; Prikhodko, Vitaly; Parks, James E; Perfetto, Anthony; Geckler, Sam; Partridge, William P

2015-09-01

Exhaust gas recirculation (EGR) in internal combustion engines is an effective method of reducing NOx emissions while improving efficiency. However, insufficient mixing between fresh air and exhaust gas can lead to cycle-to-cycle and cylinder-to-cylinder non-uniform charge gas mixtures of a multi-cylinder engine, which can in turn reduce engine performance and efficiency. A sensor packaged into a compact probe was designed, built and applied to measure spatiotemporal EGR distributions in the intake manifold of an operating engine. The probe promotes the development of more efficient and higher-performance engines by resolving high-speed in situ CO2 concentration at various locations in the intake manifold. The study employed mid-infrared light sources tuned to an absorption band of CO2 near 4.3 μm, an industry standard species for determining EGR fraction. The calibrated probe was used to map spatial EGR distributions in an intake manifold with high accuracy and monitor cycle-resolved cylinder-specific EGR fluctuations at a rate of up to 1 kHz.

Cycle-by-cycle variations in a spark ignition engine fueled with natural gas-hydrogen blends combined with EGR

Energy Technology Data Exchange (ETDEWEB)

Huang, Bin; Hu, Erjiang; Huang, Zuohua; Zheng, Jianjun; Liu, Bing; Jiang, Deming [State Key Laboratory of Multiphase Flow in Power Engineering, Xi' an Jiaotong University, 710049 Xi' an (China)

2009-10-15

Study of cycle-by-cycle variations in a spark ignition engine fueled with natural gas-hydrogen blends combined with exhaust gas recirculation (EGR) was conducted. The effects of EGR ratio and hydrogen fraction on engine cycle-by-cycle variations are analyzed. The results show that the cylinder peak pressure, the maximum rate of pressure rise and the indicated mean effective pressure decrease and cycle-by-cycle variations increase with the increase of EGR ratio. Interdependency between the above parameters and their corresponding crank angles of cylinder peak pressure is decreased with the increase of EGR ratio. For a given EGR ratio, combustion stability is promoted and cycle-by-cycle variations are decreased with the increase of hydrogen fraction in the fuel blends. Non-linear relationship is presented between the indicated mean effective pressure and EGR ratio. Slight influence of EGR ratio on indicated mean effective pressure is observed at low EGR ratios while large influence of EGR ratio on indicated mean effective pressure is demonstrated at high EGR ratios. The high test engine speed has lower cycle-by-cycle variations due to the enhancement of air flow turbulence and swirls in the cylinder. Increasing hydrogen fraction can maintain low cycle-by-cycle variations at high EGR ratios. (author)

Genetic evidence for the association between the early growth response 3 (EGR3 gene and schizophrenia.

Directory of Open Access Journals (Sweden)

Rui Zhang

Full Text Available Recently, two genome scan meta-analysis studies have found strong evidence for the association of loci on chromosome 8p with schizophrenia. The early growth response 3 (EGR3 gene located in chromosome 8p21.3 was also found to be involved in the etiology of schizophrenia. However, subsequent studies failed to replicate this finding. To investigate the genetic role of EGR3 in Chinese patients, we genotyped four SNPs (average interval ∼2.3 kb in the chromosome region of EGR3 in 470 Chinese schizophrenia patients and 480 healthy control subjects. The SNP rs35201266 (located in intron 1 of EGR3 showed significant differences between cases and controls in both genotype frequency distribution (P = 0.016 and allele frequency distribution (P = 0.009. Analysis of the haplotype rs35201266-rs3750192 provided significant evidence for association with schizophrenia (P = 0.0012; a significant difference was found for the common haplotype AG (P = 0.0005. Furthermore, significant associations were also found in several other two-, and three-SNP tests of haplotype analyses. The meta-analysis revealed a statistically significant association between rs35201266 and schizophrenia (P = 0.0001. In summary, our study supports the association of EGR3 with schizophrenia in our Han Chinese sample, and further functional exploration of the EGR3 gene will contribute to the molecular basis for the complex network underlying schizophrenia pathogenesis.

Effect of LH and prolactin on steroid secretion by perifused luteal tissue from pregnant gilts with induced hypoprolactinemia or after passive immunoneutralization of LH

International Nuclear Information System (INIS)

Szafranska, B.; Przala, J.; Grazul-Bilska, A.

1992-01-01

The study was performed using luteal tissue obtained from 24 pregnant gilts. Group 1 was treated with bromocriptine (BR) from 37th to 42nd day of day of pregnancy. Group 2 was treated with homologous anti-pLH serum from 37th to 42nd day of pregnancy. Group 3 was given BR from 67th to 72nd day of gestation. Group 4 received anti-pLH serum from 67th to 72nd day of pregnancy. The effect of exogenous LH or prolactin (100 ng/ml) on secretion of progesterone (P 4 ) and estradiol (E 2 ) by luteal tissue was studied using perfusion technique. Prolactin caused a significant (P 4 secretion by luteal tissue from gilts in groups 1 and 4. Both LH and prolactin decreased (P 4 and E 2 secretion by luteal tissue from gilts from groups 4 and 2, respectively. The results demonstrate that both LH and prolactin have a regulatory role in steroid secretion by luteal tissue of gilts in the mid- and late period of pregnancy. (author). 28 refs, 2 figs

Induction of the early response protein EGR-1 in human tumour cells after ionizing radiation is correlated with a reduction of repair of lethal lesions and an increase of repair of sublethal lesions

NARCIS (Netherlands)

Franken, Nicolaas A. P.; ten Cate, Rosemarie; van Bree, Chris; Haveman, Jaap

2004-01-01

The role of EGR-1 in potentially lethal damage repair (PLDR) was studied. Induction of the early response protein EGR-1 and survival after ionizing radiation of two human tumour cell lines after culturing for 48 h in serum-deprived medium was investigated. The glioblastoma cell line (Gli-6) and a

Numerical Investigation on Effects of Assigned EGR Stratification on a Heavy Duty Diesel Engine with Two-Stage Fuel Injection

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Zhaojie Shen

2018-02-01

Full Text Available External exhaust gas recirculation (EGR stratification in diesel engines contributes to reduction of toxic emissions. Weak EGR stratification lies in that strong turbulence and mixing between EGR and intake air by current introduction strategies of EGR. For understanding of ideal EGR stratification combustion, EGR was assigned radically at −30 °CA after top dead center (ATDC to organize strong EGR stratification using computational fluid dynamics (CFD. The effects of assigned EGR stratification on diesel performance and emissions are discussed in this paper. Although nitric oxides (NOx and soot emissions are both reduced by means of EGR stratification compared to uniform EGR, the trade-off between NOx and soot still exists under the condition of arranged EGR stratification with different fuel injection strategies. A deterioration of soot emissions was observed when the interval between main and post fuel injection increased, while NO emissions increased first then reduced. The case with a 4 °CA interval between main and post fuel injection is suitable for acceptable NO and soot emissions. Starting the main fuel injection too early and too late is not acceptable, which results in high NO emissions and high soot emissions respectively. The start of the main fuel injection −10 °CA ATDC is suitable.

Development of radioimmunoassay for prolactin binding protein

Energy Technology Data Exchange (ETDEWEB)

Raikar, R.S.; Sheth, A.R. (Institute for Research in Reproduction, Bombay (India))

1982-01-01

Using a homogenous prolactin binding protein (PBP) preparations from rat seminal vesicle secretion, a sensitive and specific radioimmunoassay (RIA) for PBP has been developed. The assay was highly specific and showed no cross-reaction with other protein hormones from various species. The antiserum had an affinity constant (Ka) of 2.66 x 10/sup 10/ M/sup -1/. The assay sensitivity was in the range of 0.5-1.0 ng of pure PBP per assay tube and the intra- and inter-assay coefficients of variations were 6-8% and 12-14.5% respectively. The overall recovery of PBP to the rat seminal vesicle secretion was 96.8%. Using this RIA, PBP levels in various biological fluids and reproductive tissues were measured. Azoospermic human semen contained significantly higher levels of PBP than normospermic semen. The seminal vesicle of rat exhibited the highest concentration of PBP. Administration of antiserum to PBP to mature male rats resulted in a significant reduction in the weight of ventral prostrate and serum prolactin levels were significantly elevated in these animals suggesting that the antibody raised against the PBP was capable of blocking prolactin receptors.

A high pressure liquid chromatography method for separation of prolactin forms.

Science.gov (United States)

Bell, Damon A; Hoad, Kirsten; Leong, Lillian; Bakar, Juwaini Abu; Sheehan, Paul; Vasikaran, Samuel D

2012-05-01

Prolactin has multiple forms and macroprolactin, which is thought not to be bioavailable, can cause a raised serum prolactin concentration. Gel filtration chromatography (GFC) is currently the gold standard method for separating macroprolactin, but is labour-intensive. Polyethylene glycol (PEG) precipitation is suitable for routine use but may not always be accurate. We developed a high pressure liquid chromatography (HPLC) assay for macroprolactin measurement. Chromatography was carried out using an Agilent Zorbax GF-250 (9.4 × 250 mm, 4 μm) size exclusion column and 50 mmol/L Tris buffer with 0.15 mmol/L NaCl at pH 7.2 as mobile phase, with a flow rate of 1 mL/min. Serum or plasma was diluted 1:1 with mobile phase and filtered and 100 μL injected. Fractions of 155 μL were collected for prolactin measurement and elution profile plotted. The area under the curve of each prolactin peak was calculated to quantify each prolactin form, and compared with GFC. Clear separation of monomeric-, big- and macroprolactin forms was achieved. Quantification was comparable to GFC and precision was acceptable. Total time from injection to collection of the final fraction was 16 min. We have developed an HPLC method for quantification of macroprolactin, which is rapid and easy to perform and therefore can be used for routine measurement.

Effects of melatonin and prolactin in reproduction: review of literature.

Science.gov (United States)

Tenorio, Fernanda das Chagas Angelo Mendes; Simões, Manuel de Jesus; Teixeira, Valéria Wanderley; Teixeira, Álvaro Aguiar Coelho

2015-01-01

The pineal gland is responsible for producing a hormone called melatonin (MEL), and is accepted as the gland that regulates reproduction in mammals. Prolactin (PRL) also exhibits reproductive activity in animals in response to photoperiod. It is known that the concentrations of PRL are high in the summer and reduced during winter, the opposite of what is seen with melatonin in these seasons. In placental mammals, both prolactin and melatonin affect implantation, which is considered a critical point of pregnancy, since a successful pregnancy requires the development of a synchronous interaction between the endometrium and blastocyst for placental development. It is also known that PRL levels during pregnancy are essential for the maintenance of pregnancy, because this hormone induces the corpus luteum to produce progesterone, in addition to stimulating blastocyst implantation to maintain pregnancy and form the placenta. However, melatonin levels in plasma have also been shown to increase during pregnancy, peaking at the end of this period, which suggests that this hormone plays an important role in the maintenance of pregnancy. Thus, it is clear that treatment with prolactin or melatonin interferes with the processes responsible for the development and maintenance of pregnancy.

Effects of melatonin and prolactin in reproduction: review of literature

Directory of Open Access Journals (Sweden)

Fernanda das Chagas Angelo Mendes Tenorio

2015-06-01

Full Text Available Summary The pineal gland is responsible for producing a hormone called melatonin (MEL, and is accepted as the gland that regulates reproduction in mammals. Prolactin (PRL also exhibits reproductive activity in animals in response to photoperiod. It is known that the concentrations of PRL are high in the summer and reduced during winter, the opposite of what is seen with melatonin in these seasons. In placental mammals, both prolactin and melatonin affect implantation, which is considered a critical point of pregnancy, since a successful pregnancy requires the development of a synchronous interaction between the endometrium and blastocyst for placental development. It is also known that PRL levels during pregnancy are essential for the maintenance of pregnancy, because this hormone induces the corpus luteum to produce progesterone, in addition to stimulating blastocyst implantation to maintain pregnancy and form the placenta. However, melatonin levels in plasma have also been shown to increase during pregnancy, peaking at the end of this period, which suggests that this hormone plays an important role in the maintenance of pregnancy. Thus, it is clear that treatment with prolactin or melatonin interferes with the processes responsible for the development and maintenance of pregnancy.

Enhanced prolactin levels in opium smokers.

Science.gov (United States)

Moshtaghi-Kashanian, Ghollam-Reza; Esmaeeli, Farzaneh; Dabiri, Shahriar

2005-12-01

In Iran, opium is smoked for pleasure or as a medication by some people. It is a complex mixture of 40 different alkaloids, including morphine and codeine along with many impurities. Although it is well established that opioids or tobacco affect many physiological functions in humans, to our knowledge there has been no specific study looking at these effects in opium smokers. To assess that, we investigated the circulating levels of prolactin, TSH, LH, FSH and testosterone in male opium smokers who also smoke cigarettes (n=23, aged 28.4+/- 4.1 years), and comparing this with the corresponding values for nicotine abusers (n=12, 15-25 cigarettes/day) or a healthy control group (n=20) of the same age. Our results showed that 86.96% of the opium-dependent and 41.67 % of the nicotine-dependent group displayed high prolactin values (popium and the plasma prolactin level of opium dependents (p=0.748, popium smokers and 50% of the cigarette smokers (popium smokers was also lower than that of the other two groups (popium and cigarette smoking may synergistically influence pituitary hormone production through the effects on neuropeptides produced either locally or systemic.

Regulation of glucose transport and c-fos and egr-1 expression in cells with mutated or endogenous growth hormone receptors

DEFF Research Database (Denmark)

Gong, T W; Meyer, D J; Liao, J

1998-01-01

To identify mechanisms by which GH receptors (GHR) mediate downstream events representative of growth and metabolic responses to GH, stimulation by GH of c-fos and egr-1 expression and glucose transport activity were examined in Chinese hamster ovary (CHO) cells expressing mutated GHR. In CHO cel...

Methylmercury inhibits prolactin release in a cell line of pituitary origin

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L.A.L. Maués

2015-08-01

Full Text Available Heavy metals, such as methylmercury, are key environmental pollutants that easily reach human beings by bioaccumulation through the food chain. Several reports have demonstrated that endocrine organs, and especially the pituitary gland, are potential targets for mercury accumulation; however, the effects on the regulation of hormonal release are unclear. It has been suggested that serum prolactin could represent a biomarker of heavy metal exposure. The aim of this study was to evaluate the effect of methylmercury on prolactin release and the role of the nitrergic system using prolactin secretory cells (the mammosomatotroph cell line, GH3B6. Exposure to methylmercury (0-100 μM was cytotoxic in a time- and concentration-dependent manner, with an LC50 higher than described for cells of neuronal origin, suggesting GH3B6 cells have a relative resistance. Methylmercury (at exposures as low as 1 μM for 2 h also decreased prolactin release. Interestingly, inhibition of nitric oxide synthase by N-nitro-L-arginine completely prevented the decrease in prolactin release without acute neurotoxic effects of methylmercury. These data indicate that the decrease in prolactin production occurs via activation of the nitrergic system and is an early effect of methylmercury in cells of pituitary origin.

EGR technology for lowest emissions

NARCIS (Netherlands)

Baert, R.S.G.; Beckman, D.E.; Veen, A.

1996-01-01

An EGR system for turbocharged and aftercooled HD diesel engines has been demonstrated on a 12 litre 315 kW engine with 4 valves per cylinder and a high pressure injection system. In this system exhaust gas is tapped off before the turbine, run through a cooler and mixed with the intake air after

Pituitary Macroprolactinoma with Mildly Elevated Serum Prolactin: Hook Effect

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Mahnaz Pejman-Sani

2018-04-01

Full Text Available A 45-year-old man was admitted in our department with complaints of severe headache for over 6 months period. He also suffered from several problems such as visual field defect, decreased energy and libido, body hair loss, cold intolerance, decreased appetite and dry skin. On physical examination, he was afebrile: BP (blood pressure: 110/70 mm/Hg, PR (pulse rate :65 beat/min, BMI (body mass index: 24. He had no terminal hair on face or chest and subcutaneous adipose tissue mass had been decreased substantially. Laboratory tests revealed; Hb: 12 g/dL (N: 14–17 g/dL, Total testosterone: 1.2 ng/mL (N:–-10 ng/mL, Luteinizing hormone (LH:3.3MIU/mL (N:1–8 MIU/mL, Follicle Stimulating hormone (FSH:1.3 MIU/mL (N:1–7 MIU/mL, T4:3.4 micg/dL (N:4–12 micg/dL, TSH:0.6 MIU/mL (N:0.5–5 MIU/mL, Prolactin:100 ng/mL (2–24 ng/mL, serum cortisol:6 MIU/mL (N:4–21 MIU/mL, IGF1:162 ng/mL (50–245. Pituitary MRI showed macroadenoma (29*16*14 mm in left side of sella turcica which bulged to suprasellar cistern with pressure effect on left optic nerve (Figure 1, 2. Visual field examination revealed mild temporal hemianopia. These findings are consistent with macroadenoma and mild prolactin elevation. We also observed a discrepancy between pituitary tumor size and prolactin level. The correct estimate of serum prolactin was obtained after serial dilutional measurement. Serum prolactin after dilution was 6470 ng/mL. With these findings pituitary macroadenoma was diagnosed and treatment with cabergoline (dopamine agonist 0.5 mg/week was started. After one month follow-up he had no symptoms, visual field defect was improved and pituitary MRI showed significant shrinkage of tumor.

Dopamine inhibits maitotoxin-stimulated pituitary 45Ca2+ efflux and prolactin release

International Nuclear Information System (INIS)

Login, I.S.; Judd, A.M.; MacLeod, R.M.

1986-01-01

The authors examined the hypothesis that dopaminergic inhibition of prolactin release is coupled to modulation of cellular calcium flux. Dispersed female rat pituitary cells were prelabeled in 45 Ca 2+ and perifused to determine simultaneously fractional calcium efflux and prolactin release, as stimulated by maitotoxin, a calcium channel activator. The integrated response of each parameter to 5 ng/ml maitotoxin was obtained in individual perifusion columns in the absence or presence of various concentrations of dopamine. Maitotoxin-stimulated calcium efflux was suppressed by dopamine concentrations of 0.01 μM and greater and achieved a maximal effect at ∼0.1 μM, at which calcium efflux was reduced by 50%. Maitotoxin-stimulated prolactin release was inhibited by 0.03 μM dopamine and greater concentrations, and at a concentration of ∼10.0 μM dopamine the effect became maximal at ∼85% suppression. Haloperidol (0.1 μM) blocked the effects of 0.1 μM dopamine on both parameters. Simultaneous suppression of maitotoxin-stimulated calcium efflux and prolactin release by concentrations of dopamine within the nonomolar range suggests that dopamine receptor activation is negatively coupled to modulation of calcium flux in the physiological regulation of prolactin secretion

Night shift work and prolactin as a breast cancer risk factor

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Agnieszka Bukowska

2013-04-01

Full Text Available Prolactin - a hormone secreted in a circadian rhythm acts as a regulator of growth and development of the mammary glands. It has been observed that working at night increases breast cancer risk in women. Night shift work, probably carcinogenic to humans (Group 2A IARC, can disrupt a circadian rhythm, and thus potentially alter the rhythm of prolactin secretion. The aim of our work was to review epidemiological evidence on the association between prolactin and the risk of breast cancer and the influence of work at night on prolactin secretion. Search was done in the Medline database by keywords (shift work, work at night, risk of breast cancer and prolactin. The increased proliferation of breast cells activated by prolactin can promote the development of cancer. The results of the largest epidemiological prospective studies suggest the association between prolactin levels and the risk of breast cancer in women. So far, only seven studies have investigated the association between work at night and prolactin secretion. In three studies lower concentrations of prolactin have been observed in night shift workers. No relationship between the night shift work duration and prolactin level in women have been reported. Night shift work can modify the profile of prolactin secretion in night workers, probably decreasing the secretion of this hormone at night. It is therefore unlikely that prolactin plays an important role in the development of breast cancer in women working at night. This conclusion is based on the results of a few epidemiological studies. Med Pr 2013;64(2:245–257

Combustion and emission characteristics of a natural gas-fueled diesel engine with EGR

International Nuclear Information System (INIS)

Abdelaal, M.M.; Hegab, A.H.

2012-01-01

Highlights: ► An existed DI diesel engine has been modified to suit dual fuel operation with EGR. ► Comparative study has been conducted between different operating modes. ► Dual fuel mode exhibits better performance at high loads than diesel. ► Dual fuel mode exhibits lower NOx and higher HC emissions than diesel. ► EGR improves performance at part loads and emissions of dual fuel mode. - Abstract: The use of natural gas as a partial supplement for liquid diesel fuel is a very promising solution for reducing pollutant emissions, particularly nitrogen oxides (NOx) and particulate matters (PM), from conventional diesel engines. In most applications of this technique, natural gas is inducted or injected in the intake manifold to mix uniformly with air, and the homogenous natural gas–air mixture is then introduced to the cylinder as a result of the engine suction. This type of engines, referred to as dual-fuel engines, suffers from lower thermal efficiency and higher carbon monoxide (CO) and unburned hydrocarbon (HC) emissions; particularly at part load. The use of exhaust gas recirculation (EGR) is expected to partially resolve these problems and to provide further reduction in NOx emission as well. In the present experimental study, a single-cylinder direct injection (DI) diesel engine has been properly modified to run on dual-fuel mode with natural gas as a main fuel and diesel fuel as a pilot, with the ability to employ variable amounts of EGR. Comparative results are given for various operating modes; conventional diesel mode, dual-fuel mode without EGR, and dual-fuel mode with variable amounts of EGR, at different operating conditions; revealing the effect of utilization of EGR on combustion process and exhaust emission characteristics of a pilot ignited natural gas diesel engine.

Prolactin as a Marker of Successful Catheterization during IPSS in Patients with ACTH-Dependent Cushing's Syndrome

Science.gov (United States)

Sharma, S. T.; Raff, H.

2011-01-01

Context: Anomalous venous drainage can lead to false-negative inferior petrosal sinus sampling (IPSS) results. Baseline inferior petrosal sinus to peripheral (IPS/P) prolactin ratio higher than 1.8 ipsilateral to the highest ACTH ratio has been proposed to verify successful catheterization. Prolactin-normalized ACTH IPS/P ratios may differentiate Cushing's disease (CD) from ectopic ACTH syndrome (EAS). Objective: Our objective was to examine the utility of prolactin measurement during IPSS. Design, Setting, and Participants: We conducted a retrospective analysis of prolactin levels in basal and CRH-stimulated IPSS samples in ACTH-dependent Cushing's syndrome (2007–2010). Results: Twenty-five of 29 patients had a pathologically proven diagnosis (17 CD and eight EAS). IPSS results were partitioned into true positive for CD (n = 16), true negative (n = 7), false negative (n = 1), and false positive (n = 1). Prolactin IPS/P ratio suggested successful IPSS in eight of 11 with abnormal venograms. Baseline prolactin IPS/P ratio was helpful in two patients with abnormal venograms and false-negative (catheterization unsuccessful) or true-negative (catheterization successful) IPSS results; the normalized ratio correctly diagnosed their disease. Normalized ACTH IPS/P ratio was at least 1.3 in all with CD, but prolactin IPS/P ratios were misleadingly low in two. One patient with cyclic EAS had a false-positive IPSS when eucortisolemic (baseline prolactin IPS/P = 1.7; normalized ratio = 5.6). All other EAS patients had normalized ratios no higher than 0.7. Conclusion: Prolactin measurement and evaluation of the venogram can improve diagnostic accuracy when IPSS results suggest EAS but is not necessary with positive IPSS results. Confirmation of hypercortisolemia remains a prerequisite for IPSS. A normalized ratio of 0.7–1.3 was not diagnostic. PMID:22031511

Pak2 Controls Acquisition of NKT Cell Fate by Regulating Expression of the Transcription Factors PLZF and Egr2

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O’Hagan, Kyle L.; Zhao, Jie; Pryshchep, Olga; Wang, Chyung-Ru

2015-01-01

NKT cells constitute a small population of T cells developed in the thymus that produce large amounts of cytokines and chemokines in response to lipid Ags. Signaling through the Vα14-Jα18 TCR instructs commitment to the NKT cell lineage, but the precise signaling mechanisms that instruct their lineage choice are unclear. In this article, we report that the cytoskeletal remodeling protein, p21-activated kinase 2 (Pak2), was essential for NKT cell development. Loss of Pak2 in T cells reduced stage III NKT cells in the thymus and periphery. Among different NKT cell subsets, Pak2 was necessary for the generation and function of NKT1 and NKT2 cells, but not NKT17 cells. Mechanistically, expression of Egr2 and promyelocytic leukemia zinc finger (PLZF), two key transcription factors for acquiring the NKT cell fate, were markedly diminished in the absence of Pak2. Diminished expression of Egr2 and PLZF were not caused by aberrant TCR signaling, as determined using a Nur77-GFP reporter, but were likely due to impaired induction and maintenance of signaling lymphocyte activation molecule 6 expression, a TCR costimulatory receptor required for NKT cell development. These data suggest that Pak2 controls thymic NKT cell development by providing a signal that links Egr2 to induce PLZF, in part by regulating signaling lymphocyte activation molecule 6 expression. PMID:26519537

Prolactin suppresses malonyl-CoA concentration in human adipose tissue

DEFF Research Database (Denmark)

Nilsson, L. A.; Roepstorff, Carsten; Kiens, Bente

2009-01-01

Prolactin is best known for its involvement in lactation, where it regulates mechanisms that supply nutrients for milk production. In individuals with pathological hyperprolactinemia, glucose and fat homeostasis have been reported to be negatively influenced. It is not previously known, however......, whether prolactin regulates lipogenesis in human adipose tissue. The aim of this study was to investigate the effect of prolactin on lipogenesis in human adipose tissue in vitro. Prolactin decreased the concentration of malonyl-CoA, the product of the first committed step in lipogenesis, to 77......+/-6% compared to control 100+/-5% (p=0.022) in cultured human adipose tissue. In addition, prolactin was found to decrease glucose transporter 4 ( GLUT4) mRNA expression, which may cause decreased glucose uptake. In conclusion, we propose that prolactin decreases lipogenesis in human adipose tissue...

Combustion and emissions characteristics of high n-butanol/diesel ratio blend in a heavy-duty diesel engine and EGR impact

International Nuclear Information System (INIS)

Chen, Zheng; Wu, Zhenkuo; Liu, Jingping; Lee, Chiafon

2014-01-01

Highlights: • Effects of EGR on high n-butanol/diesel ratio blend (Bu40) were investigated and compared with neat diesel (Bu00). • Bu40 has higher NOx due to wider combustion high-temperature region. • Bu40 has lower soot due to local lower equivalence ratio distribution. • Bu40 has higher CO due to lower gas temperature in the late expansion process. • For Bu40, EGR reduces NOx emissions dramatically with no obvious influence on soot. - Abstract: In this work, the combustion and emission fundamentals of high n-butanol/diesel ratio blend with 40% butanol (i.e., Bu40) in a heavy-duty diesel engine were investigated by experiment and simulation at constant engine speed of 1400 rpm and an IMEP of 1.0 MPa. Additionally, the impact of EGR was evaluated experimentally and compared with neat diesel fuel (i.e., Bu00). The results show that Bu40 has higher cylinder pressure, longer ignition delay, and faster burning rate than Bu00. Compared with Bu00, moreover, Bu40 has higher NOx due to wider combustion high-temperature region, lower soot due to local lower equivalence ratio distribution, and higher CO due to lower gas temperature in the late expansion process. For Bu40, EGR reduces NOx emissions dramatically with no obvious influence on soot. Meanwhile, there is no significant change in HC and CO emissions and indicated thermal efficiency (ITE) with EGR until EGR threshold is reached. When EGR rate exceeds the threshold level, HC and CO emissions increase dramatically, and ITE decreases markedly. Compared with Bu00, the threshold of Bu40 appears at lower EGR rate. Consequently, combining high butanol/diesel ratio blend with medium EGR has the potential to achieve ultra-low NOx and soot emissions simultaneously while maintaining high thermal efficiency level

A numerical investigation on the influence of EGR in a supercharged SI engine fueled with gasoline and alternative fuels

International Nuclear Information System (INIS)

Mardi K, Mohsen; Khalilarya, Shahram; Nemati, Arash

2014-01-01

Highlights: • CFD modeling the combustion of different alternative fuels in SI engine. • 10% of EGR is the most desirable amount from the viewpoint of emissions and power. • EGR affects on methane fuel more than others. • Supercharging has the most noticeable effect on gasoline fuel and the least on hydrogen fuel. - Abstract: Alternative fuels are mostly extracted from renewable resources, and their emission levels can be lower than those of traditional fossil-based fuels. A computational fluid dynamics (CFD) method is utilized to investigate the effects of exhaust gas recirculation (EGR) and initial charge pressure on the emissions and performance of a SI engine. The engine is fueled separately by gasoline and some of potential alternative fuels including hydrogen, propane, methane, ethanol and methanol. The results of simulation are compared to the experimental data. In all validation cases, experimental and numerical results were observed to have good agreement with each other. The calculations are carried out for EGR ratios between 0% and 20% and four cases of initial pressure have been mentioned: P in = 1, 1.2, 1.4, 1.6 bar. The effect of EGR on NO x emission of methane is more than other fuels and its effect on IMEP of hydrogen is less than other fuels. From the viewpoints of emission and power, 10% of EGR seems to be the most desirable amount. The most noticeable effect of supercharging is on gasoline unlike hydrogen, which seems to be affected the least. The comparison of results shows that hydrogen due to its high heating value and burning without producing any carbon-based compounds such as HC, CO and CO 2 is an ideal alternative fuel compared to the other fuels

Carbon monoxide induced PPARγ SUMOylation and UCP2 block inflammatory gene expression in macrophages.

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Arvand Haschemi

Full Text Available Carbon monoxide (CO dampens pro-inflammatory responses in a peroxisome proliferator-activated receptor-γ (PPARγ and p38 mitogen-activated protein kinase (MAPK dependent manner. Previously, we demonstrated that CO inhibits lipopolysaccharide (LPS-induced expression of the proinflammatory early growth response-1 (Egr-1 transcription factor in macrophages via activation of PPARγ. Here, we further characterize the molecular mechanisms by which CO modulates the activity of PPARγ and Egr-1 repression. We demonstrate that CO enhances SUMOylation of PPARγ which we find was attributed to mitochondrial ROS generation. Ectopic expression of a SUMOylation-defective PPARγ-K365R mutant partially abolished CO-mediated suppression of LPS-induced Egr-1 promoter activity. Expression of a PPARγ-K77R mutant did not impair the effect of CO. In addition to PPARγ SUMOylation, CO-activated p38 MAPK was responsible for Egr-1 repression. Blocking both CO-induced PPARγ SUMOylation and p38 activation, completely reversed the effects of CO on inflammatory gene expression. In primary macrophages isolated form C57/BL6 male mice, we identify mitochondrial ROS formation by CO as the upstream trigger for the observed effects on Egr-1 in part through uncoupling protein 2 (UCP2. Macrophages derived from bone marrow isolated from Ucp2 gene Knock-Out C57/BL6 mice (Ucp2(-/-, produced significantly less ROS with CO exposure versus wild-type macrophages. Moreover, absence of UCP2 resulted in a complete loss of CO mediated Egr-1 repression. Collectively, these results indentify p38 activation, PPARγ-SUMOylation and ROS formation via UCP2 as a cooperative system by which CO impacts the inflammatory response.

New EGR technology retains HD diesel economy with 21st century emissions

NARCIS (Netherlands)

Baert, R.S.G.; Beckman, D.E.; Verbeek, R.P.

1996-01-01

An EGR system for turbocharged (and aftercooled) heavy-duty diesel engines have been demonstrated on a 12 litre 315 kW engine with 4 valves per cyclinder head and high pressure injection system. In the EGR system exhaust gas is tapped of before the turbine, run through a cooler and mixed with the

Circulating prolactin level in systemic lupus erythematosus and its correlation with disease activity: a meta-analysis.

Science.gov (United States)

Song, G G; Lee, Y H

2017-10-01

Objective This study aimed to evaluate the relationship between circulating prolactin level and systemic lupus erythematosus (SLE), and to establish a correlation between plasma/serum prolactin levels and SLE activity. Methods We performed a meta-analysis comparing the plasma/serum prolactin levels in patients with SLE to controls, and examined correlation coefficients between circulating prolactin level and SLE disease activity. Results Twenty-five studies with a total of 1056 SLE patients and 426 controls were included. Prolactin levels were significantly higher overall in the SLE group than in the control group (standardized mean difference (SMD) = 0.987, 95% CI = 0.512-1.463, p = 4.7 × 10 -5 ). Stratification by ethnicity showed significantly elevated prolactin levels in the SLE group in Asian, Latin American, and mixed populations (SMD = 0.813, 95% CI = 0.137-1.490, p = 0.018; SMD = 0.981, 95% CI = 0.307-1.655, p = 0.004; SMD = 1.469, 95% CI = 0.443-2.495, p = 0.005, respectively), but not in the European population. Subgroup analysis by sample size showed significantly higher prolactin levels in the SLE group by small ( n  30). Meta-analysis of correlation coefficients showed a significantly positive correlation between circulating prolactin level and SLE activity (correlation coefficient = 0.379, 95% CI = 0.026-0.487, p = 4.0 × 10 -9 ). Circulating prolactin levels were positively associated with SLE activity in European, Asian, and mixed populations (SMD = 0.532, 95% CI = 0.443-0.609  p < 1.0 × 10 -8 ; SMD = 0.427, 95% CI = 0.240-0.583, p = 2.4 × 10 -5 ; SMD = 0.433, 95% CI = 0.212-0.591, p = 2.7 × 10 -5 , respectively). Conclusions Our meta-analysis demonstrated that circulating prolactin levels are higher in patients with SLE, and that a significantly positive correlation exists between prolactin levels and SLE activity.

Non-opiate [beta]-endorphin fragments and dopamine--V [gamma]-type endorphins and prolactin secretion in rats

NARCIS (Netherlands)

Lamberts, S.W.J.; De Quijada, M.; Ree, J.M. van; Wied, D. de

1982-01-01

The effects on prolactin secretion of three peptide-derivatives of β-endorphin which show neuroleptic-like activities in rats were studied. Intravenous administration of γ-endorphin (β-endorphin (βE) 1–17) enhanced plasma prolactin levels. γ-Endorphin did not affect the prolactin secretion by

Real-time CO2 sensor for the optimal control of electronic EGR system

Science.gov (United States)

Kim, Gwang-jung; Choi, Byungchul; Choi, Inchul

2013-12-01

In modern diesel engines, EGR (Exhaust Gas Recirculation) is an important technique used in nitrogen oxide (NOx) emission reduction. This paper describes the development and experimental results of a fiber-optical sensor using a 2.7 μm wavelength absorption to quantify the simultaneous CO2 concentration which is the primary variable of EGR rate (CO2 in the exhaust gas versus CO2 in the intake gas, %). A real-time laser absorption method was developed using a DFB (distributed feedback) diode laser and waveguide to make optimal design and control of electronic EGR system required for `Euro-6' and `Tier 4 Final' NOx emission regulations. While EGR is effective to reduce NOx significantly, the amount of HC and CO is increased in the exhaust gas if EGR rate is not controlled based on driving conditions. Therefore, it is important to recirculate an appropriate amount of exhaust gas in the operation condition generating high volume of NOx. In this study, we evaluated basic characteristics and functions of our optical sensor and studied basically in order to find out optimal design condition. We demonstrated CO2 measurement speed, accuracy and linearity as making a condition similar to real engine through the bench-scale experiment.

Comparison of alterations in c-fos and Egr-1 (zif268) expression throughout the rat brain following acute administration of different classes of antidepressant compounds.

Science.gov (United States)

Slattery, David A; Morrow, John A; Hudson, Alan L; Hill, David R; Nutt, David J; Henry, Brian

2005-07-01

The majority of immediate-early gene (IEG) studies focus on a few key brain regions associated with the class of psychoactive compound being studied. Recently, using a meta-analysis of the c-fos literature, we demonstrated the utility of c-fos profiling to classify such compounds. The present study examined acute delivery of a range of antidepressant classes; fluoxetine, imipramine, LiCl, and mirtazapine. The dual aims were to study the IEG profiles of these varying classes of antidepressants throughout the rat brain and to compare the utility of c-fos or Egr-1 as IEGs to classify clinically efficacious antidepressants. All antidepressants increased c-fos mRNA in the central amygdala, as previously shown, while c-fos was also increased in the anterior insular cortex and significantly decreased within the septum. Although acute antidepressant administration altered c-fos expression in a number of brain regions, Egr-1 expression was only significantly altered in the central amygdala, suggesting that Egr-1 may not be as useful a marker to investigate acute antidepressant treatment. The fact that these drugs, including the previously unclassified antidepressant mirtazapine, share a number of common loci of activation, which are implicated by human and animal studies in depression, adds further support to the use of IEG mapping to classify psychoactive compounds.

Prolactin and Psychopathology in Schizophrenia: A Literature Review and Reappraisal

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Ravi Philip Rajkumar

2014-01-01

Full Text Available Secretion of the anterior pituitary hormone prolactin can be significantly increased by antipsychotic drugs, leading to a range of adverse effects in patients with schizophrenia. However, there is evidence from a variety of studies that prolactin may also be related to symptom profile and treatment response in these patients, and recent work has identified variations in prolactin secretion even in drug-free patients. In this paper, a selective review of all relevant studies pertaining to prolactin and schizophrenia, including challenge and provocation studies, is presented. The implications of this work are discussed critically. A tentative model, which synthesizes these findings and argues for a significant role for prolactin in the development of schizophrenia, is outlined.

Seasonal prolactin secretion and its role in seasonal reproduction: a review.

Science.gov (United States)

Curlewis, J D

1992-01-01

The majority of seasonally breeding mammals show a seasonal pattern of prolactin secretion with peak concentrations in spring or summer and a nadir in autumn or winter. Photoperiod influences prolactin secretion via its effects on the secretion of the pineal hormone melatonin. Preliminary evidence suggests that the effects of melatonin on both prolactin and gonadotrophin secretion are via a common target area, possibly within the anterior hypothalamus, and that differences in response to photoperiod may be due to differences in the processing and/or interpretation of the melatonin signal. In contrast to seasonal gonadotrophin secretion, the seasonal changes in prolactin are not due to changes in the sensitivity of a feedback loop and so must be due to direct effects on the hypothalamic pathways that control prolactin secretion. Little else can be said with confidence about the neuroendocrine mechanisms that lead to the seasonal changes in prolactin secretion. Dopamine and noradrenaline turnover in the arcuate nucleus and median eminence decrease under short daylength. If catecholamine turnover in these structures is positively correlated with catecholamine concentrations in the long or short hypophysial portal vessels, it is unlikely that the decrease in prolactin concentration in winter is due to the effects of increased concentrations of dopamine or noradrenaline in the portal vessels. There is, however, evidence for increased pituitary sensitivity to dopamine under short daylength, so increased dopamine concentrations may not be required for suppression of prolactin secretion at this time. In addition to the diminished secretion of prolactin under short daylength, rate of prolactin synthesis and pituitary content of prolactin also decline although the mechanisms that regulate these changes are poorly understood. Although all seasonal breeders show a seasonal change in prolactin secretion, there are continuously breeding species in which prolactin secretion is

Effects of chronic alternating cadmium exposure on the episodic secretion of prolactin in male rats

Energy Technology Data Exchange (ETDEWEB)

Esquifino, A.I. [Madrid Univ. (Spain). Facultad de Medicina Complutense; Marquez, N.; Alvarez-Demanuel, E.; Lafuente, A. [Vigo Univ., Orense (Spain). Lab. de Toxicologia

1998-07-01

Cadmium increases or decreases prolactin secretion depending on the dose and duration of the exposure to the metal. However, whether there are cadmium effects on the episodic prolactin secretion is less well known. This study was undertaken to address whether chronic alternating exposure to two different doses of cadmium affects the episodic pattern of prolactin and to what extent the effects of cadmium are age-dependent. Male rats were treated s.c. with cadmium chloride (0.5 or 1.0 mg/kg) from day 30 to 60, or from day 60 to 90 of age, with alteration of the doses every 4 days, starting with the smaller dose. Controls received vehicle every 4 days. The last dose of cadmium was given 48 h prior to the pulsatility study. Prolactin secretion in the 4 experimental groups studied was episodic and changed significantly after cadmium exposure. Cadmium administration from day 30 to 60 of life significantly decreased the mean half-life of prolactin. On the other hand, when administered from day 60 to 90 cadmium significantly decreased the mean as well as serum prolactin levels and the absolute amplitude of the prolactin pulses, their duration, the relative amplitude or the mean half-life of the hormone. The frequency of prolactin peaks was not changed by cadmium administration. The results indicate that low intermittent doses of cadmium chronically administered change the episodic secretion pattern of prolactin in rats. The effects of cadmium on prolactin secretion were age dependent. (orig.)

Evaluation of the human prolactin of National Production for use in radioimmunoassay (RIA)

International Nuclear Information System (INIS)

Caso, R.; Arranz, C.

1996-01-01

In this work was studied the possibility of using the Prolactin hormone as raw material to produce Kits-RIA of Prolactin. Was used the prolactin, which is obtained in Cuba by the Pharmaceutical Institute Mario Munoz. Was made the labbeling of Prolactin with I-125, was used the hormone as standard and were done the probes of quality control. The Prolactin Hormone had the necesary quality to produce Kits-RIA-Prolactin

Activation of Tax protein by c-Jun-N-terminal kinase is not dependent on the presence or absence of the early growth response-1 gene product.

Science.gov (United States)

Parra, Eduardo; Gutierréz, Luís; Ferreira, Jorge

2016-02-01

The Tax protein of human T cell leukemia virus type 1 plays a major role in the pathogenesis of adult T cell leukemia (ATL), an aggressive neoplasia of CD4+ T cells. In the present study, we investigated whether the EGR-1 pathway is involved in the regulation of Tax-induced JNK expression in human Jurkat T cells transfected to express the Tax protein in the presence or absence of PMA or ionomycin. Overexpression of EGR-1 in Jurkat cells transfected to express Tax, promoted the activation of several genes, with the most potent being those that contained AP-1 (Jun/c-Fos), whereas knockdown of endogenous EGR-1 by small interfering RNA (siRNA) somewhat reduced Tax-mediated JNK-1 transcription. Additionally, luciferase-based AP-1 and NF-κB reporter gene assays demonstrated that inhibition of EGR-1 expression by an siRNA did not affect the transcriptional activity of a consensus sequence of either AP-1 or NF-κB. On the other hand, the apoptosis assay, using all-trans retinoic acid (ATRA) as an inducer of apoptosis, confirmed that siRNA against EGR-1 failed to suppress ATRA-induced apoptosis in Jurkat and Jurkat-Tax cells, as noted by the low levels of both DEVDase activity and DNA fragmentation, indicating that the induction of apoptosis by ATRA was Egr-1-independent. Finally, our data showed that activation of Tax by JNK-1 was not dependent on the EGR-1 cascade of events, suggesting that EGR-1 is important but not a determinant for the activity for Tax-induced proliferation of Jurkat cells.

Experimental investigations of effects of EGR on performance and emissions characteristics of CNG fueled reactivity controlled compression ignition (RCCI) engine

International Nuclear Information System (INIS)

Singh Kalsi, Sunmeet; Subramanian, K.A.

2016-01-01

Highlights: • NO_x emission decreased drastically in RCCI engine with EGR. • CO and HC emissions decreased with 8% EGR. • Smoke emission increased with EGR but is still less than base diesel. • Brake thermal efficiency does not change with EGR up to 15% • 8% EGR is optimum based on less CO, HC, NO_x except smoke. - Abstract: Experimental: tests were carried out on a single cylinder diesel engine (7.4 kW rated power at 1500 rpm) under dual fuel mode (CNG-Diesel) with EGR (exhaust gas recirculation). Less reacting fuel (CNG) was injected inside the intake manifold using timed manifold gas injection system whereas high reactive diesel fuel was directly injected into the engine’s cylinder for initiation of ignition. EGR at different percentages (8%, 15% and 30%) was inducted to the engine through intake manifold and tests were conducted at alternator power output of 2 kW and 5 kW. The engine can operate under dual fuel mode with maximum CNG energy share of 85% and 92% at 5 kW and 2 kW respectively. The brake thermal efficiency of diesel engine improved marginally at 5 kW power output under conventional dual fuel mode with the CNG share up to 37% whereas the efficiency did not change with up to 15% EGR however it decreased beyond the EGR percentage. NO_x emission in diesel engine under conventional dual fuel mode decreased significantly and it further decreased drastically with EGR. The notable point emerged from this study is that CO and HC emissions, which are major problems at part load in reactivity controlled compression ignition engine (RCCI), decreased with 8% EGR along with further reduction of NO_x. However, smoke emission is marginally higher with EGR than without EGR but it is still less than conventional mode (Diesel alone). The new concept emerged from this study is that CO and HC emissions of RCCI engine at part load can be reduced using EGR.

The hormone prolactin is a novel, endogenous trophic factor able to regulate reactive glia and to limit retinal degeneration.

Science.gov (United States)

Arnold, Edith; Thebault, Stéphanie; Baeza-Cruz, German; Arredondo Zamarripa, David; Adán, Norma; Quintanar-Stéphano, Andrés; Condés-Lara, Miguel; Rojas-Piloni, Gerardo; Binart, Nadine; Martínez de la Escalera, Gonzalo; Clapp, Carmen

2014-01-29

Retinal degeneration is characterized by the progressive destruction of retinal cells, causing the deterioration and eventual loss of vision. We explored whether the hormone prolactin provides trophic support to retinal cells, thus protecting the retina from degenerative pressure. Inducing hyperprolactinemia limited photoreceptor apoptosis, gliosis, and changes in neurotrophin expression, and it preserved the photoresponse in the phototoxicity model of retinal degeneration, in which continuous exposure of rats to bright light leads to retinal cell death and retinal dysfunction. In this model, the expression levels of prolactin receptors in the retina were upregulated. Moreover, retinas from prolactin receptor-deficient mice exhibited photoresponsive dysfunction and gliosis that correlated with decreased levels of retinal bFGF, GDNF, and BDNF. Collectively, these data unveiled prolactin as a retinal trophic factor that may regulate glial-neuronal cell interactions and is a potential therapeutic molecule against retinal degeneration.

Experimental study on anti-tumor effect of pcEgr-IFNγ gene-radiotherapy

International Nuclear Information System (INIS)

Wu Congmei; Li Xiuyi; Liu Shuzheng

2001-01-01

Objective: To study the anti-tumor effect of IFN γ gene-radiotherapy to murine melanoma and its immunologic mechanism. Methods: pcEgr-IFNγ plasmids were injected locally into tumor, and 36 hours later, the tumors were given 20 Gy X-ray irradiation. Tumor growth at different time, IFN γ expression 3 days later and immunologic indexes 15 days later were detected. Results: At 3-15 days after pcEgr-IFNγ gene-radiotherapy, the tumor growth rate was lower than that of irradiation alone group. It was also lower than that of gene therapy alone group and control plasmid combined with X-ray irradiation group significantly. Day 3 tumor IFN γ expression was higher than that of plasmid treatment alone group. NK activity, IL-2 and IFN γ secretion activities were higher than those of gene therapy alone and irradiation alone groups significantly. Conclusion: The antitumor effect of IFN γ gene-radiotherapy is better than that of either of them applied solely. Its mechanism might be concerned with the higher expression of IFN γ induced by irradiation in tumors and activation of anti-tumor immunologic functions

Hypergravity and estrogen effects on avian anterior pituitary growth hormone and prolactin levels

Science.gov (United States)

Fiorindo, R. P.; Negulesco, J. A.

1980-01-01

Developing female chicks with fractured right radii were maintained for 14 d at either earth gravity (1 g) or a hypergravity state (2 g). The birds at 1 g were divided into groups which received daily injections of (1) saline, (2) 200 micrograms estrone, and (3) 400 micrograms estrone for 14 d. The 2-g birds were divided into three similarly treated groups. All 2-g birds showed significantly lower body weights than did 1-g birds. Anterior pituitary (AP) glands were excised and analyzed for growth hormone and prolactin content by analytical electrophoresis. The 1-g chicks receiving either dose of daily estrogen showed increased AP growth hormone levels, whereas hypergravity alone did not affect growth hormone content. Chicks exposed to daily estrogen and hypergravity displayed reduced growth hormone levels. AP prolactin levels were slightly increased by the lower daily estrogen dose in 1-g birds, but markedly reduced in birds exposed only to hypergravity. Doubly-treated chicks displayed normal prolactin levels. Reduced growth in 2-g birds might be due, in part, to reduced AP levels of prolactin and/or growth hormone.

Pak2 Controls Acquisition of NKT Cell Fate by Regulating Expression of the Transcription Factors PLZF and Egr2.

Science.gov (United States)

O'Hagan, Kyle L; Zhao, Jie; Pryshchep, Olga; Wang, Chyung-Ru; Phee, Hyewon

2015-12-01

NKT cells constitute a small population of T cells developed in the thymus that produce large amounts of cytokines and chemokines in response to lipid Ags. Signaling through the Vα14-Jα18 TCR instructs commitment to the NKT cell lineage, but the precise signaling mechanisms that instruct their lineage choice are unclear. In this article, we report that the cytoskeletal remodeling protein, p21-activated kinase 2 (Pak2), was essential for NKT cell development. Loss of Pak2 in T cells reduced stage III NKT cells in the thymus and periphery. Among different NKT cell subsets, Pak2 was necessary for the generation and function of NKT1 and NKT2 cells, but not NKT17 cells. Mechanistically, expression of Egr2 and promyelocytic leukemia zinc finger (PLZF), two key transcription factors for acquiring the NKT cell fate, were markedly diminished in the absence of Pak2. Diminished expression of Egr2 and PLZF were not caused by aberrant TCR signaling, as determined using a Nur77-GFP reporter, but were likely due to impaired induction and maintenance of signaling lymphocyte activation molecule 6 expression, a TCR costimulatory receptor required for NKT cell development. These data suggest that Pak2 controls thymic NKT cell development by providing a signal that links Egr2 to induce PLZF, in part by regulating signaling lymphocyte activation molecule 6 expression. Copyright © 2015 by The American Association of Immunologists, Inc.

Development and characterization of a homologous radioimmunoassay for equine prolactin

International Nuclear Information System (INIS)

Roser, J.F.; Chang, Y.S.; Papkoff, H.; Li, C.H.

1984-01-01

A specific and sensitive homologous radioimmunoassay has been developed for equine prolactin, suitable for measuring prolactin concentrations in serum of horses. The sensitivity of the assay ranged from 0.4 to 0.6 ng/ml and the intra- and inter-assay coefficients of variation averaged 6.9 and 15.4%, respectively, for five doses of hormone. Cross-reactivity with other mammalian and nonmammalian prolactins and growth hormones was less than 20 and 0.3%, respectively. Cross-reactivity with equine growth hormone was less than 0.07%. Equine serum and pituitary extracts showed parallel dilution-response curves with equine prolactin. The percentage recovery of exogenous equine prolactin in serum was 89%. Preliminary analysis of several physiological samples (stallions, pregnant, and nonpregnant mares) yielded values from 0.6 to 12.0 ng/ml

Odor discrimination learning in the Indian greater short-nosed fruit bat (Cynopterus sphinx): differential expression of Egr-1, C-fos and PP-1 in the olfactory bulb, amygdala and hippocampus.

Science.gov (United States)

Mukilan, Murugan; Bogdanowicz, Wieslaw; Marimuthu, Ganapathy; Rajan, Koilmani Emmanuvel

2018-04-19

Activity-dependent expression of immediate-early genes (IEGs) is induced by exposure to odor. The present study was designed to investigate whether there is differential expression of IEGs ( Egr-1 , C-fos ) in the brain region mediating olfactory memory in the Indian greater short-nosed fruit bat Cynopterus sphinx We assumed that differential expression of IEGs in different brain regions may orchestrate a preference odor (PO) and aversive odor (AO) memory in C. sphinx We used preferred (0.8% wt/wt of cinnamon powder) and aversive (0.4% wt/vol of citral) odor substances, with freshly-prepared chopped apple, to assess the behavioural response and induction of IEGs in the olfactory bulb, hippocampus and amygdala. After experiencing PO and AO, the bats initially responded to both, later only engaging in feeding bouts in response to the PO food. The expression pattern of Egr-1 and C-fos in the olfactory bulb, hippocampus and amygdala was similar at different time points (15, 30 and 60 min) following the response to PO, but different for AO. The response to AO elevated the level of C-fos expression within 30 min and reduced it at 60 min in both the olfactory bulb and the hippocampus, as opposed to the continuous increase noted in the amygdala. In addition, we tested whether an epigenetic mechanism entailing protein phosphatase-1 (PP-1) acts on IEG expression. The observed PP-1 expression and the level of unmethylated/methylated promoter revealed that the C-fos expression is possibly controlled by an odor-mediated regulation of PP-1. These results in turn imply that the differential expression of C-fos in the hippocampus and amygdala may contribute to olfactory learning and memory in C. sphinx . © 2018. Published by The Company of Biologists Ltd.

System Properties and Control of Turbocharged Diesel Engines with High-and Low-Pressure EGR Propriétés système et contrôle de moteurs Diesel turbocompressés avec EGR haute et basse pression

Directory of Open Access Journals (Sweden)

Mrosek M.

2011-09-01

Full Text Available An extension of the air-and exhaust-system with a low-pressure EGR has the potential to significantly reduce the NOx emissions. Besides a cooled high-pressure EGR and the turbocharger with variable geometry turbine, the low-pressure EGR introduces an additional degree of freedom to control the cylinder charge. This increasing complexity of the air system can be handled with model based control structures and a model based controller calibration. Its static and dynamic properties are investigated. Besides the static couplings in the classical air path, additional couplings appear. A decentralised gain scheduled PI(D-control approach is chosen to control the variables air mass flow rate, high-pressure EGR mass flow rate and charge air pressure. An automated controller calibration, based on a semi-physical mean value model of reduced complexity, is presented. The controller maps depend on the engine operation point and are calibrated by a local linearisation of the semi-physical model. Further, a semi-physical control is capable to almost solely control the air mass flow rate via the low-pressure EGR actuators. This control implicitly accounts for couplings between charge air pressure, high-pressure EGR and the low-pressure EGR system. Finally testbed results are shown. Une extension du système d’air et d’échappement au moyen d’EGR basse pression peut potentiellement réduire significativement les émissions de NOx. À côté de l’EGR haute pression refroidi et du turbocompresseur à turbine à géométrie variable, l’EGR basse pression introduit un degré de liberté supplémentaire pour contrôler la charge du cylindre. Cette complexité croissante du système d’air peut être traitée à l’aide de structures de contrôle et d’un étalonnage de régulateur basés sur des modèles. Ses propriétés statiques et dynamiques sont étudiées. En dehors des couplages statiques dans la boucle d’air classique, des couplages

A Single Dose of LSD Does Not Alter Gene Expression of the Serotonin 2A Receptor Gene (HTR2A) or Early Growth Response Genes (EGR1-3) in Healthy Subjects

Science.gov (United States)

Dolder, Patrick C.; Grünblatt, Edna; Müller, Felix; Borgwardt, Stefan J.; Liechti, Matthias E.

2017-01-01

Rationale: Renewed interest has been seen in the use of lysergic acid diethylamide (LSD) in psychiatric research and practice. The repeated use of LSD leads to tolerance that is believed to result from serotonin (5-HT) 5-HT2A receptor downregulation. In rats, daily LSD administration for 4 days decreased frontal cortex 5-HT2A receptor binding. Additionally, a single dose of LSD acutely increased expression of the early growth response genes EGR1 and EGR2 in rat and mouse brains through 5-HT2A receptor stimulation. No human data on the effects of LSD on gene expression has been reported. Therefore, we investigated the effects of single-dose LSD administration on the expression of the 5-HT2A receptor gene (HTR2A) and EGR1-3 genes. Methods: mRNA expression levels were analyzed in whole blood as a peripheral biomarker in 15 healthy subjects before and 1.5 and 24 h after the administration of LSD (100 μg) and placebo in a randomized, double-blind, placebo-controlled, cross-over study. Results: LSD did not alter the expression of the HTR2A or EGR1-3 genes 1.5 and 24 h after administration compared with placebo. Conclusion: No changes were observed in the gene expression of LSD’s primary target receptor gene or genes that are implicated in its downstream effects. Remaining unclear is whether chronic LSD administration alters gene expression in humans. PMID:28701958

EGR distribution and fluctuation probe based on CO.sub.2 measurements

Science.gov (United States)

Parks, II, James E; Partridge, Jr., William P; Yoo, Ji Hyung

2015-04-07

A diagnostic system having a single-port EGR probe and a method for using the same. The system includes a light source, an EGR probe, a detector and a processor. The light source may provide a combined light beam composed of light from a mid-infrared signal source and a mid-infrared reference source. The signal source may be centered at 4.2 .mu.m and the reference source may be centered at 3.8 .mu.m. The EGR probe may be a single-port probe with internal optics and a sampling chamber with two flow cells arranged along the light path in series. The optics may include a lens for focusing the light beam and a mirror for reflecting the light beam received from a pitch optical cable to a catch optical cable. The signal and reference sources are modulated at different frequencies, thereby allowing them to be separated and the signal normalized by the processor.

Receptor-like protein-tyrosine phosphatase alpha specifically inhibits insulin-increased prolactin gene expression

DEFF Research Database (Denmark)

Jacob, K K; Sap, J; Stanley, F M

1998-01-01

A physiologically relevant response to insulin, stimulation of prolactin promoter activity in GH4 pituitary cells, was used as an assay to study the specificity of protein-tyrosine phosphatase function. Receptor-like protein-tyrosine phosphatase alpha (RPTPalpha) blocks the effect of insulin...... is specific by two criteria. A number of potential RPTPalpha targets were ruled out by finding (a) that they are not affected or (b) that they are not on the pathway to insulin-increased prolactin-CAT activity. The negative effect of RPTPalpha on insulin activation of the prolactin promoter is not due...... to reduced phosphorylation or kinase activity of the insulin receptor or to reduced phosphorylation of insulin receptor substrate-1 or Shc. Inhibitor studies suggest that insulin-increased prolactin gene expression is mediated by a Ras-like GTPase but is not mitogen-activated protein kinase dependent...

Combined effects of cooled EGR and a higher geometric compression ratio on thermal efficiency improvement of a downsized boosted spark-ignition direct-injection engine

International Nuclear Information System (INIS)

Su, Jianye; Xu, Min; Li, Tie; Gao, Yi; Wang, Jiasheng

2014-01-01

Highlights: • Experiments for the effects of cooled EGR and two compression ratios (CR) on fuel efficiency were conducted. • The mechanism for the observed fuel efficiency behaviors by cooled EGR and high CR was clarified. • Cooled EGR offers more fuel efficiency improvement than elevating CR from 9.3 to 10.9. • Combining 18–25% cooled EGR with 10.9 CR lead to 2.1–3.5% brake thermal efficiency improvements. - Abstract: The downsized boosted spark-ignition direct-injection (SIDI) engine has proven to be one of the most promising concepts to improve vehicle fuel economy. However, the boosted engine is typically designed at a lower geometric compression ratio (CR) due to the increased knock tendency in comparison to naturally aspirated engines, limiting the potential of improving fuel economy. On the other hand, cooled exhaust gas recirculation (EGR) has drawn attention due to the potential to suppress knock and improve fuel economy. Combing the effects of boosting, increased CR and cooled EGR to further improve fuel economy within acceptable knock tolerance has been investigated using a 2.0 L downsized boosted SIDI engine over a wide range of engine operating conditions from 1000 rpm to 3000 rpm at low to high loads. To clarify the mechanism of this complicated effects, the first law of thermodynamics analysis was conducted with the inputs from GT-Power® engine simulation. Experiment results indicate that cooled EGR provides more brake thermal efficiency improvement than increasing geometric CR from 9.3 to 10.9. The benefit of brake thermal efficiency from the higher CR is limited to low load conditions. The attributes for improving brake thermal efficiency by cooled EGR include reduced heat transfer loss, reduced pumping work and increased ratio of specific heats for all the engine operating conditions, as well as higher degree of constant volume heat release only for the knock-limited high load conditions. The combined effects of 18–25% cooled EGR

An EGR performance evaluation and decision-making approach based on grey theory and grey entropy analysis.

Science.gov (United States)

Zu, Xianghuan; Yang, Chuanlei; Wang, Hechun; Wang, Yinyan

2018-01-01

Exhaust gas recirculation (EGR) is one of the main methods of reducing NOX emissions and has been widely used in marine diesel engines. This paper proposes an optimized comprehensive assessment method based on multi-objective grey situation decision theory, grey relation theory and grey entropy analysis to evaluate the performance and optimize rate determination of EGR, which currently lack clear theoretical guidance. First, multi-objective grey situation decision theory is used to establish the initial decision-making model according to the main EGR parameters. The optimal compromise between diesel engine combustion and emission performance is transformed into a decision-making target weight problem. After establishing the initial model and considering the characteristics of EGR under different conditions, an optimized target weight algorithm based on grey relation theory and grey entropy analysis is applied to generate the comprehensive evaluation and decision-making model. Finally, the proposed method is successfully applied to a TBD234V12 turbocharged diesel engine, and the results clearly illustrate the feasibility of the proposed method for providing theoretical support and a reference for further EGR optimization.

Distress call-induced gene expression in the brain of the Indian short-nosed fruit bat, Cynopterus sphinx.

Science.gov (United States)

Ganesh, Ambigapathy; Raghuram, Hanumanthan; Nathan, Parthasarathy T; Marimuthu, Ganapathy; Rajan, Koilmani Emmanuvel

2010-02-01

Individuals in distress emit audible vocalizations to either warn or inform conspecifics. The Indian short-nosed fruit bat, Cynopterus sphinx, emits distress calls soon after becoming entangled in mist nets, which appear to attract conspecifics. Phase I of these distress calls is longer and louder, and includes a secondary peak, compared to phase II. Activity-dependent expression of egr-1 was examined in free-ranging C. sphinx following the emissions and responses to a distress call. We found that the level of expression of egr-1 was higher in bats that emitted a distress call, in adults that responded, and in pups than in silent bats. Up-regulated cDNA was amplified to identify the target gene (TOE1) of the protein Egr-1. The observed expression pattern Toe1 was similar to that of egr-1. These findings suggest that the neuronal activity related to recognition of a distress call and an auditory feedback mechanism induces the expression of Egr-1. Co-expression of egr-1 with Toe1 may play a role in initial triggering of the genetic mechanism that could be involved in the consolidation or stabilization of distress call memories.

A heterologous radioimmunoassay for avian prolactin: Application to the measurement of prolactin in the turkey

International Nuclear Information System (INIS)

McNeilly, A.S.; Etches, R.J.; Friesen, H.G.

1978-01-01

A specific heterologous double-antibody radioimmunoassay has been developed to measure turkey prolactin (PRL) using a guinea pig anti-hPRL antiserum and 125 I-labelled ovine PRL [ 125 I]oPRL. Turkey pituitary prolactin and serum give parallel dose-response curves and no cross-rection is seen with turkey growth hormone, LH or FSH, or mammalian LH, FSH, TSH, GH or placental lactogens. The RIA is accurate and precise and is sufficiently sensitive to measure PRL in all physiological situations investigated in the turkey. The RIA will measure PRL in several avian species including the chicken, duck, goose, pheasant, pheasant x chicken F 1 hybrid, pigeon, quail, and rook. Plasma PRL concentrations in laying and broody turkey hens were not significantly different (46.5 +- 2.5 vs. 39.7 +- 3.8 ng/ml) but both were significantly higher (P < 0.001) than in non-laying turkey hens (4.6 +- 0.7 ng/ml). Oestradiol injection into laying hens did not alter PRL levels while the same injection in non-laying hens caused a significant three-fold increse in plasma PRL levels. (author)

Primary Hypothyroidism with Exceptionally High Prolactin-A Really Big Deal.

Science.gov (United States)

Khorassanizadeh, Rahim; Sundaresh, Vishnu; Levine, Steven N

2016-07-01

Primary hypothyroidism can cause both hyperprolactinemia and pituitary hyperplasia. The degree of hyperprolactinemia is generally modest, and rarely do prolactin concentrations exceed 100 ng/mL (4.34 nmol/L). This combination of hyperprolactinemia and pituitary gland enlargement might raise suspicion for a prolactinoma or a nonfunctioning adenoma limiting the ability of hypothalamic dopamine to inhibit prolactin production, the so-called "stalk effect." We describe a 30-year-old female with headaches, galactorrhea, and hyperprolactinemia with a presumptive diagnosis of a prolactinoma. She had hypothyroidism after treatment of Graves disease at age 17 years but was noncompliant with levothyroxine replacement. Thyroid-stimulating hormone (TSH) was 263 mIU/L, FT4 was 3.01 pmol/L, and prolactin was 323 ng/mL (14.06 nmol/L). Magnetic resonance imaging (MRI) demonstrated increased volume of the pituitary gland with homogeneous enhancement with gadolinium. Levothyroxine treatment for 2 weeks decreased her TSH to130 mIU/L, but her total prolactin remained elevated at 386 ng/mL (16.78 nmol/L). Further testing identified that 76% of the total prolactin was macroprolactin. Primary hypothyroidism can cause hyperprolactinemia, and prolonged disease may lead to pituitary hyperplasia. However, a marked elevation of prolactin should raise suspicion to investigate additional etiologies for hyperprolactinemia. Our case exemplifies a dual etiology for hyperprolactinemia and pituitary hyperplasia caused by both hypothyroidism and macroprolactin. This knowledge is invaluable for clinicians to avoid unnecessary management with dopamine agonists and/or surgery. This patient's prolactin was 323 ng/mL (14.06 nmol/L). Before our case, the highest prolactin in a hypothyroid patient reported in the literature was 253 ng/mL (11.0 nmol/L). Copyright © 2016 Elsevier Inc. All rights reserved.

EFFECT OF ADRENALECTOMY ON PROLACTIN SECRETION IN PRIMIPAROUS AND MULTIPAROUS LACTATING RATS

Directory of Open Access Journals (Sweden)

C. D. C. Sanches

2018-04-01

Full Text Available The adenohypophysis produces among other hormones prolactin, which plays an important role in reproduction, especially on the mammary glands and lactation of mammals. Prolactin is tonically controlled by tufo-infundibular dopamine, but several studies indicate that prolactin secretion is altered by the action of glucocorticoids and, therefore, is related to stress. However, the exact contribution of corticosteroids in the control of prolactin secretion is poorly understood. On the other hand, it is also known that reproductive experience can modify prolactin secretion by adenohypophysis. Thus, the present study aims to study the hormonal relationships of the hypothalamic-pituitary-adrenal axis, in particular, the glucocorticoid relationship on prolactin secretion as a function of the reproductive experience in females during lactation. The results show that reproductive experience may be a factor modifying the sensitivity of the neuroendocrine response of prolactin secretion to glucocorticoids. However, more studies are needed to understand the possible mechanisms involved, as well as possible modifications in this response as a function of the reproductive status of the females.

Atorvastatin inhibits the immediate-early response gene EGR1 and improves the functional profile of CD4+T-lymphocytes in acute coronary syndromes.

Science.gov (United States)

Severino, Anna; Zara, Chiara; Campioni, Mara; Flego, Davide; Angelini, Giulia; Pedicino, Daniela; Giglio, Ada Francesca; Trotta, Francesco; Giubilato, Simona; Pazzano, Vincenzo; Lucci, Claudia; Iaconelli, Antonio; Ruggio, Aureliano; Biasucci, Luigi Marzio; Crea, Filippo; Liuzzo, Giovanna

2017-03-14

Background- Adaptive immune-response is associated with a worse outcome in acute coronary syndromes. Statins have anti-inflammatory activity beyond lowering lipid levels. We investigated the effects of ex-vivo and in-vivo atorvastatin treatment in acute coronary syndromes on CD4+T-cells, and the underlying molecular mechanisms.Approach and results- Blood samples were collected from 50 statin-naïve acute coronary syndrome patients. We assessed CD4+T-cell activation by flow-cytometry, the expression of 84 T-helper transcription-factors and 84 T-cell related genes by RT-qPCR, and protein expression by Western-blot, before and after 24-hours incubation with increasing doses of atorvastatin: 3-10-26 μg/ml (corresponding to blood levels achieved with doses of 10-40-80 mg, respectively). After incubation, we found a significant decrease in interferon-γ-producing CD4+CD28nullT-cells (P = 0.009) and a significant increase in interleukin-10-producing CD4+CD25highT-cells (P 3-fold changes).The in-vivo effects of atorvastatin were analyzed in 10 statin-free acute coronary syndrome patients at baseline, and after 24h and 48h of atorvastatin therapy (80 mg/daily): EGR1-gene expression decreased at 24h (P = 0.01) and 48h (P = 0.005); EGR1-protein levels decreased at 48h (P = 0.03).Conclusions-In acute coronary syndromes, the effects of atorvastatin on immune system might be partially related to the inhibition of the master regulator gene EGR1. Our finding might offer a causal explanation on why statins improve the early outcome in acute coronary syndromes.

Simulation research on the effect of cooled EGR, supercharging and compression ratio on downsized SI engine knock

Science.gov (United States)

Shu, Gequn; Pan, Jiaying; Wei, Haiqiao; Shi, Ning

2013-03-01

Knock in spark-ignition(SI) engines severely limits engine performance and thermal efficiency. The researches on knock of downsized SI engine have mainly focused on structural design, performance optimization and advanced combustion modes, however there is little for simulation study on the effect of cooled exhaust gas recirculation(EGR) combined with downsizing technologies on SI engine performance. On the basis of mean pressure and oscillating pressure during combustion process, the effect of different levels of cooled EGR ratio, supercharging and compression ratio on engine dynamic and knock characteristic is researched with three-dimensional KIVA-3V program coupled with pressure wave equation. The cylinder pressure, combustion temperature, ignition delay timing, combustion duration, maximum mean pressure, and maximum oscillating pressure at different initial conditions are discussed and analyzed to investigate potential approaches to inhibiting engine knock while improving power output. The calculation results of the effect of just cooled EGR on knock characteristic show that appropriate levels of cooled EGR ratio can effectively suppress cylinder high-frequency pressure oscillations without obvious decrease in mean pressure. Analysis of the synergistic effect of cooled EGR, supercharging and compression ratio on knock characteristic indicates that under the condition of high supercharging and compression ratio, several times more cooled EGR ratio than that under the original condition is necessarily utilized to suppress knock occurrence effectively. The proposed method of synergistic effect of cooled EGR and downsizing technologies on knock characteristic, analyzed from the aspects of mean pressure and oscillating pressure, is an effective way to study downsized SI engine knock and provides knock inhibition approaches in practical engineering.

Variation in prolactin is related to variation in sexual behavior and contact affiliation.

Directory of Open Access Journals (Sweden)

Charles T Snowdon

Full Text Available Prolactin is associated with both maternal and paternal care and appears important in developing a bond between parent and infant. In contrast with oxytocin, another hormone important in infant care, there is scant information on the role of prolactin in maintaining adult heterosexual relationships. We present here the first results demonstrating a relationship between prolactin levels and sexual and contact affiliation behavior in a pair-bonded species. We studied cotton-top tamarins, a socially-monogamous, cooperatively-breeding primate. We measured chronic urinary prolactin levels over a four week period to include the entire female ovulatory cycle and correlated prolactin levels in males and females with simultaneous measures of contact affiliation and sexual behavior. Current mothers who were no longer nursing displayed lower amounts of sexual behavior and proximity than non-breeding females and also had marginally lower levels of prolactin. The prolactin levels of males and females were similar within pairs, and variation in prolactin levels for both sexes was explained both by the amount of sexual behavior and contact affiliation. The results parallel a previous study that compared oxytocin levels with sociosexual behavior in the same species, and supports the hypothesis that both prolactin and oxytocin are involved in pair-bonding as well as in infant care.

Cyclophilin B as a co-regulator of prolactin-induced gene expression and function in breast cancer cells.

Science.gov (United States)

Fang, Feng; Zheng, Jiamao; Galbaugh, Traci L; Fiorillo, Alyson A; Hjort, Elizabeth E; Zeng, Xianke; Clevenger, Charles V

2010-06-01

The effects of prolactin (PRL) during the pathogenesis of breast cancer are mediated in part though Stat5 activity enhanced by its interaction with its transcriptional inducer, the prolyl isomerase cyclophilin B (CypB). We have demonstrated that knockdown of CypB decreases cell growth, proliferation, and migration, and CypB expression is associated with malignant progression of breast cancer. In this study, we examined the effect of CypB knockdown on PRL signaling in breast cancer cells. CypB knockdown with two independent siRNAs was shown to impair PRL-induced reporter expression in breast cancer cell line. cDNA microarray analysis was performed on these cells to assess the effect of CypB reduction, and revealed a significant decrease in PRL-induced endogenous gene expression in two breast cancer cell lines. Parallel functional assays revealed corresponding alterations of both anchorage-independent cell growth and cell motility of breast cancer cells. Our results demonstrate that CypB expression levels significantly modulate PRL-induced function in breast cancer cells ultimately resulting in enhanced levels of PRL-responsive gene expression, cell growth, and migration. Given the increasingly appreciated role of PRL in the pathogenesis of breast cancer, the actions of CypB detailed here are of biological significance.

Effect of thin-film coating on wear in EGR-contaminated oil

International Nuclear Information System (INIS)

Ajayi, O. O.; Aldajah, S. H.; Erdemir, A.; Fenske, G. R.

2001-01-01

Increased use of higher-efficiency compression ignition direct injection (CIDI) diesel engines instead of today's gasoline engines will result in reduced fuel consumption and greenhouse gases emissions. However, NO(sub x) and particulate exhaust emissions from diesel engines must be significantly reduced due to their possible adverse health effects. Exhaust gas recirculation (EGR) is an effective way to reduce NO(sub x) emissions from diesel engines, but the particulates and acidic exhaust products in the recirculated gas will contaminate engine lubricant oil by increasing the soot content and total acid number (TAN). These factors will increase the wear rate in many critical engine components and seriously compromise engine durability. We have investigated the use of commercially available thin and hard coatings (TiN, TiCN, TiAlN, and CrN) to mitigate the negative effects of EGR on wear. In tests with the four-ball machine according to ASTM D4172, we found that all the four coatings deposited on M-50 steel significantly reduced wear in EGR-contaminated oils when compared with uncoated M50 steel balls

Role of engine age and lubricant chemistry on the characteristics of EGR soot

Science.gov (United States)

Adeniran, Olusanmi Adeniji

Exhaust products of Diesel Engines serves as an environmental hazard, and to curtail this problem a Tier 3 emission standard was introduced which involves change in engine designs and introduction of EGR systems in Diesel engines. EGR systems, however has the challenge of generating soot which are abrasive and are major causes of wear in Diesel engines. This work has studied the characteristics of EGR soot formed in different range of engine age and in different lubricant chemistries of Mineral and Synthetic based diesel Oils. It is found that lubricant degradation is encouraged by less efficient combustion as engine age increases, and these are precursors to formation of crystalline and amorphous particles that are causes of wear in Diesel Engines. It is found that soot from new engine is dominated by calcium based crystals which are from calcium sulfonate detergent, which reduces formation of second phase particles that can be abrasive. Diversity and peak intensity is seen to increase in soot samples as engine age increases. This understanding of second phase particles formed in engines across age ranges can help in the durability development of engine, improvement of Oil formulation for EGR engines, and in development of chemistries for after-treatment Oil solutions that can combat formation of abrasive particles in Oils.

Modulating effect of the nootropic drug, piracetam on stress- and subsequent morphine-induced prolactin secretion in male rats.

Science.gov (United States)

Matton, A.; Engelborghs, S.; Bollengier, F.; Finné, E.; Vanhaeist, L.

1996-01-01

1. The effect of the nootropic drug, piracetam on stress- and subsequent morphine-induced prolactin (PRL) secretion was investigated in vivo in male rats, by use of a stress-free blood sampling and drug administration method by means of a permanent indwelling catheter in the right jugular vein. 2. Four doses of piracetam were tested (20, 100, 200 and 400 mg kg-1), being given intraperitoneally 1 h before blood sampling; control rats received saline instead. After a first blood sample, rats were subjected to immobilization stress and received morphine, 6 mg kg-1, 90 min later. 3. Piracetam had no effect on basal plasma PRL concentration. 4. While in the non-piracetam-treated rats, stress produced a significant rise in plasma PRL concentration, in the piracetam-pretreated rats PRL peaks were attenuated, especially in the group given 100 mg kg-1 piracetam, where plasma PRL concentration was not significantly different from basal values. The dose-response relationship showed a U-shaped curve; the smallest dose had a minor inhibitory effect and the highest dose had no further effect on the PRL rise. 5. In unrestrained rats, morphine led to a significant elevation of plasma PRL concentration. After the application of immobilization stress it lost its ability to raise plasma PRL concentration in the control rats, but not in the piracetam-treated rats. This tolerance was overcome by piracetam in a significant manner but with a reversed dose-response curve; i.e. the smaller the dose of piracetam, the higher the subsequent morphine-induced PRL peak. 6. There is no simple explanation for the mechanism by which piracetam induces these contradictory effects. Interference with the excitatory amino acid system, which is also involved in opiate action, is proposed speculatively as a possible mediator of the effects of piracetam. PMID:8821540

New concept for low emission diesel combustion. 2nd Report. Combustion improvement by applying EGR and oxygenated fuel; Teikogai diesel engine no nensho concept. EGR, gansanso nenryo ni yoru nensho kaizen

Energy Technology Data Exchange (ETDEWEB)

Yokota, H.; Nakajima, H.; Kakegawa, T. [Hino Motors, Ltd., Tokyo (Japan)

1998-05-01

Described herein are performance of a new concept of premixed, multiple injection combustion, in which part of the fuel is injected into the combustion chamber at the early stage and the remainder is injected in the ordinary manner, and characteristics of the exhaust gases. Also described are the effects of EGR and oxygenated fuel on reduced HC emissions and fuel consumption. The ordinary premixed, multiple injection combustion system has problems related to fuel efficiency, and HC and particulate missions. When combined with an EGR system, this system reduces HC emissions to one-third. MTBE shows an effect of improving fuel efficiency, when mixed with diesel fuel. No particulate matter is exhausted and fuel efficiency is improved by 6%, when MTBE is present in the fuel at 30% by weight. The pre-mixture is less homogeneous in the absence of EGR and oxygenated fuel, producing a luminous flame observed in the fuel-rich region. No such a flame is observed, when MTBE is added to the fuel and suction air temperature is increased to the level corresponding to that associated with EGR, conceivably resulting from increased suction air temperature and lower boiling point of MTBE, which together make the pre-mixture leaner and more homogeneous. 7 refs., 9 figs., 2 tabs.

Effects of ovarian steroids and prolactin on the sequential development of nesting behaviour in female budgerigars.

Science.gov (United States)

Hutchison, R E

1975-10-01

As intact, breeding female budgerigars approach egg-laying, they spend an increasing amount of time in the nestbox and nest hollow. The brood patch area begins to defeather and becomes vascular and the oviduct increases in weight. Precursory albumen forms in the tubular glands of the oviduct. Oestradiol (OB) treatment in combination with prolactin (OB+PL) induced ovariectomized budgerigars to display nesting behaviour which did not differ from that shown by intact females in the 3 days immediately preceding egg-laying. In contrast, OB induced only the initial phase of the nesting sequence and the effects of OB in combination with progesterone (OB+PR) were intermediate between treatments with OB alone and OB+PL. Incubation of artificial eggs occurred only in the OB+PL group and the latency to display of the incubation posture was shorter in the OB+PL group than in the OB+PR group. No incubation posture was displayed by the OB-treated group. Oviduct development was not influenced by prolactin, but progesterone induced precocious development of tubular glands in the magnum region of the oviduct. Treatment with OB+PR induced uniform development of precursor albumen in the tubular glands. Development of the brood patch occurred with both OB+PL and OB+PR treatment. However, OB+PR resulted in defeathering which was advanced in relation to vascularity when compared with intact breeding females, whereas defeathering and vascularity of the OB+PL group did not differ from that of intact females at egg-laying. These results indicate that prolactin in combination with oestradiol was more effective than progesterone not only in inducing the later phases of nesting behaviour but also in initiating incubation behaviour and defeathering of the brood patch area.

A homologous radioimmunoassay for canine prolactin: plasma levels huring the reproductive cycle

International Nuclear Information System (INIS)

Coster, R. De; Beerens, D.; Mey, J. De; Beckers, J.-F.

1983-01-01

A method is described for the purification of canine prolactin, involving preparative isoelectrofocusing. Canine prolactin has a molecular weight of 23 000 daltons, an isoelectric point of 5.7 and exhibits a high degree of homogeneity in polyacrylamide gels stained by means of a silver method. A specific, homologous radioimmunoassay is described using the Bolton-Hunter method for preparation of the labelled ligand, with a sensitivity of 0.1 ng/tube. Basal plasma prolactin levels of 2-4 ng/ml obtained through the oestrous cycle remained fairly constant but a rise of 9 ng/ml was found at the end of dioestrus in non-pregnant bitches. Level also rose 30 days after mating to reach a peak of about 50 ng/ml near parturition and during early lactation. (author)

Development of High Efficiency and Low Emission Low Temperature Combustion Diesel Engine with Direct EGR Injection

Science.gov (United States)

Ho, R. J.; Kumaran, P.; Yusoff, M. Z.

2016-03-01

Focus on energy and environmental sustainability policy has put automotive research & development directed to developing high efficiency and low pollutant power train. Diffused flame controlled diesel combustion has reach its limitation and has driven R&D to explore other modes of combustions. Known effective mode of combustion to reduce emission are Low temperature combustion (LTC) and homogeneous charge combustion ignition by suppressing Nitrogen Oxide(NOx) and Particulate Matter (PM) formation. The key control to meet this requirement are chemical composition and distribution of fuel and gas during a combustion process. Most research to accomplish this goal is done by manipulating injected mass flow rate and varying indirect EGR through intake manifold. This research paper shows viable alternative direct combustion control via co-axial direct EGR injection with fuel injection process. A simulation study with OpenFOAM is conducted by varying EGR injection velocity and direct EGR injector diameter performed with under two conditions with non-combustion and combustion. n-heptane (C7H16) is used as surrogate fuel together with 57 species 290 semi-detailed chemical kinetic model developed by Chalmers University is used for combustion simulation. Simulation result indicates viability of co-axial EGR injection as a method for low temperature combustion control.

Evaluation of prolactin levels in patients with newly diagnosed pemphigus vulgaris and its correlation with pemphigus disease area index.

Science.gov (United States)

Lajevardi, Vahideh; Hallaji, Zahra; Daneshpazhooh, Maryam; Ghandi, Narges; Shekari, Peyman; Khani, Sepideh

2016-06-01

Prolactin is a hormone; in addition to it known roles, it has immunomodulatory effects on lymphocytes maturation and immunoglobulins production. Hyperprolactinemia has been demonstrated in various autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, type I diabetes mellitus, and Graves' disease. In view of the prolactin immunomodulatory roles, studying prolactin levels in pemphigus as an autoimmune blistering disease may introduce new ways of understanding disease etiology and developing treatment strategies. Our purpose was to determine the prolactin levels in patients with newly diagnosed pemphigus vulgaris and study its correlation with pemphigus disease area index. Our study was limited by the lack of a control group. In this cross-sectional study, prolactin and anti-desmoglein 1 and 3 autoantibodies levels were measured in 50 patients with newly diagnosed pemphigus vulgaris in Razi Dermatology Hospital. Pemphigus severity and extent was estimated using the Pemphigus Disease Area Index. Of the 50 patients, 18 were male and 32 were female with a mean age of 41.56 ± 13.66 years. Mean prolactin (PRL) level was 15.60 ± 11.72 ng/ml (10.68 in males and 18.37 in females). Mean anti-desmoglein 1 and 3 autoantibodies were 135.8 ± 119.8 and 245.8 ± 157.4 U/ml, respectively. Eleven out of 50 patients had a higher than normal prolactin range. No relation was found between prolactin level and disease activity ( p = .982). Also, correlation studies show no relation between prolactin and anti-desmoglein 1 and 3 autoantibodies levels (respectively, p = .771 and .738). In comparing the extent of the disease between the two groups with normal and high prolactin, paired t-test showed no significance ( p = .204). In our study, 22% of patients had hyperprolactinemia, which was greater among females. The highest PRL level was detected in mucocutaneous group. Although serum PRL levels were higher in patients with a greater Pemphigus Disease Area Index

Correlation between FSH, LH and prolactin serum levels. [Radioimmunoassay of hormones

Energy Technology Data Exchange (ETDEWEB)

Krause, W [Giessen Univ. (Germany, F.R.)

1978-01-01

In 188 males FSH, LH, and prolactin serum levels determined by radioimmunoassay from a single blood sample were found to be closely correlated. No correlation appeared to testosterone levels. The same correlation is observed, if serum levels of FSH, LH, and prolactin are measured after stimulation with LH-RH and TRH. In order to explain the close correlation, in five young men hormone levels were measured at 2-min-intervals over a period of 2 hours. Peaks of prolactin often correspond to those of FSH and LH, and a statistical correlation was found in two cases between FSH and prolactin. Results suggest a common releasing mechanism, which is superposed to the main mediating mechanism.

Application of an EGR system in a direct injection diesel engine to reduce NOx emissions

Science.gov (United States)

De Serio, D.; De Oliveira, A.; Sodré, J. R.

2016-09-01

This work presents the application of an exhaust gas recirculation (EGR) system in a direct injection diesel engine operating with diesel oil containing 7% biodiesel (B7). EGR rates of up to 10% were applied with the primary aim to reduce oxides of nitrogen (NOx) emissions. The experiments were conducted in a 44 kW diesel power generator to evaluate engine performance and emissions for different load settings. The use of EGR caused a peak pressure reduction during the combustion process and a decrease in thermal efficiency, mainly at high engine loads. A reduction of NOx emissions of up to 26% was achieved, though penalizing carbon monoxide (CO) and total hydrocarbons (THC) emissions.

Prolactin promotes breast cancer cell migration through actin cytoskeleton remodeling

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Priscilla Ludovico da Silva

2015-12-01

Full Text Available The role of prolactin on breast cancer development and progression is debated. Breast cancer progression largely depends on cell movement and on the ability to remodel the actin cytoskeleton. In this process, actin-binding proteins are requested to achieve fibrillar actin de-polymerization and relocation at the cell membrane. Kinases such as focal adhesion kinase (FAK are later required to form actin/vinculin-enriched structures called focal adhesion complexes, which mediate firm adhesion to the extracellular matrix. These controllers are regulated by c-Src, which forms multiprotein signaling complexes with membrane receptors and is regulated by a number of hormones, including prolactin. We here show that breast cancer cells exposed to prolactin display an elevated c-Src expression and phosphorylation. In parallel, increased moesin and FAK expression and phosphorylation are found. These molecular changes are associated to relocation to the plasma membrane of cytoskeletal actin fibers and to increased horizontal cell movement. In conclusion, prolactin regulates actin remodeling and enhances breast cancer cell movement. This finding broadens the understanding of prolactin actions on breast cancer cells, highlighting new pathways that may be relevant to on breast cancer progression.

Expression of immediate-early genes in the inferior colliculus and auditory cortex in salicylate-induced tinnitus in rat.

Science.gov (United States)

Hu, S S; Mei, L; Chen, J Y; Huang, Z W; Wu, H

2014-03-12

Tinnitus could be associated with neuronal hyperactivity in the auditory center. As a neuronal activity marker, immediate-early gene (IEG) expression is considered part of a general neuronal response to natural stimuli. Some IEGs, especially the activity-dependent cytoskeletal protein (Arc) and the early growth response gene-1 (Egr-1), appear to be highly correlated with sensory-evoked neuronal activity. We hypothesize, therefore, an increase of Arc and Egr-1 will be observed in a tinnitus model. In our study, we used the gap prepulse inhibition of acoustic startle (GPIAS) paradigm to confirm that salicylate induces tinnitus-like behavior in rats. However, expression of the Arc gene and Egr-1 gene were decreased in the inferior colliculus (IC) and auditory cortex (AC), in contradiction of our hypothesis. Expression of N-methyl d-aspartate receptor subunit 2B (NR2B) was increased and all of these changes returned to normal 14 days after treatment with salicylate ceased. These data revealed long-time administration of salicylate induced tinnitus markedly but reversibly and caused neural plasticity changes in the IC and the AC. Decreased expression of Arc and Egr-1 might be involved with instability of synaptic plasticity in tinnitus.

Prolactin and Dehydroepiandrosterone Levels in Women with Systemic Lupus Erythematosus: The Role of the Extrapituitary Prolactin Promoter Polymorphism at −1149G/T

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Edward L. Treadwell

2015-01-01

Full Text Available Systemic lupus erythematosus (SLE has shown an association with high levels of prolactin, low levels of dehydroepiandrosterone (DHEA, and induction of inflammatory cytokines in the serum of patients with the disease. This preliminary study examined the relevance of a −1149G/T functional single-nucleotide polymorphism (SNP (rs1341239 in the promoter of the extrapituitary prolactin gene in a cohort of African American and European American women with lupus. Examination of this SNP revealed that the −1149TT genotype was correlated with higher levels of prolactin in serum and prolactin gene expression (p=0.0001 in peripheral blood mononuclear cells (PBMCs. Lower levels of DHEA in serum were demonstrated in lupus patients (p=0.001; those with the −1149TT genotype had the lowest levels of DHEA. Furthermore, a small subset of women who were on DHEA therapy and had a TT genotype showed a significant decrease in prolactin gene expression and lower disease activity scores (SLEDAI. Lupus patients, particularly African Americans, had significantly higher levels of IL-6 (p=0.0001 and TNF-α (p=0.042. This study suggests that the −1149TT genotype may be a risk factor for lupus and may predict who could possibly benefit from DHEA therapy; therefore, these results should be validated in a larger cohort with all ethnic groups.

Cannabidivarin (CBDV suppresses pentylenetetrazole (PTZ-induced increases in epilepsy-related gene expression

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Naoki Amada

2013-11-01

Full Text Available To date, anticonvulsant effects of the plant cannabinoid, cannabidivarin (CBDV, have been reported in several animal models of seizure. However, these behaviourally observed anticonvulsant effects have not been confirmed at the molecular level. To examine changes to epilepsy-related gene expression following chemical convulsant treatment and their subsequent control by phytocannabinoid administration, we behaviourally evaluated effects of CBDV (400 mg/kg, p.o. on acute, pentylenetetrazole (PTZ: 95 mg/kg, i.p.-induced seizures, quantified expression levels of several epilepsy-related genes (Fos, Casp 3, Ccl3, Ccl4, Npy, Arc, Penk, Camk2a, Bdnf and Egr1 by qPCR using hippocampal, neocortical and prefrontal cortical tissue samples before examining correlations between expression changes and seizure severity. PTZ treatment alone produced generalised seizures (median: 5.00 and significantly increased expression of Fos, Egr1, Arc, Ccl4 and Bdnf. Consistent with previous findings, CBDV significantly decreased PTZ-induced seizure severity (median: 3.25 and increased latency to the first sign of seizure. Furthermore, there were correlations between reductions of seizure severity and mRNA expression of Fos, Egr1, Arc, Ccl4 and Bdnf in the majority of brain regions in the CBDV+PTZ treated group. When CBDV treated animals were grouped into CBDV responders (criterion: seizure severity ≤3.25 and non-responders (criterion: seizure severity >3.25, PTZ-induced increases of Fos, Egr1, Arc, Ccl4 and Bdnf expression were suppressed in CBDV responders. These results provide the first molecular confirmation of behaviourally observed effects of the non-psychoactive, anticonvulsant cannabinoid, CBDV, upon chemically-induced seizures and serve to underscore its suitability for clinical development.

Lack of effect of naloxone on prolactin and seizures in electroconvulsive therapy.

Science.gov (United States)

Sperling, M R; Melmed, S; McAllister, T; Price, T R

1989-01-01

Both opiate agonist and antagonist injection have been reported to modulate prolactin secretion, alter brain excitability and produce seizures, and modify the postictal state. We studied the effects of administration of high-dose naloxone, an opiate antagonist, on postictal prolactin levels, seizure duration, and postictal behavior, using patients undergoing electroconvulsive therapy (ECT) as a seizure model. Seven patients had 8 mg naloxone injected prior to one ECT treatment and saline injected prior to another treatment, with the order of injection randomized. Before ECT and 15 min after ECT, prolactin levels were drawn, and no blunting of the expected postictal prolactin elevation by naloxone injection was observed. We found no evidence that endogenous opiates trigger prolactin secretion during seizures. Seizure duration was also similar in saline and naloxone groups, and naloxone did not reverse postictal depression, as has been reported in an animal model.

Elevated levels of mitochonrial respiratory complexes activities and ATP production in 17-β-estradiol-induced prolactin-secretory tumor cells in male rats are inhibited by melatonin in vivo and in vitro.

Science.gov (United States)

Wang, Bao-Qiang; Yang, Quan-Hui; Xu, Rong-Kun; Xu, Jian-Ning

2013-01-01

Our earlier studies indicate that melatonin inhibits the proliferation of prolactinoma and induces apoptosis of pituitary prolactin-secreting tumor in rats. Melatonin has also been shown to induce apoptosis and to reduce the production of ATP in breast tumor cells. This study analyzed the levels of the four mitochondrial respiratory complexes and the production of ATP and also the effects of melatonin treatment of prolactinoma. In the in vivo study, mitochondria were harvested from control pituitaries or prolactinoma collected from the pituitaries of melatonin- and 17-β-estradiol (E2)-treated male rats. In the in vitro study, prolactinoma cells mitochondria were harvested. Activities of the four mitochondrial respiratory complexes were assayed using fluorometer. ATP production of prolactinoma cells was estimated using bioluminescent methods. Elevated levels of four mitochondrial respiratory complexes activities and ATP production were recorded in prolactinoma cells. Moreover, in both in vivo and in vitro studies, melatonin inhibited the activities of mitochondrial respiratory complexes and the production of ATP in prolactinoma cells. There is a link between mitochondrial function increase and tumorigenesis. Melatonin induces apoptosis of pituitary prolactin-secreting tumor of rats via the induction of mitochondrial dysfunction and inhibition of energy metabolism.

Effect of Changes in Prolactin RIA Reactants on the Validity of the Results

International Nuclear Information System (INIS)

Ahmed, A.M.; Megahed, Y.M.; El Mosallamy, M.A.F.; El-Khoshnia, R.A.M.

1998-01-01

Human prolactin plays an essential role in the secretion of milk and has the ability to suppress gonadal function. This study is considered as atrial to discuss some technical problems which made by operator in the RIA technique to select an optimized reliable and valid parameters for the measurement of prolactin concentration in human sera. Prolactin concentration was measured in normal control group and chronic renal failure group using the optimized technique. Finally the present optimized technique is very suitable selected one for measurement of prolactin

On the Computation of Turbulent Mixing Processes with Application to EGR in IC-engines

OpenAIRE

Sakowitz, Alexander

2011-01-01

This thesis deals with turbulent mixing processes occuring in internal combustion engines, when applying exhaust gas recirculation (EGR). EGR is a very efficient way to reduce emissions of nitrogen oxides (NOx) in internal combustion engines. Exhaust gases are recirculated and mixed with the intake air of the engine, thus reducing the oxygen concentration of the combustion gas and the maximum combustion tempera- ture. This temperature decrease results in a reduction of NOx emissions, since NO...

Effects of port fuel injection (PFI) of n-butanol and EGR on combustion and emissions of a direct injection diesel engine

International Nuclear Information System (INIS)

Chen, Zheng; Liu, Jingping; Wu, Zhenkuo; Lee, Chiafon

2013-01-01

Highlights: • A DI diesel engine with PFI of n-butanol in combination with EGR is investigated. • Butanol concentration and EGR have a coupled impact on combustion process. • A combination of butanol PFI and EGR can break through tradeoff between NOx and soot. • DI diesel with butanol PFI has lower ITE than DI of diesel–butanol blends. - Abstract: An experimental investigation was conducted on a direct injection (DI) diesel engine with exhaust gas recirculation (EGR), coupled with port fuel injection (PFI) of n-butanol. Effects of butanol concentration and EGR rate on combustion, efficiency, and emissions of the tested engine were evaluated, and also compared to a DI mode of diesel–butanol blended fuel. The results show butanol concentration and EGR rate have a coupled impact on combustion process. Under low EGR rate condition, both the peak cylinder pressure and the peak heat release rate increase with increased butanol concentration, but no visible influence was found on the ignition delay. Under high EGR rate condition, however, the peak cylinder pressure and the peak heat release rate both decrease with increased butanol concentration, accompanied by longer ignition delay and longer combustion duration. As regard to the regulated emissions, HC and CO emissions increase with increased butanol concentration, causing higher indicated specific fuel consumption (ISFC) and lower indicated thermal efficiency (ITE). It is also noted that butanol PFI in combination with EGR can change the trade-off relationship between NOx and soot, and simultaneously reduce both into a very low level. Compared with the DI mode of diesel–butanol blended fuel, however, the DI diesel engine with butanol PFI has higher HC and CO emissions and lower ITE. Therefore, future research should be focused on overcoming the identified shortcomings by an improved injection strategy of butanol PFI

Exhaust Aftertreatment and Low Pressure Loop EGR Applied to an Off-Highway Engine

Energy Technology Data Exchange (ETDEWEB)

Baumgard, Kirby; Triana, Antonio; Johnson, John; Yang, Song; Premchand, Kiran

2006-01-30

The goal of the project was to demonstrate that low pressure loop EGR incorporating a diesel oxidation catalyst (DOC) and a diesel particulate filter (DPF) can be applied to an off-highway engine to meet Tier 3 (Task I) and Interim Tier 4 (Task II) off-road emissions standards. Task I data was collected using a John Deere 8.1 liter engine modified with a low pressure loop EGR system. The engine and EGR system was optimized and final data over the ISO 8178 eight mode test indicated the NOx emissions were less than 4 g/kWh and the PM was less than 0.02 g/kWh which means the engine met the Tier 3 off-road standard. Considerable experimental data was collected and used by Michigan Tech University to develop and calibrate the MTU-Filter 1D DPF model. The MTU-Filter 1D DPF code predicts the particulate mass evolution (deposition and oxidation) in the diesel particulate filter (DPF) during simultaneous loading and during thermal and NO{sub 2}-assisted regeneration conditions. It also predicts the pressure drop across the DPF, the flow and temperature fields, the solid filtration efficiency and the particle number distribution downstream of the DPF. A DOC model was also used to predict the NO{sub 2} upstream of the DPF. The DPF model was calibrated to the experimental data at temperatures from 230 C to 550 C, and volumetric flow rates from 9 to 39 actual m{sup 3}/min. Model predictions of the solid particulate mass deposited in the DPF after each loading and regeneration case were in agreement within +/-10g (or +/-10%) of experimental measurements at the majority of the engine operating conditions. The activation temperatures obtained from the model calibration are in good agreement with values reported in the literature and gave good results in the model calibration by using constant pre-exponential factors throughout the entire range of conditions evaluated. The average clean filter permeability was 2.372 x 10{sup -13} m{sup 2}. Estimates of the solid particulate mass

Polymorphism of the prolactin gene and its association with egg ...

African Journals Online (AJOL)

p2492989

In this study, polymorphism of the prolactin gene was screened in six Chinese native ... Prolactin (PRL) is a single-chain polypeptide hormone that belongs to the growth hormone gene ..... Enhance the efficiency of single-strand conformation polymorphism analysis by short polyacrylamide gel and modified silver staining.

Mammalian Prolactin – An Ancient But Still A Mysterious Hormone

Indian Academy of Sciences (India)

Table of contents. Mammalian Prolactin – An Ancient But Still A Mysterious Hormone · Prolactin inhibits LHRH action during lactational ammenorrhoea · Slide 3 · Slide 4 · REDUCTIONIST VIEW OF HORMONES · CONCERN · PURIFICATION PROTOCOLS · CHARACTERIZATION OF HORMONES · Slide 9 · Slide 10.

Adjunctive treatment with aripiprazole for risperidone-induced hyperprolactinemia

Directory of Open Access Journals (Sweden)

Ranjbar F

2015-03-01

Full Text Available Fatemeh Ranjbar,1 Homayoun Sadeghi-Bazargani,2,3 Parisa Niari Khams,1 Asghar Arfaie,1 Azim Salari,4 Mostafa Farahbakhsh1 1Clinical Psychiatry Research Center, Tabriz University of Medical Sciences, Tabriz, East Azerbaijan, Iran; 2Road Traffic Injury Research Center, Department of Statistics & Epidemiology, Tabriz University of Medical Sciences, Tabriz, Iran; 3World Health Organization Collaborating Center on Community Safety Promotion, Karolinska Institute, Stockholm, Sweden; 4Emam Khomeini Hospital, Naghadeh, West Azerbaijan, Iran Background: Antipsychotics have been used for more than 50 years in the treatment of schizophrenia and many other psychiatric disorders. Prolactin levels usually increase in patients treated with risperidone. Aripiprazole, which has a unique effect as an antipsychotic, is a D2 receptor partial agonist. It is an atypical antipsychotic with limited extrapyramidal symptoms. Since it acts as an antagonist in hyperdopaminergic conditions and as an agonist in hypodopaminergic conditions, it does not have adverse effects on serum prolactin levels. The present study aimed to investigate the effect of aripiprazole on risperidone-induced hyperprolactinemia. Methods: This before-and-after clinical trial was performed in 30 patients. Baseline prolactin levels were measured in all patients who were candidates for treatment with risperidone. In subjects with elevated serum prolactin, aripiprazole was added to their treatment. Serum prolactin levels were measured during the first week, second week, and monthly thereafter for at least 3 months or until prolactin levels became normal. The data were analyzed using Stata version 11 software. Survival analysis and McNemar’s test were also performed. Results: The mean age of the participants was 30.8 years. Prolactin levels normalized in 23 (77% participants during the study, and menstrual disturbances normalized in 25 (83.3%. Prolactin levels normalized in most patients between days 50

The characterization of DNA methylation-mediated regulation of bovine placental lactogen and bovine prolactin-related protein-1 genes

Directory of Open Access Journals (Sweden)

Patel Osman V

2009-03-01

Full Text Available Abstract Background Bovine trophoblast binucleate cells (BNC express a plethora of molecules including bovine placental lactogen (bPL, gene name is bCSH1 and bovine prolactin-related protein-1 (bPRP1. BCSH1 and bPRP1 are members of the growth hormone (GH/prolactin (PRL gene family, which are expressed simultaneously in BNC and are central to placentation and the progression of pregnancy in cattle. However, there is a paucity of information on the transcriptional regulatory mechanisms of both the bCSH1 and bPRP1 genes. Recent studies, however, have demonstrated that the expression of a number of genes is controlled by the methylation status of their promoter region. In the present study, we examined the cell-type-specific epigenetic alterations of the 5'-flanking region of the bCSH1 and bPRP1 genes to gain an insight into their regulatory mechanisms. Results Analysis of 5-aza-2'-deoxycytidine treatment demonstrated that bCSH1 expression is moderately induced in fibroblast cultures but enhanced in BT-1 cells. Sodium bisulfite based sequencing revealed that bCSH1 is hypomethylated in the cotyledonary tissue but not in the fetal skin, and this pattern was not altered with the progression of pregnancy. On the other hand, the methylation status of bPRP1 was similar between the cotyledon and fetal skin. The bPRP1 gene was exclusively hypermethylated in a bovine trophoblast cell-derived BT-1 cell-line. While the activity of bCSH1 was similar in both BT-1 and bovine fibroblast cells, that of bPRP1 was specific to BT-1. Treatment with a demethylating agent and luciferase assays provided in vitro evidence of the positive regulation of bCSH1 but not bPRP1. Conclusion This is the first report to identify the differential regulatory mechanisms of the bCSH1 and bPRP1 genes and indicates that bCSH1 might potentially be the only transcript that is subject to DNA methyltransferase regulation. The data indicates the possibility of novel kinetics of induction of

Effect of THIP and SL 76002, two clinically experimented GABA-mimetic compounds, on anterior pituitary GABA receptors and prolactin secretion in the rat

International Nuclear Information System (INIS)

Apud, J.A.; Masotto, C.; Racagni, G.

1987-01-01

In the present study, the ability of three direct GABA agonists, muscimol, THIP and SL 76002 to displace 3 H-GABA binding from anterior pituitary and medio-basal hypothalamus membranes was evaluated. Further, the effect of both THIP and SL 76002 on baseline prolactin levels or after stimulation of hormone release with haloperidol has been also studied. Either muscimol, THIP or SL 76002 have shown to posses 7-, 7- and 3-fold higher affinity, respectively, for the central nervous system than for the anterior pituitary 3 H-GABA binding sites. Moreover, THIP and SL 76002 have demonstrated to be respectively, 25- and 1000- fold less potent than muscimol in inhibiting 3 H- GABA binding at the level of the anterior pituitary and about 25- and 2700-fold less potent at the level of the medio-basal hypothalamus. Under basal conditions, either THIP or SL 76002 were ineffective to reduce prolactin release. However, after stimulation of prolactin secretion through blockade of the dopaminergic neurotransmission with haloperidol (0.1 mg/kg), both THIP (10 mg/kg) and SL 76002 (200 mg/kg) significantly counteracted the neuroleptic-induced prolactin rise with a potency which is in line with their ability to inhibit 3 H-GABA binding in the anterior pituitary. The present results indicate that both compounds inhibit prolactin release under specific experimental situations probably through a GABAergic mechanism. In view of the endocrine effects of these GABA-mimetic compounds, the possibility arises for an application of these type of drugs in clinical neuroendocrinology. 35 references, 3 figures, 2 tables

From Bench to Bedside: Translating the Prolactin/Vasoinhibin Axis

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Jakob Triebel

2017-12-01

Full Text Available The prolactin/vasoinhibin axis defines an endocrine system, in which prolactin (PRL and vasoinhibins regulate blood vessel growth and function, the secretion of other hormones, inflammatory and immune processes, coagulation, and behavior. The core element of the PRL/vasoinhibin axis is the generation of vasoinhibins, which consists in the proteolytic cleavage of their precursor molecule PRL. Vasoinhibins can interact with multiple different partners to mediate their effects in various tissues and anatomical compartments, indicating their pleiotropic nature. Based on accumulating knowledge about the PRL/vasoinhibin axis, two clinical trials were initiated, in which vasoinhibin levels are the target of therapeutic interventions. One trial investigates the effect of levosulpiride, a selective dopamine D2-receptor antagonist, on retinal alterations in patients with diabetic macular edema and retinopathy. The rationale of this trial is that the levosulpiride-induced hyperprolactinemia resulting in increased retinal vasoinhibins could lead to beneficiary outcomes in terms of a vasoinhibin-mediated antagonization of diabetes-induced retinal alterations. Another trial investigated the effect of bromocriptine, a dopamine D2-receptor agonist, for the treatment of peripartum cardiomyopathy. The rationale of treatment with bromocriptine is the inhibition of vasoinhibin generation by substrate depletion to prevent detrimental effects on the myocardial microvascularization. The trial demonstrated that bromocriptine treatment was associated with a high rate of left ventricular recovery and low morbidity and mortality. Therapeutic interventions into the PRL/vasoinhibin axis bear the risk of side effects in the areas of blood coagulation, blood pressure, and alterations of the mental state.

ATM Is Required for the Prolactin-Induced HSP90-Mediated Increase in Cellular Viability and Clonogenic Growth After DNA Damage.

Science.gov (United States)

Karayazi Atici, Ödül; Urbanska, Anna; Gopinathan, Sesha Gopal; Boutillon, Florence; Goffin, Vincent; Shemanko, Carrie S

2018-02-01

Prolactin (PRL) acts as a survival factor for breast cancer cells, but the PRL signaling pathway and the mechanism are unknown. Previously, we identified the master chaperone, heat shock protein 90 (HSP90) α, as a prolactin-Janus kinase 2 (JAK2)-signal transducer and activator of transcription 5 (STAT5) target gene involved in survival, and here we investigated the role of HSP90 in the mechanism of PRL-induced viability in response to DNA damage. The ataxia-telangiectasia mutated kinase (ATM) protein plays a critical role in the cellular response to double-strand DNA damage. We observed that PRL increased viability of breast cancer cells treated with doxorubicin or etoposide. The increase in cellular resistance is specific to the PRL receptor, because the PRL receptor antagonist, Δ1-9-G129R-hPRL, prevented the increase in viability. Two different HSP90 inhibitors, 17-allylamino-17-demethoxygeldanamycin and BIIB021, reduced the PRL-mediated increase in cell viability of doxorubicin-treated cells and led to a decrease in JAK2, ATM, and phosphorylated ATM protein levels. Inhibitors of JAK2 (G6) and ATM (KU55933) abolished the PRL-mediated increase in cell viability of DNA-damaged cells, supporting the involvement of each, as well as the crosstalk of ATM with the PRL pathway in the context of DNA damage. Drug synergism was detected between the ATM inhibitor (KU55933) and doxorubicin and between the HSP90 inhibitor (BIIB021) and doxorubicin. Short interfering RNA directed against ATM prevented the PRL-mediated increase in cell survival in two-dimensional cell culture, three-dimensional collagen gel cultures, and clonogenic cell survival, after doxorubicin treatment. Our results indicate that ATM contributes to the PRL-JAK2-STAT5-HSP90 pathway in mediating cellular resistance to DNA-damaging agents. Copyright © 2018 Endocrine Society.

Agnus castus extracts inhibit prolactin secretion of rat pituitary cells.

Science.gov (United States)

Sliutz, G; Speiser, P; Schultz, A M; Spona, J; Zeillinger, R

1993-05-01

In our studies on prolactin inhibition by plant extracts we focused on the effects of extracts of Vitex agnus castus and its preparations on rat pituitary cells under basal and stimulated conditions in primary cell culture. Both extracts from Vitex agnus castus as well as synthetic dopamine agonists (Lisuride) significantly inhibit basal as well as TRH-stimulated prolactin secretion of rat pituitary cells in vitro and as a consequence inhibition of prolactin secretion could be blocked by adding a dopamine receptor blocker. Therefore because of its dopaminergic effect Agnus castus could be considered as an efficient alternative phytotherapeutic drug in the treatment of slight hyperprolactinaemia.

RELATIONSHIP BETWEEN PROLACTIN HORMONE LEVEL, MOLTING AND DUCK EGG PRODUCTION

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T. Susanti

2012-09-01

Full Text Available The aims of this study were to obtain information on the mechanism of molting and the prolactin hormone levels affecting egg production. The study utilized AP (crossbred of Alabio ♂ with Peking ♀ and PA (crossbred of Peking ♂ and Alabio ♀ ducks with a total of 180 birds. The observed variables were the duration of cessation of egg production before and after molting, the prolactin hormone level in the period of molting, the egg production period before and after molting. The data was analyzed using ANOVA, regression and correlation. The results showed that AP crossbred had fewer molting (23.33% compared to PA (50.00%. The mechanism of molting is always preceded by cessation of egg production, molting and relaying. The prolactin hormone concentrations of AP and PA in the period before and after molting were significantly higher than in the period of molting. At the egg production period before molting, the prolactin hormone concentration of AP ducks was higher than the PA ducks. So that the egg production of AP before molting (0-16 weeks was higher than the PA. The egg production of AP was higher than PA, 256.66±6.00 vs 232.22±6.64 eggs for 48 weeks. So it can be concluded that the prolactin hormone affects the molting and egg production.

Obtention of antibodies anti prolactin from human prolactin of national production; Obtencion de anticuerpos anti-prolactina a partir de prolactina humana de produccion nacional

Energy Technology Data Exchange (ETDEWEB)

Caso, R; Mosquera, M [Centro de Isotopos, La Habana (Cuba); Perez, E [Centro de Investigaciones de Mejoramiento Animal, La Habana (Cuba); Amanz, C [Instituto Nacional de Endocrinologia, La Habana (Cuba)

1996-07-01

In this work was studied the use of the the Prolactin hormone as immuno gen, which is obtained in Cuba by the pharmaceutical institute Mario Munoz, to produce the antibody antiprolactin. Was made the validation of obtained antibody (tritatium, specificity and affinity) The produced antibody had necessary quality to be use as a component of the Kits-RIA Prolactin.

ACTIONS OF PROLACTIN IN THE BRAIN: FROM PHYSIOLOGICAL ADAPTATIONS TO STRESS AND NEUROGENESIS TO PSYCHOPATHOLOGY

Directory of Open Access Journals (Sweden)

Luz eTorner

2016-03-01

Full Text Available Prolactin is one of the most versatile hormones known. It is considered an adaptive hormone due to the key roles it plays in the modulation of the stress response and during pregnancy and lactation. Within the brain, prolactin acts as a neuropeptide to promote physiological responses related to reproduction, stress adaptation, neurogenesis, and neuroprotection. The action of prolactin on the nervous system contributes to the wide array of changes that occur in the female brain during pregnancy and result in the attenuation of the hypothalamic pituitary adrenal axis. Together, all these changes promote behavioral and physiological adaptations of the new mother to enable reproductive success. Brain adaptations driven by prolactin are also important for the regulation of maternal emotionality and wellbeing Prolactin also affects the male brain during the stress response but its effects have been less studied. Prolactin regulates neurogenesis both in the subventricular zone and in the hippocampus. Therefore, alterations in the prolactin system due to stress, or exposure to substances that reduce neurogenesis or other conditions, could contribute to maladaptive responses and pathological behavioral outcomes. Here we review the prolactin system and the role it plays in the modulation of stress response and emotion regulation. We discuss the effects of prolactin on neurogenesis and neuroprotection, the putative neuronal mechanisms underlying these effects, and their contribution to the onset of psychopathological states like depression.

Comparative study in LTC Combustion between a short HP EGR loop without cooler and a variable lift and duration system

Energy Technology Data Exchange (ETDEWEB)

Bression, Guillaume; Pacaud, Pierre; Soleri, Dominique; Cessou, Jerome [IFP (France); Azoulay, David [Renault Powertrain Div. (France); Lawrence, David [Mechadyne (United Kingdom); Doradoux, Laurent; Guerrassi, Noureddine [Delphi Diesel Systems (France)

2008-07-01

In order to reach future Diesel emission standards such as Euro 6 or Tier 2 Bin 5, NO{sub x} emissions need to be dramatically reduced. Advanced technologies and engine settings such as higher EGR rates, reduced compression ratio, EGR cooler and low-pressure EGR loop - depending on vehicle application - may help to reach this target whilst maintaining low CO{sub 2} emissions and fuel consumption. However, the resulting low combustion temperatures and the low air-fuel ratios lead to a significant increase in HC and CO emissions, especially during the start-up phase prior to catalyst light-off. Moreover, high levels of EGR make transient operation even more difficult. So HC-CO emissions and EGR transient operation represent two key issues that could limit the extension of this alternative combustion mode. Consequently, an in-depth investigation of a variable lift and duration (VLD) system was performed to overcome these problems on a 4-cylinder engine, which was also equipped with a dual HP-LP EGR loop. The VLD system tested in this paper produces a variable camshaft-operated exhaust valve re-opening, which is controlled by a hydraulic rotary actuator, ensuring quick and accurate regulation of the internal gas recirculation (IGR). By increasing gas temperature in the combustion chamber, this advanced technology allows us to reduce HC-CO emissions by 50% under 3 bar BMEP. Although efficient, this technology has to be compared with other solutions from a cost-to-value point of view. The aim of this paper is firstly to compare the double lift exhaust system with a short route high-performance EGR loop without cooler by quantifying their respective gains on steady state points of the NEDC cycle, then by evaluating their potential performances during transient conditions. With the short-route EGR, the potential in HC-CO emission reduction remains significant on a large scale of engine temperatures representative of engine warm up. However, the VLD system allows us to

A comparison between EGR and lean-burn strategies employed in a natural gas SI engine using a two-zone combustion model

Energy Technology Data Exchange (ETDEWEB)

Ibrahim, Amr; Bari, Saiful [Sustainable Energy Centre, School of Advanced Manufacturing and Mechanical Engineering, Univ. of South Australia, Mawson Lakes SA 5095 (Australia)

2009-12-15

Exhaust gas recirculation (EGR) strategy has been recently employed in natural gas SI engines as an alternative to lean burn technique in order to satisfy the increasingly stringent emission standards. However, the effect of EGR on some of engine performance parameters compared to lean burn is not yet quite certain. In the current study, the effect of both EGR and lean burn on natural gas SI engine performance was compared at similar operating conditions. This was achieved numerically by developing a computer simulation of the four-stroke spark-ignition natural gas engine. A two-zone combustion model was developed to simulate the in-cylinder conditions during combustion. A kinetic model based on the extended Zeldovich mechanism was also developed in order to predict NO emission. The combustion model was validated using experimental data and a good agreement between the results was found. It was demonstrated that adding EGR to the stoichiometric inlet charge at constant inlet pressure of 130 kPa decreased power more rapidly than excess air; however, the power loss was recovered by increasing the inlet pressure from 130 kPa at zero dilution to 150 kPa at 20% EGR dilution. The engine fuel consumption increased by 10% when 20% EGR dilution was added at inlet pressure of 150 kPa compared to using 20% air dilution at 130 kPa. However, it was found that EGR dilution strategy is capable of producing extremely lower NO emission than lean burn technique. NO emission was reduced by about 70% when the inlet charge was diluted at a rate of 20% using EGR instead of excess air. (author)

A comparison between EGR and lean-burn strategies employed in a natural gas SI engine using a two-zone combustion model

International Nuclear Information System (INIS)

Ibrahim, Amr; Bari, Saiful

2009-01-01

Exhaust gas recirculation (EGR) strategy has been recently employed in natural gas SI engines as an alternative to lean burn technique in order to satisfy the increasingly stringent emission standards. However, the effect of EGR on some of engine performance parameters compared to lean burn is not yet quite certain. In the current study, the effect of both EGR and lean burn on natural gas SI engine performance was compared at similar operating conditions. This was achieved numerically by developing a computer simulation of the four-stroke spark-ignition natural gas engine. A two-zone combustion model was developed to simulate the in-cylinder conditions during combustion. A kinetic model based on the extended Zeldovich mechanism was also developed in order to predict NO emission. The combustion model was validated using experimental data and a good agreement between the results was found. It was demonstrated that adding EGR to the stoichiometric inlet charge at constant inlet pressure of 130 kPa decreased power more rapidly than excess air; however, the power loss was recovered by increasing the inlet pressure from 130 kPa at zero dilution to 150 kPa at 20% EGR dilution. The engine fuel consumption increased by 10% when 20% EGR dilution was added at inlet pressure of 150 kPa compared to using 20% air dilution at 130 kPa. However, it was found that EGR dilution strategy is capable of producing extremely lower NO emission than lean burn technique. NO emission was reduced by about 70% when the inlet charge was diluted at a rate of 20% using EGR instead of excess air.

Expression of immediate-early genes in the inferior colliculus and auditory cortex in salicylate-induced tinnitus in rat

Directory of Open Access Journals (Sweden)

S.S. Hu

2014-03-01

Full Text Available Tinnitus could be associated with neuronal hyperactivity in the auditory center. As a neuronal activity marker, immediate-early gene (IEG expression is considered part of a general neuronal response to natural stimuli. Some IEGs, especially the activity-dependent cytoskeletal protein (Arc and the early growth response gene-1 (Egr-1, appear to be highly correlated with sensory-evoked neuronal activity. We hypothesize, therefore, an increase of Arc and Egr-1 will be observed in a tinnitus model. In our study, we used the gap prepulse inhibition of acoustic startle (GPIAS paradigm to confirm that salicylate induces tinnitus-like behavior in rats. However, expression of the Arc gene and Egr-1 gene were decreased in the inferior colliculus (IC and auditory cortex (AC, in contradiction of our hypothesis. Expression of N-methyl d-aspartate receptor subunit 2B (NR2B was increased and all of these changes returned to normal 14 days after treatment with salicylate ceased. These data revealed long-time administration of salicylate induced tinnitus markedly but reversibly and caused neural plasticity changes in the IC and the AC. Decreased expression of Arc and Egr-1 might be involved with instability of synaptic plasticity in tinnitus.

Port and EGR Mass Flow Sensors

DEFF Research Database (Denmark)

Hendricks, Elbert

1998-01-01

The note documents briefly work done on what is thought to be a new method of measurement of the pulsating flow in the intake port ot and SI engine and in the EGR returen line. The work reviewed has been carried out in close cooperation with Civ. Ing. Michael Føns, Civ. Ing. Christian Jepsen, the......, the author (IAU) and Spencer C. Sorenson (ET). The theory which decribes in detail the overall dynamic chracteristics of the sensor was developed at IAU and ET, DTU....

Follow-up of prolactin levels in patients with breast cancer metastases treated by cryohypophysectomy

International Nuclear Information System (INIS)

Rozsival, V.; Petr, R.; Kubicek, J.; Hajek, P.; Fingerova, H.; Talas, M.; Janouskova, M.

1981-01-01

In the years 1977 to 1979, prolactin levels were examined in the blood of 39 patients with breast cancer metastases in the skeleton. In 27 patients undergoing surgery, prolactin values were obtained prior to the operation and on the 7th day after stereotactic cryohypophysectomy; in 19 patients the values were obtained also at later intervals. Prolactin was examined using RIA. Prior to surgery, the prolactin levels ranged between 4.3 and above 100 μg/l, with an average of 24.69. Seven days after cryohypophysectomy, the average was 14.01 μg/l, i.e., a remarkable decrease was observed showing considerable significance in the pair test. Prolactin examination in patients with breast cancer metastases showed increased levels above the menopausal standard in almost 80% of the group of patients prior to hypophysectomy. After surgery, a prolactin level decrease was observed in 60% of patients, which confirmed that the intervention in the hypophysis was effective. (author)

SERUM PROLACTIN LEVEL IN ACNE PATIENTS VERSUS CONTROL GROUP: STUDY ON 14 TO 35 YEARS OLD WOMEN

Directory of Open Access Journals (Sweden)

G FAGHIHI

2002-03-01

Full Text Available Introduction. Androgens have a main role in acne pathogenesis. The interaction between prolactin and androgens generate the hypothesis of prolactin role in acne pathogenesis. Methods. In a case - control study, 71 women with modearte to severe acne were compaired with 71 healthy women about their serum prolactin levels. Results. Mean of serum prolactin level was 533 632 miu/lit in cases. Mean of serum prolactin level was 365 363 in control group (P > 0.05. There was a significant correlation between serum prolactin level and severity of acne. Discussion. Despite the non significant difference between serum prolactin level in acne patients and healthy women, thare was a significant relationship between serum prolactin level and severity of acne. It may be due to our small sample size. However, the more powerful studies is needed.

Real-imaging cDNA-AFLP transcript profiling of pancreatic cancer patients: Egr-1 as a potential key regulator of muscle cachexia

Energy Technology Data Exchange (ETDEWEB)

Skorokhod, Alexander [Division of Preventive Oncology, National Center for Tumor Diseases (NCT) Heidelberg, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120, Heidelberg (Germany); Institute of Molecular Biology and Genetics, Ukrainian Academy of Sciences, Zabolotnogo str. 150, 03143, Kiev (Ukraine); Bachmann, Jeannine [Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, Munich (Germany); Giese, Nathalia A [Department of General Surgery, University of Heidelberg, ImNeuenheimer Feld, 110 69120, Heidelberg (Germany); Martignoni, Marc E [Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, Munich (Germany); Krakowski-Roosen, Holger [Division of Preventive Oncology, National Center for Tumor Diseases (NCT) Heidelberg, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120, Heidelberg (Germany)

2012-06-21

Cancer cachexia is a progressive wasting syndrome and the most prevalent characteristic of cancer in patients with advanced pancreatic adenocarcinoma. We hypothesize that genes expressed in wasted skeletal muscle of pancreatic cancer patients may determine the initiation and severity of cachexia syndrome. We studied gene expression in skeletal muscle biopsies from pancreatic cancer patients with and without cachexia utilizing Real-Imaging cDNA-AFLP-based transcript profiling for genome-wide expression analysis. Our approach yielded 183 cachexia-associated genes. Ontology analysis revealed characteristic changes for a number of genes involved in muscle contraction, actin cytoskeleton rearrangement, protein degradation, tissue hypoxia, immediate early response and acute-phase response. We demonstrate that Real-Imaging cDNA-AFLP analysis is a robust method for high-throughput gene expression studies of cancer cachexia syndrome in patients with pancreatic cancer. According to quantitative RT-PCR validation, the expression levels of genes encoding the acute-phase proteins α-antitrypsin and fibrinogen α and the immediate early response genes Egr-1 and IER-5 were significantly elevated in the skeletal muscle of wasted patients. By immunohistochemical and Western immunoblotting analysis it was shown, that Egr-1 expression is significantly increased in patients with cachexia and cancer. This provides new evidence that chronic activation of systemic inflammatory response might be a common and unifying factor of muscle cachexia.

Real-imaging cDNA-AFLP transcript profiling of pancreatic cancer patients: Egr-1 as a potential key regulator of muscle cachexia

International Nuclear Information System (INIS)

Skorokhod, Alexander; Bachmann, Jeannine; Giese, Nathalia A; Martignoni, Marc E; Krakowski-Roosen, Holger

2012-01-01

Cancer cachexia is a progressive wasting syndrome and the most prevalent characteristic of cancer in patients with advanced pancreatic adenocarcinoma. We hypothesize that genes expressed in wasted skeletal muscle of pancreatic cancer patients may determine the initiation and severity of cachexia syndrome. We studied gene expression in skeletal muscle biopsies from pancreatic cancer patients with and without cachexia utilizing Real-Imaging cDNA-AFLP-based transcript profiling for genome-wide expression analysis. Our approach yielded 183 cachexia-associated genes. Ontology analysis revealed characteristic changes for a number of genes involved in muscle contraction, actin cytoskeleton rearrangement, protein degradation, tissue hypoxia, immediate early response and acute-phase response. We demonstrate that Real-Imaging cDNA-AFLP analysis is a robust method for high-throughput gene expression studies of cancer cachexia syndrome in patients with pancreatic cancer. According to quantitative RT-PCR validation, the expression levels of genes encoding the acute-phase proteins α-antitrypsin and fibrinogen α and the immediate early response genes Egr-1 and IER-5 were significantly elevated in the skeletal muscle of wasted patients. By immunohistochemical and Western immunoblotting analysis it was shown, that Egr-1 expression is significantly increased in patients with cachexia and cancer. This provides new evidence that chronic activation of systemic inflammatory response might be a common and unifying factor of muscle cachexia

Increased prolactin levels are associated with impaired processing speed in subjects with early psychosis.

Directory of Open Access Journals (Sweden)

Itziar Montalvo

Full Text Available Hyperprolactinaemia, a common side effect of some antipsychotic drugs, is also present in drug-naïve psychotic patients and subjects at risk for psychosis. Recent studies in non-psychiatric populations suggest that increased prolactin may have negative effects on cognition. The aim of our study was to explore whether high plasma prolactin levels are associated with poorer cognitive functioning in subjects with early psychoses. We studied 107 participants: 29 healthy subjects and 78 subjects with an early psychosis (55 psychotic disorders with <3 years of illness, 23 high-risk subjects. Cognitive assessment was performed with the MATRICS Cognitive Consensus Cognitive Battery, and prolactin levels were determined as well as total cortisol levels in plasma. Psychopathological status was assessed and the use of psychopharmacological treatments (antipsychotics, antidepressants, benzodiazepines recorded. Prolactin levels were negatively associated with cognitive performance in processing speed, in patients with a psychotic disorder and high-risk subjects. In the latter group, increased prolactin levels were also associated with impaired reasoning and problem solving and poorer general cognition. In a multiple linear regression analysis conducted in both high-risk and psychotic patients, controlling for potential confounders, prolactin and benzodiazepines were independently related to poorer cognitive performance in the speed of processing domain. A mediation analysis showed that both prolactin and benzodiazepine treatment act as mediators of the relationship between risperidone/paliperidone treatment and speed of processing. These results suggest that increased prolactin levels are associated with impaired processing speed in early psychosis. If these results are confirmed in future studies, strategies targeting reduction of prolactin levels may improve cognition in this population.

Development Of Radioimmunoassay For Prolactin HORMONE Using Solid Phase Magnetic Particles

International Nuclear Information System (INIS)

SHAFIK, H.M.; MEHANY, N.L.

2009-01-01

The preparation and development of primary reagents of prolactin (PRL) radioimmunoassay (RIA) technique using solid phase magnetic particles with low cost is considered to be the main objective of the present study. The production of polyclonal antibodies was undertaken by immunizing four female New-Zealand rabbits through primary injection and four booster doses subcutaneously. The preparation of 125 I-prolactin radiotracer was carried out using chloramine-T. The preparation of standard prolactin was undertaken by preparing stock standard solution of prolactin and diluted with assay buffer. Activation and coupling of low magnetizable particles with the purified anti-PRL was carried out. Optimization and validation of the assay were carried out. The results obtained provide a highly sensitive, specific and accurate RIA system of PRL. In conclusion, this assay could be used in diagnosis of galactorrhea, prolactinoma, visual impairment and diagnosis of infertility in males and females.

Increased prolactin levels are associated with impaired processing speed in subjects with early psychosis.

Science.gov (United States)

Montalvo, Itziar; Gutiérrez-Zotes, Alfonso; Creus, Marta; Monseny, Rosa; Ortega, Laura; Franch, Joan; Lawrie, Stephen M; Reynolds, Rebecca M; Vilella, Elisabet; Labad, Javier

2014-01-01

Hyperprolactinaemia, a common side effect of some antipsychotic drugs, is also present in drug-naïve psychotic patients and subjects at risk for psychosis. Recent studies in non-psychiatric populations suggest that increased prolactin may have negative effects on cognition. The aim of our study was to explore whether high plasma prolactin levels are associated with poorer cognitive functioning in subjects with early psychoses. We studied 107 participants: 29 healthy subjects and 78 subjects with an early psychosis (55 psychotic disorders with levels were determined as well as total cortisol levels in plasma. Psychopathological status was assessed and the use of psychopharmacological treatments (antipsychotics, antidepressants, benzodiazepines) recorded. Prolactin levels were negatively associated with cognitive performance in processing speed, in patients with a psychotic disorder and high-risk subjects. In the latter group, increased prolactin levels were also associated with impaired reasoning and problem solving and poorer general cognition. In a multiple linear regression analysis conducted in both high-risk and psychotic patients, controlling for potential confounders, prolactin and benzodiazepines were independently related to poorer cognitive performance in the speed of processing domain. A mediation analysis showed that both prolactin and benzodiazepine treatment act as mediators of the relationship between risperidone/paliperidone treatment and speed of processing. These results suggest that increased prolactin levels are associated with impaired processing speed in early psychosis. If these results are confirmed in future studies, strategies targeting reduction of prolactin levels may improve cognition in this population.

Fundamental studies, reference values and relationship to menstrual cycle on Prolactin RIA BEAD II

International Nuclear Information System (INIS)

Kobayashi, Midori; Sakai, Rinko; Satoh, Shigekiyo; Maruyama, Kiyoji; Kanai, Masamitsu

1989-01-01

We have tried fundamental studies, reference values and relationship to menstrual cycle on Prolactin RIA BEAD II kit which has a method of IRMA using monocronal antibody. On clinical studies, we investigated change of serum prolactin level during the menstrual cycle and relationship to other hormones (LH, FSH, estradiol, progesterone). It was the result that prolactin level of follicular phase was lower than that of preavulatory phase and luteal phase. We conclude that change of prolactin level during the menstrual cycle is related with change of estradiol level. (author)

Fundamental studies, reference values and relationship to menstrual cycle on Prolactin RIA BEAD II

Energy Technology Data Exchange (ETDEWEB)

Kobayashi, Midori; Sakai, Rinko; Satoh, Shigekiyo; Maruyama, Kiyoji; Kanai, Masamitsu (Shinshu Univ., Matsumoto, Nagano (Japan). Faculty of Medicine)

1989-06-01

We have tried fundamental studies, reference values and relationship to menstrual cycle on Prolactin RIA BEAD II kit which has a method of IRMA using monocronal antibody. On clinical studies, we investigated change of serum prolactin level during the menstrual cycle and relationship to other hormones (LH, FSH, estradiol, progesterone). It was the result that prolactin level of follicular phase was lower than that of preavulatory phase and luteal phase. We conclude that change of prolactin level during the menstrual cycle is related with change of estradiol level. (author).

The IAV active High-EGR concept; Das aktive Hoch-AGR-Konzept der IAV

Energy Technology Data Exchange (ETDEWEB)

Rohrssen, Karsten; Hoeffeler, Gerd [IAV GmbH, Gifhorn (Germany). Geschaeftsbereich Powertrain Mechatronik

2011-01-15

Exhaust gas recirculation (EGR) is a proven method of emissions reduction in diesel engines. The higher the exhaust gas rates in the combustion air, the more nitrogen oxide emissions are reduced. To meet always higher demands, IAV has developed the active High-EGR concept where a twin screw compressor with a newly developed rotary slide control has been placed between the exhaust-gas turbocharger and the motor. Driven by a pulley drive planetary gear with power split, the charger is able to actively compress fresh air and exhaust gas and to to mix the two elements to the desired ratio. (orig.)

Controlling the heat release in HCCI combustion of DME with methanol and EGR

DEFF Research Database (Denmark)

Pedersen, Troels Dyhr; Schramm, Jesper; Yanai, Tadanori

2010-01-01

quantity required was determined. The added methanol increased the BMEP by increasing the total heat release and retarding the combustion to after TDC. Engine knock was reduced with increasing quantities of methanol. The highest BMEP was achieved when the equivalence ratio of methanol was around 0.......12 at 1000 RPM, and around 0.76 at 1800 RPM. EGR was also used to retarding the timing. With a moderate amount of EGR the effect on the combustion was not notable, but as the equivalence ratio approached unity the combustion was increasingly delayed and the rate of reaction reduced. Engine knock seized...

The Effect of Exhaust Gas Recirculation (EGR on the Emission of a Single Cylinder Spark Ignition Engine

Directory of Open Access Journals (Sweden)

Limyaa Mahdi Asaad

2016-07-01

Full Text Available A single cylinder variable compression ratio spark ignition engine type PRODIT was used in this study. The  experiments  were  conducted  with  gasoline  fuel  (80  octane  No.at  equivalence  ratio  (Ø  =1.  This study examined the effects of exhaust gas recirculation on emission. It was conducted at engine speeds (1500, 1900, 2300 and 2700 r.p.m..The  exhaust  gases  were  added  in  volumetric  ratios  of  10%,  20%  and  30%  of  the  entering  air/fuel charge. The results showed that the EGR addition decreases the CO2 concentrations, in the same time CO and HC concentrations increase remarkably.  NOx concentration decreased highly with the increase of EGR percentage at variable engine speeds and constant torque. Also, it decreased when the engine run  at  constant  speed  and  variable  engine  torque.  The  exhaust  gas  temperature  decreased  with increasing EGR ratio.

Serum prolactin profiles of normal human conception cycles

Energy Technology Data Exchange (ETDEWEB)

Adejuwon, C A [Ibadan Univ. (Nigeria). Coll. of Medicine; Faundes, Anibal [Universidade Estadual de Campinas (Brazil). Faculdade de Medicina; Segal, S J [Rockefeller Foundation, New York (USA); Alvarez-Sanchez, Francisco [Hospital Moscoso Puello, Santo Domingo (Dominican Republic). Dept. of Obstet. and Gynaecol.

1984-06-01

Commencing on day 10 of the menstrual cycle through onset of subsequent menses, or confirmation of pregnancy, daily sera collected from 15 women planning pregnancy were analyzed by radioimmunoassays (RIA) for prolactin (hPRL), estradiol-17..beta.. and luteinizing hormone (hLH). Two of the observed subjects became pregnant in the single cycles studied. The profiles of these hormones during the early gestation following spontaneous ovulation were established. No distinct midcycle peaks of hPEL were observed in either subject. Enormous spikes were observed in daily prolactin values, with wide variations between subjects.

Prolactin, thyrotropin, and growth hormone release during stress associated with parachute jumping.

Science.gov (United States)

Noel, G L; Dimond, R C; Earll, J M; Frantz, A G

1976-05-01

Prolactin, growth hormone, and thyrotropin (TSH) release during the stress of parachute jumping has been evaluated in 14 male subjects. Subjects were studied at several times before and immediately after their first military parachute jump. All three hormones had risen significantly 1 to 14 min after the jump, compared to mean levels measured immediately beforehand. Earlier studies of physical exercise by ourselves and others would suggest that emotional stress played a role in producing changes of this magnitude. We conclude that prolactin, TSH, and growth hormone are released in physiologically significant amounts in association with the stress of parachute jumping.

Effect of gonadotrophin inhibiting material isolated from human urine on action of prolactin at rat Leydig cell

Energy Technology Data Exchange (ETDEWEB)

Bagli, N P; Rajendran, K G; Shah, P N [Cancer Research Inst., Bombay (India). Div. of Endocrinology

1980-05-01

To study the effect of gonadotropin inhibiting material (GIM) on the binding of prolactin to Leydig cell receptors isolated Leydig cells were incubated with sup(125)I-prolactin. Presence of GIM in the incubation mixture did not inhibit the binding of sup(125)I-prolactin to Leydig cells whereas unlabelled prolactin significantly reduced the binding. In another experiment, testicular cells were incubated with FITC-tagged GIM. Binding of GIM to Leydig cells was seen by the presence of fluorescence on these cells. This binding could be inhibited by untagged GIM but not by prolactin. The results suggest the presence of separate receptors for GIM and prolactin on the Leydig cells and indicate that termination of pregnancy by GIM is not due to any interference with prolactin binding to its receptors.

Effects of bovine prolactin gene polymorphism within exon 4 on milk ...

African Journals Online (AJOL)

In this study, polymorphism of prolactin gene was analyzed as a candidate gene responsible for variation and genetic trends in milk yield and composition traits. Genomic DNAs were extracted from 268 semen samples belonged to Iranian Holstein bulls. Genotyping for the prolactin gene using PCRRFLP technique and RsaI ...

Study of gas (CNG) SI engine with pre-chamber. Improvement of the indicated thermal efficiency on lean mixture with EGR and supercharging; Fukushitsushiki hibana tenka asshuku tennen gas (CNG) engine ni kansuru kenkyu. Kakyu to EGR ni yoru kihakuiki no netsukoritsu kaizen

Energy Technology Data Exchange (ETDEWEB)

Yonetani, H.; Fukutani, I. [Polytechnic University, Kanagawa (Japan)

1998-10-15

As lean burn of compressed natural gas (CNG) is applied to conventional gasoline engines, a combustion period largely increases, resulting in large combustion fluctuation and low thermal efficiency. Heterogeneous spacial air/fuel ratios also have an effect on combustion in lean burn area. By preparing a pre-chamber for a combustion chamber of high- compression ratio CNG pre-mixing SI engines to utilize premixture turbulence, rapid flame propagation is obtained in lean burn area, resulting high combustion performance. Furthermore, study was made on improvement of combustion performance in lean burn area under various compression ratios, intake pressures, pre-chamber shapes and EGR ratios. As a result, lean burn operation at high intake pressure by supercharging showed possible improvement of a thermal efficiency and expansion of inflammable limits. Higher thermal efficiency in lean burn area was also obtained by using higher compression ratios considering heat loss. Although EGR was effective in controlling NOx formed in lean burn area, strict control of both air excess rate and EGR rate was required to prevent lower thermal efficiency. 2 refs., 8 figs., 1 tab.

Excitatory and inhibitory effects of prolactin release activated by nerve stimulation in rat anterior pituitary

Directory of Open Access Journals (Sweden)

Gao Li-Zhi

2009-12-01

Full Text Available Abstract Background A series of studies showed the presence of substantial amount of nerve fibers and their close relationship with the anterior pituitary gland cells. Our previous studies have suggested that aside from the classical theory of humoral regulation, the rat anterior pituitary has direct neural regulation on adrenocorticotropic hormone release. In rat anterior pituitary, typical synapses are found on every type of the hormone-secreting cells, many on lactotrophs. The present study was aimed at investigating the physiological significance of this synaptic relationship on prolactin release. Methods The anterior pituitary of rat was sliced and stimulated with electrical field in a self-designed perfusion chamber. The perfusate was continuously collected in aliquots and measured by radioimmunoassay for prolactin levels. After statistic analysis, differences of prolactin concentrations within and between groups were outlined. Results The results showed that stimulation at frequency of 2 Hz caused a quick enhancement of prolactin release, when stimulated at 10 Hz, prolactin release was found to be inhibited which came slower and lasted longer. The effect of nerve stimulation on prolactin release is diphasic and frequency dependent. Conclusions The present in vitro study offers the first physiological evidence that stimulation of nerve fibers can affect prolactin release in rat anterior pituitary. Low frequency stimulation enhances prolactin release and high frequency mainly inhibits it.

Local production of donkey anti-rabbit's sera for human prolactin radioimmunoassay

International Nuclear Information System (INIS)

Hassan, Ammar Mohamed Elamin

2001-11-01

Pure Rabbit's IgG was used in this study to raise donkey anti rabbit's sera to be used as separating agent in radioimmunoassay. Two healthy donkeys have been immunized. The anti rabbit's sera have been titrated as (i) crude, (ii) purified and dialysed coupled to magnetic particles. Then this antibody was used as separating agent in a radioimmunoassay for measurement of human prolactin (PRL). Coupled Sudanese donkey and rabbit's sera (Sud-DARS) was used as 1/8 titre using chelsea RIA kit for human prolactin while 1/200 of liquid Sud-DARS was found to be the best titre using the Chinese kit. The best condition for estimation of the prolactin were optimized by determining the suitable incubation time and temperature. The assay can be done at room temperature but it should be incubated for 6 hours as recommended by the Chinese kit. Validity tests were done. The regression coefficients were 0.994 and 0.999 for linearity and recovery tests respectively. Measurement of human PRL wa found to be reproducible using Sud-DARS as separating agent since the coefficient of variation (C.V. %) was found to be less than 15% for both within batch and between assays. Comparing Sud D ARS to the Chinese kit, separating agent as reference agent, regression coefficient was found to be 0.977 which indicate that Sud-DARS can be used as separating agent. Prolactin in Sudanese subject was determined using the Chinese kit the Sud-DARS as separating agent. The ranges were 74-398 mIU/L in males and 102-414 mI/L in the preovulatory phase for the females while in the post ovulatory phase it was 114-442 mIU/L. Ovulation was confirmed by measurement of progesterone level 7 days before the next suspected mensuration. (Author)

Immunological properties of prolactin and studies on a gonadotropin binding inhibitor

International Nuclear Information System (INIS)

Chang, Y.S.

1985-01-01

The physiological role of prolactin in horses has not yet been well defined. With the availability of highly purified ePRL for inducing antibody formation in rabbits and for radiolabeling with Na 125 I, a very sensitive (0.4-0.6 ng/ml) and highly specific homologous RIA for ePRL was developed. A heterologous RIA using 125 I-labeled ovine PRL and anti-ePRL antiserum was also developed and compared to the homologous RIA for ePRL. Of the two systems, it is concluded that this homologous RIA system is more suitable and more reliable for measuring prolactin concentration in horse serum samples. Until now, biochemical information on PRL has not been available for reptilian species. Sea turtle (Chelonia mydas) prolactin was purified from pituitary extracts by selective precipitation, DEAE-cellulose chromatography and gel filtration. Similar to other species of PRL, sea turtle PRL is a 22,000-24,000 daltons protein and contains a high content of glutamic acid, aspartic acid, serine and leucine, the N-terminal amino acid residue. Gonadotropin (FSH) binding inhibitor was partially purified from sheep testes by ammonium sulfate fractionation and ion exchange chromatography. The FSH-BI (molecular weight: 50,000 daltons, estimated by gel filtration) contains a protein moiety necessary for binding inhibitory activity. The inhibition of the binding of 125 I-labeled ovine FSH to its receptor by the FSH-BI is not competitive. Both in vivo and in vitro biological studies of FSH-BI preparations in rats indicated various effects on FSH and LH activities at the gonadal level. These findings suggest a physiological role for FSH-BI in the regulation of reproduction

Prolactin effect on the insulin content of albino rats in different physiological states

International Nuclear Information System (INIS)

Megahed, Y.M.; Abdel-Wahab, M.F.; El-Mougi, S.M.; El-Sayed, F.B.; Kuwait Univ.)

1980-01-01

The metabolic action of prolactin on insulin levels in plasma and pancreas has been studied. Prolactin was injected in a single dose or single daily doses on 4 successive days into albino rats in six different physiological states. Insulin was determined by radioimmunoassay using 125 I insulin. From the results it is concluded that prolactin injected i.p. influences the output of insulin and stimulates the pancreas to secrete insulin into the plasma. (author)

Effect of exogenous prolactin on ultrastructure of pinealocyte in female pigs during puberty

International Nuclear Information System (INIS)

Przybylska, B.; Dusza, L.; Lewczuk, B.; Ciesielska-Myszka, L.

1994-01-01

Influence of the administration of prolactin to female swine during puberty on the ultrastructure of pinealocytes has been examined by means of morphometric analysis. Prolactin administration for 15 consecutive days resulted in a decrease in the cytoplasmic dense bodies type MBB-2, lysosomes and multivesicular bodies. Some differences in structure of pinealocytes were also observed. Prolactin appeared to stimulate the process of transformation of cytoplasmic dense bodies. (author). 28 refs, 5 figs

Effect of exogenous prolactin on ultrastructure of pinealocyte in female pigs during puberty

Energy Technology Data Exchange (ETDEWEB)

Przybylska, B.; Dusza, L.; Lewczuk, B.; Ciesielska-Myszka, L. [Akademia Rolniczo-Technicza, Olsztyn (Poland)

1994-12-31

Influence of the administration of prolactin to female swine during puberty on the ultrastructure of pinealocytes has been examined by means of morphometric analysis. Prolactin administration for 15 consecutive days resulted in a decrease in the cytoplasmic dense bodies type MBB-2, lysosomes and multivesicular bodies. Some differences in structure of pinealocytes were also observed. Prolactin appeared to stimulate the process of transformation of cytoplasmic dense bodies. (author). 28 refs, 5 figs.

Prolactin and Male Fertility: The Long and Short Feedback Regulation

Directory of Open Access Journals (Sweden)

M. K. Gill-Sharma

2009-01-01

Full Text Available In the last 20 years, a pituitary-hypothalamus tissue culture system with intact neural and portal connections has been developed in our lab and used to understand the feedback mechanisms that regulate the secretions of adenohypophyseal hormones and fertility of male rats. In the last decade, several in vivo rat models have also been developed in our lab with a view to substantiate the in vitro findings, in order to delineate the role of pituitary hormones in the regulation of fertility of male rats. These studies have relied on both surgical and pharmacological interventions to modulate the secretions of gonadotropins and testosterone. The interrelationship between the circadian release of reproductive hormones has also been ascertained in normal men. Our studies suggest that testosterone regulates the secretion of prolactin through a long feedback mechanism, which appears to have been conserved from rats to humans. These studies have filled in a major lacuna pertaining to the role of prolactin in male reproductive physiology by demonstrating the interdependence between testosterone and prolactin. Systemic levels of prolactin play a deterministic role in the mechanism of chromatin condensation during spermiogenesis.

high doses of prolactin inhibit testosterone secretion in rat leydig cells

African Journals Online (AJOL)

Femi Olaleye

1 The effect of prolactin on dispersed rat Leydig cells was investigated. Leydig cells from adult rat testes of proven fertility were isolated via collagenase digestion and dispersion. About 100,000 Leydig .... Hormones, Drugs and Reagents.

Prolactin modulates luteal activity in the short-nosed fruit bat, Cynopterus sphinx during delayed embryonic development.

Science.gov (United States)

Anuradha; Krishna, Amitabh

2017-07-01

The aim of this study was to evaluate the role of prolactin as a modulator of luteal steroidogenesis during the period of delayed embryonic development in Cynopterus sphinx. A marked decline in circulating prolactin levels was noted during the months of November through December coinciding with the period of decreased serum progesterone and delayed embryonic development. The seasonal changes in serum prolactin levels correlated positively with circulating progesterone (P) level, but inversely with circulating melatonin level during first pregnancy showing delayed development in Cynopterus sphinx. The results also showed decreased expression of prolactin receptor-short form (PRL-RS) both in the corpus luteum and in the utero-embryonic unit during the period of delayed embryonic development. Bats treated in vivo with prolactin during the period of delayed development showed significant increase in serum progesterone and estradiol levels together with significant increase in the expression of PRL-RS, luteinizing hormone receptor (LH-R), steroidogenic acute receptor protein (STAR) and 3β-hydroxysteroid dehydrogenase (3β-HSD) in the ovary. Prolactin stimulated ovarian angiogenesis (vascular endothelial growth factor) and cell survival (B-cell lymphoma 2) in vivo. Significant increases in ovarian progesterone production and the expression of prolactin-receptor, LH-R, STAR and 3β-HSD proteins were noted following the exposure of LH or prolactin in vitro during the delayed period. In conclusion, short-day associated increased melatonin level may be responsible for decreased prolactin release during November-December. The decline in prolactin level might play a role in suppressing P and estradiol-17β (E2) estradiol levels thereby causing delayed embryonic development in C. sphinx. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of EGR on the exhaust gas temperature and exhaust opacity ...

Indian Academy of Sciences (India)

R. Narasimhan (Krishtel eMaging) 1461 1996 Oct 15 13:05:22

injection, turbo-charging, air-to-air inter-cooling, combustion optimization with and .... (iii) Partly cooled EGR: To avoid water condensation, the temperature of the ... A two-cylinder constant speed diesel engine generator set is used in present ...

Effects of bovine prolactin gene polymorphism within exon 4 on milk ...

African Journals Online (AJOL)

STORAGESEVER

2009-10-05

Oct 5, 2009 ... In this study, polymorphism of prolactin gene was analyzed as a candidate gene responsible for ... studied. Based on important role of prolactin gene in milk related traits and their genetic trends in dairy cattle, the aims of this study were, to screen ..... isolation and selection towards high fat and protein per-.

Role of basal and provocative serum prolactin in differentiating idiopathic hypogonadotropic hypogonadism and constitutional delayed puberty--a diagnostic dilemma.

Science.gov (United States)

Ali, Liaqat; Adeel, Afrose

2012-01-01

The prevalence of Idiopathic Hypogonadotropic Hypogonadism (IHH) is approximately 1 in 10,000 men. Objectives of this study were to evaluate the role of basal and stimulated serum prolactin in differentiating Constitutional Delayed Puberty (CDP) from IHH. This cross-sectional study was carried out at the Department of Diabetes and Endocrinology, Military Hospital, Rawalpindi. A total of 20 male patients presenting with provisional diagnosis of IHH/CDP were enrolled in the study. Patients with known diseases were excluded from the study. Baseline FSH, LH, testosterone, and prolactin were estimated and the patients were subjected to provocative prolactin stimulation by Thyrotropin releasing hormone stimulation (TRH) test and chlorpromazine challenge. At each 6 monthly follow-up visit for 4 years, the patients were evaluated for adrenarche, pubarche and other secondary sexual characters. Tanner scale was taken as standards for comparing stage of puberty at a particular age. No treatment was given to both groups for 2 years. At the end of 2 years IHH patients with failed puberty or progression of puberty and CDP who lagged behind by more than 2 years by Tanner scale or 4 years per bone age with compelling psychosocial or psychosexual reasons at school or at home were given short courses of 50 mg injection testosterone in an attempt to expedite the onset or progression of puberty. Patients from either group with failed puberty after low dose testosterone were managed with high dose testosterone therapy to induce secondary sexual characters. Twenty patients enrolled in the study were provisionally divided into 2 groups called IHH (n = 9), and CDP (n = 11) based on high basal and provocative serum prolactin levels in CDP group. Two patients from CDP group were lost in the follow-up leaving 9 patients in each group. A total of 10 (56%) patients, 3 (17%) from IHH group and 7 (39%) from CDP group achieved grade 4 puberty without any treatment. Remaining 8 (44%) patients, 6

Gross cystic disease fluid protein-15/prolactin-inducible protein as a biomarker for keratoconus disease.

Directory of Open Access Journals (Sweden)

Shrestha Priyadarsini

Full Text Available Keratoconus (KC is a bilateral degenerative disease of the cornea characterized by corneal bulging, stromal thinning, and scarring. The etiology of the disease is unknown. In this study, we identified a new biomarker for KC that is present in vivo and in vitro. In vivo, tear samples were collected from age-matched controls with no eye disease (n = 36 and KC diagnosed subjects (n = 17. Samples were processed for proteomics using LC-MS/MS. In vitro, cells were isolated from controls (Human Corneal Fibroblasts-HCF and KC subjects (Human Keratoconus Cells-HKC and stimulated with a Vitamin C (VitC derivative for 4 weeks, and with one of the three transforming growth factor-beta (TGF-β isoforms. Samples were analyzed using real-time PCR and Western Blots. By using proteomics analysis, the Gross cystic disease fluid protein-15 (GCDFP-15 or prolactin-inducible protein (PIP was found to be the best independent biomarker able to discriminate between KC and controls. The intensity of GCDFP-15/PIP was significantly higher in healthy subjects compared to KC-diagnosed. Similar findings were seen in vitro, using a 3D culture model. All three TGF-β isoforms significantly down-regulated the expression of GCDFP-15/PIP. Zinc-alpha-2-glycoprotein (AZGP1, a protein that binds to PIP, was identified by proteomics and cell culture to be highly regulated. In this study by different complementary techniques we confirmed the potential role of GCDFP-15/PIP as a novel biomarker for KC disease. It is likely that exploring the GCDFP-15/PIP-AZGP1 interactions will help better understand the mechanism of KC disease.

Rotating night shift work, sleep quality, selected lifestyle factors and prolactin concentration in nurses and midwives.

Science.gov (United States)

Bukowska, Agnieszka; Sobala, Wojciech; Peplonska, Beata

2015-04-01

The pattern of secretion of many hormones, including prolactin, is dependent on the circadian rhythm. Night shift work involves exposure to artificial light at night and sleep deficiency, which in turn can affect prolactin synthesis. The aim of this study was to evaluate a possible association between night shift work characteristics, sleep quality, lifestyle factors and prolactin concentration, using data from a cross-sectional study of nurses and midwives. A cross-sectional study was conducted among 327 nurses and midwives currently working on rotating night shifts, and 330 nurses and midwives working during the day (aged 40-60 years) (388 premenopausal and 269 postmenopausal). Information about night shift work characteristics, lifestyle, reproductive factors, sleep pattern and other covariates was collected through a face-to-face interview, and from a one-week work and sleep diary completed by the subjects. Weight and height were measured. Prolactin concentration was measured in the morning blood sample using the electrochemiluminesence immunoassay method. Associations were analyzed using linear regression models adjusted for important confounders. Analyses were carried out separately in pre- and postmenopausal women. None of the night shift work or sleep characteristics was significantly associated with prolactin concentration. Prolactin concentration was significantly (p night shift work is not associated with prolactin concentration. Smoking, parity, time of blood collection and age among postmenopausal women were significant determinants of prolactin.

Studi Experimental Penggunaan Venturi Scrubber Dan Cyclonic Separator Untuk Meningkatkan Kinerja Pada Sistem Exhaust Gas Recirculation (EGR) Dalam Menurunkan NOX Pada Motor Diesel

OpenAIRE

N, Samsu Dlukha; Ariana, I Made; Fathallah, Aguk Z. M

2012-01-01

Salah satu cara yang efektif untuk mengurangi NOX adalah dengan menggunakan metode Exhaust Gas Recirculation (EGR). Dengan metode EGR, oksigen yang masuk ke ruang bakar akan berkurang sehingga NOX dapat diturunkan dengan signifikan, akan tetapi power dari mesin tersebut juga akan berkurang dan Particulate Matter (PM) akan naik secara signifikan. Dalam penelitian ini dibahas penggunaan EGR yang telah di optimalkan dengan penambahan venturi scrubber dan cyclonic separator, tujuannya mengurangi ...

Efficient EGR technology for future HD diesel engine emission targets

NARCIS (Netherlands)

Baert, R.S.G.; Beckman, D.E.; Veen, A.

1999-01-01

Different systems for achieving short-route cooled EGR on turbocharged and aftercooled heavy-duty diesel engines have been tested on a 12 litre 315 kW engine with 4 valves per cylinder and an electronically controlled unit pump fuel injection system. In all of these systems the exhaust gas was

Comprehensive genome-wide analysis of the Aux/IAA gene family in Eucalyptus: evidence for the role of EgrIAA4 in wood formation.

Science.gov (United States)

Yu, Hong; Soler, Marçal; San Clemente, Hélène; Mila, Isabelle; Paiva, Jorge A P; Myburg, Alexander A; Bouzayen, Mondher; Grima-Pettenati, Jacqueline; Cassan-Wang, Hua

2015-04-01

Auxin plays a pivotal role in various plant growth and development processes, including vascular differentiation. The modulation of auxin responsiveness through the auxin perception and signaling machinery is believed to be a major regulatory mechanism controlling cambium activity and wood formation. To gain more insights into the roles of key Aux/IAA gene regulators of the auxin response in these processes, we identified and characterized members of the Aux/IAA family in the genome of Eucalyptus grandis, a tree of worldwide economic importance. We found that the gene family in Eucalyptus is slightly smaller than that in Populus and Arabidopsis, but all phylogenetic groups are represented. High-throughput expression profiling of different organs and tissues highlighted several Aux/IAA genes expressed in vascular cambium and/or developing xylem, some showing differential expression in response to developmental (juvenile vs. mature) and/or to environmental (tension stress) cues. Based on the expression profiles, we selected a promising candidate gene, EgrIAA4, for functional characterization. We showed that EgrIAA4 protein is localized in the nucleus and functions as an auxin-responsive repressor. Overexpressing a stabilized version of EgrIAA4 in Arabidopsis dramatically impeded plant growth and fertility and induced auxin-insensitive phenotypes such as inhibition of primary root elongation, lateral root emergence and agravitropism. Interestingly, the lignified secondary walls of the interfascicular fibers appeared very late, whereas those of the xylary fibers were virtually undetectable, suggesting that EgrIAA4 may play crucial roles in fiber development and secondary cell wall deposition. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Regulatory role of prolactin in paternal behavior in male parents: A narrative review

Directory of Open Access Journals (Sweden)

F Hashemian

2016-01-01

Full Text Available In all mammalian species, a combination of neuroendocrine and experiential factors contributes to the emergence of remarkable behavioral changes observed in parental behavior. Yet, our understanding of neuroendocrine bases of paternal behavior in humans is still preliminary and more research is needed in this area. In the present review, the authors summarized hormonal bases of paternal behavior in both human and nonhuman mammalian species and focused on studies on the regulatory role of prolactin in occurrence of paternal behavior. All peer-reviewed journal articles published before 2015 for each area discussed (parental brain, hormonal bases of maternal behavior, hormonal bases of paternal behavior and the role of prolactin in regulation of paternal behavior in nonhuman mammalian species, hormonal bases of paternal behavior and the role of prolactin in regulation of paternal behavior in humans were searched by PubMed, Medline, and Scopus for original research and review articles. Publications between 1973 and 2015 were included. Similar to female parents, elevated prolactin levels in new fathers most probably contribute to child-caring behavior and facilitate behavioral and emotional states attributed to child care. Moreover, elevated parental prolactin levels after childbirth decrease the parents′ libidos so that they invest more in parental care than in fertility behavior. According to the available clinical studies, elevation in the amounts of prolactin levels after childbirth in male parents are probably associated with paternal behavior observed in humans.

Impact of novel palmitoylated prolactin-releasing peptide analogs on metabolic changes in mice with diet-induced obesity.

Directory of Open Access Journals (Sweden)

Veronika Pražienková

Full Text Available Analogs of anorexigenic neuropeptides, such as prolactin-releasing peptide (PrRP, have a potential as new anti-obesity drugs. In our previous study, palmitic acid attached to the N-terminus of PrRP enabled its central anorexigenic effects after peripheral administration. In this study, two linkers, γ-glutamic acid at Lys11 and a short, modified polyethylene glycol at the N-terminal Ser and/or Lys11, were applied for the palmitoylation of PrRP31 to improve its bioavailability. These analogs had a high affinity and activation ability to the PrRP receptor GPR10 and the neuropeptide FF2 receptor, as well as short-term anorexigenic effect similar to PrRP palmitoylated at the N-terminus. Two-week treatment with analogs that were palmitoylated through linkers to Lys11 (analogs 1 and 2, but not with analog modified both at the N-terminus and Lys11 (analog 3 decreased body and liver weights, insulin, leptin, triglyceride, cholesterol and free fatty acid plasma levels in a mouse model of diet-induced obesity. Moreover, the expression of uncoupling protein-1 was increased in brown fat suggesting an increase in energy expenditure. In addition, treatment with analogs 1 and 2 but not analog 3 significantly decreased urinary concentrations of 1-methylnicotinamide and its oxidation products N-methyl-2-pyridone-5-carboxamide and N-methyl-4-pyridone-3-carboxamide, as shown by NMR-based metabolomics. This observation confirmed the previously reported increase in nicotinamide derivatives in obesity and type 2 diabetes mellitus and the effectiveness of analogs 1 and 2 in the treatment of these disorders.

Targeting Stromal Androgen Receptor Suppresses Prolactin-Driven Benign Prostatic Hyperplasia (BPH)

Science.gov (United States)

Lai, Kuo-Pao; Huang, Chiung-Kuei; Fang, Lei-Ya; Izumi, Kouji; Lo, Chi-Wen; Wood, Ronald; Kindblom, Jon; Yeh, Shuyuan

2013-01-01

Stromal-epithelial interaction plays a pivotal role to mediate the normal prostate growth, the pathogenesis of benign prostatic hyperplasia (BPH), and prostate cancer development. Until now, the stromal androgen receptor (AR) functions in the BPH development, and the underlying mechanisms remain largely unknown. Here we used a genetic knockout approach to ablate stromal fibromuscular (fibroblasts and smooth muscle cells) AR in a probasin promoter-driven prolactin transgenic mouse model (Pb-PRL tg mice) that could spontaneously develop prostate hyperplasia to partially mimic human BPH development. We found Pb-PRL tg mice lacking stromal fibromuscular AR developed smaller prostates, with more marked changes in the dorsolateral prostate lobes with less proliferation index. Mechanistically, prolactin mediated hyperplastic prostate growth involved epithelial-stromal interaction through epithelial prolactin/prolactin receptor signals to regulate granulocyte macrophage-colony stimulating factor expression to facilitate stromal cell growth via sustaining signal transducer and activator of transcription-3 activity. Importantly, the stromal fibromuscular AR could modulate such epithelial-stromal interacting signals. Targeting stromal fibromuscular AR with the AR degradation enhancer, ASC-J9®, led to the reduction of prostate size, which could be used in future therapy. PMID:23893956

Effects of melatonin and prolactin in reproduction: review of literature

OpenAIRE

Tenorio, Fernanda das Chagas Angelo Mendes; Simões, Manuel de Jesus; Teixeira, Valéria Wanderley; Teixeira, Álvaro Aguiar Coelho

2015-01-01

Summary The pineal gland is responsible for producing a hormone called melatonin (MEL), and is accepted as the gland that regulates reproduction in mammals. Prolactin (PRL) also exhibits reproductive activity in animals in response to photoperiod. It is known that the concentrations of PRL are high in the summer and reduced during winter, the opposite of what is seen with melatonin in these seasons. In placental mammals, both prolactin and melatonin affect implantation, which is considered a ...

Ecological and physiological factors affecting brood patch area and prolactin levels in arctic-nesting geese

Science.gov (United States)

Jonsson, J.E.; Afton, A.D.; Alisauskas, R.T.; Bluhm, C.K.; El Halawani, M.E.

2006-01-01

We investigated effects of ecological and physiological factors on brood patch area and prolactin levels in free-ranging Lesser Snow Geese (Chen caerulescens caerulescens; hereafter “Snow Geese”) and Ross's Geese (C. rossii). On the basis of the body-size hypothesis, we predicted that the relationships between prolactin levels, brood patch area, and body condition would be stronger in Ross's Geese than in the larger Snow Geese. We found that brood patch area was positively related to clutch volume and inversely related to prolactin levels in Ross's Geese, but not in Snow Geese. Nest size, nest habitat, and first egg date did not affect brood patch area in either species. Prolactin levels increased as incubation progressed in female Snow Geese, but this relationship was not significant in Ross's Geese. Prolactin levels and body condition (as indexed by size-adjusted body mass) were inversely related in Ross's Geese, but not in Snow Geese. Our findings are consistent with the prediction that relationships between prolactin levels, brood patch area, and body condition are relatively stronger in Ross's Geese, because they mobilize endogenous reserves at faster rates than Snow Geese.

Human Prolactin Point Mutations and Their Projected Effect on Vasoinhibin Generation and Vasoinhibin-Related Diseases

Directory of Open Access Journals (Sweden)

Jakob Triebel

2017-11-01

Full Text Available BackgroundA dysregulation of the generation of vasoinhibin hormones by proteolytic cleavage of prolactin (PRL has been brought into context with diabetic retinopathy, retinopathy of prematurity, preeclampsia, pregnancy-induced hypertension, and peripartum cardiomyopathy. Factors governing vasoinhibin generation are incompletely characterized, and the composition of vasoinhibin isoforms in human tissues or compartments, such as the circulation, is unknown. The aim of this study was to determine the possible contribution of PRL point mutations to the generation of vasoinhibins as well as to project their role in vasoinhibin-related diseases.MethodsProlactin sequences, point mutations, and substrate specificity information about the PRL cleaving enzymes cathepsin D, matrix metalloproteinases 8 and 13, and bone-morphogenetic protein 1 were retrieved from public databases. The consequences of point mutations in regard to their possible effect on vasoinhibin levels were projected on the basis of a score indicating the suitability of a particular sequence for enzymatic cleavage that result in vasoinhibin generation. The relative abundance and type of vasoinhibin isoforms were estimated by comparing the relative cleavage efficiency of vasoinhibin-generating enzymes.ResultsSix point mutations leading to amino acid substitutions in vasoinhibin-generating cleavage sites were found and projected to either facilitate or inhibit vasoinhibin generation. Four mutations affecting vasoinhibin generation in cancer tissues were found. The most likely composition of the relative abundance of vasoinhibin isoforms is projected to be 15 > 17.2 > 16.8 > 17.7 > 18 kDa vasoinhibin.ConclusionProlactin point mutations are likely to influence vasoinhibin levels by affecting the proteolysis efficiency of vasoinhibin-generating enzymes and should be monitored in patients with vasoinhibin-related diseases. Attempts to characterize vasoinhibin-related diseases

Regulation of breeding behavior: do energy-demanding periods induce a change in prolactin or corticosterone baseline levels in the common tern (Sterna hirundo)?

Science.gov (United States)

Riechert, Juliane; Chastel, Olivier; Becker, Peter H

2014-01-01

Hormones are involved in reproductive decisions, linking environmental cues and body condition and adapting behavior. Mass loss is often accompanied by decreased prolactin and increased corticosterone concentrations, influencing incubation and brooding behavior and ultimately triggering nest desertion. Using blood-sucking bugs (Dipetalogaster maxima), we measured baseline prolactin, corticosterone, and ketone body values in incubating common terns (Sterna hirundo) between 2006 and 2009 during energy-demanding periods: 50 pairs were sampled hungry (after an incubation bout) and again fed (after foraging). In a second approach, we sampled 57 other pairs (experienced and inexperienced birds) three times over their individual breeding period, because reproduction, especially chick rearing, is a very energy-demanding process. In line with the common physiological pattern of fasting, we found significantly lower baseline prolactin values in hungry terns, which were negatively related to mass loss over the incubation bout, whereas corticosterone and ketone body levels were marginally increased. Compared to that in the incubation phase, the prolactin level dropped after hatching of chicks in inexperienced birds, perhaps indicating lower parental expenditure. Corticosterone, on the other hand, increased after hatching in males, probably linked to higher foraging activity, as males mainly deliver food during the first days. These energy-demanding periods clearly influenced hormones and ketone bodies, maybe reinforced by the low energy margin of this small seabird species, but energy reserves were not depleted to a level affecting behavior or reproductive success.

[Effect of estradiol on the prolactin content in the adenohypophysis of sexually mature and immature rats].

Science.gov (United States)

Arse, Kh A

1979-01-01

Gel electrophoresis was used in a comparative study of prolactin content in the hypophysis of rats of different age and sex, and at various stages of the estral cycle. The hormone level in the pubertal rats was twice or thrice greater than in the immature ones; it was by 16% less at the diestrus than at the estrus stage. There was no change in the hypophysis prolactin content in male rats at puberty. Ovariectomy was accompained by a sharp reduction of prolactin in the hypophysis. Replacing estradiol therapy increased the amount of prolactin in the hypophysis, without bringing it, however, to the level characteristic of intact rats. Estrogens are responsible for the maintenance of prolactin level, but apparently other factors influencing its content in the hypophysis also exist.

Change in Prolactin Levels in Pediatric Patients Given Antipsychotics for Schizophrenia and Schizophrenia Spectrum Disorders: A Network Meta-Analysis

Directory of Open Access Journals (Sweden)

Chakrapani Balijepalli

2018-01-01

Full Text Available Background. Treatment of schizophrenia with first- and second-generation antipsychotics has been associated with elevated prolactin levels, which may increase the risk for prolactin-related adverse events. Methods. Randomized controlled trials (RCTs included in a recent systematic review were considered for this analysis. A Bayesian network meta-analysis was used to compare changes in prolactin levels in pediatric patients diagnosed with schizophrenia or schizophrenia spectrum disorders treated with second-generation antipsychotics (SGAs. Results. Five RCTs, including 989 patients combined, have evaluated the changes in prolactin for pediatric patients after 6 weeks of treatment with risperidone, quetiapine, aripiprazole, olanzapine, and paliperidone. In the overall study population, treatment with risperidone was associated with the highest increase in mean prolactin levels compared to other SGAs. Patients treated with risperidone 4–6 mg/day were found to experience the greatest increases (55.06 ng/ml [95% CrI: 40.53–69.58] in prolactin levels, followed by risperidone 1–3 mg/day, paliperidone 3–6 mg/day, and paliperidone 6–12 mg/day. Conclusions. This study shows that there are differences in SGAs ability to cause hyperprolactinemia. Further, there is clear evidence of safety concerns with risperidone and paliperidone treatment in adolescent schizophrenia patients. Registration. PROSPERO CRD42014009506.

Histaminergic regulation of prolactin secretion

DEFF Research Database (Denmark)

Knigge, U P

1990-01-01

Histamine (HA), which acts as a neurotransmitter in the central nervous system, participates in the neuroendocrine regulation of prolactin (PRL) secretion. HA has a predominant stimulatory effect which is mediated via H2-receptors following central administration and via H1-receptors following...... systemic infusion of the amine. In addition, HA seems to exert a minor inhibitory effect on PRL secretion, an effect unmasked only during blockade of the receptor mediating the stimulatory effect. Following central administration the inhibitory effect is mediated via H1-receptors, while following systemic...... administration this effect is mediated via H2-receptors. In accordance with these findings, the H2-receptor antagonist cimetidine (CIM) has an inhibitory (following central administration) or stimulatory (following systemic administration) effect on PRL secretion. However, high doses of CIM possess an additional...

Cortisol rapidly reduces prolactin release and cAMP and 45Ca2+ accumulation in the cichlid fish pituitary in vitro

International Nuclear Information System (INIS)

Borski, R.J.; Helms, L.M.H.; Richman, N.H. III; Grau, E.G.

1991-01-01

During in vitro incubation, prolactin release is inhibited in a dose-related manner by cortisol. This action is mimicked by the synthetic glucocorticoid agonist dexamethasone but not by other steroids tested. Perifusion studies indicate that the inhibition of [ 3 H]prolactin release by cortisol occurs within 20 min. Cortisol (50 nM) also inhibits cAMP accumulation and reduces 45 Ca 2+ accumulation in the tilapia rostral pars distalis within 15 min. Cortisol's action on prolactin release is blocked in the presence of either the Ca 2+ ionophore A23187 or a combination of dibutyryl cAMP and 3-isobutyl-1-methylxanthine, which increase intracellular Ca 2+ and cAMP, respectively. Taken together, these findings suggest that cortisol may play a physiologically relevant role in the rapid modulation of prolactin secretion in vivo. These studies also suggest that the inhibition of prolactin release by cortisol is a specific glucocorticoid action that may be mediated, in part, through cortisol's ability to inhibit intracellular cAMP and Ca 2+ metabolism

Prolactin-stimulated mitogenesis in the Nb2 rat lymphoma cell: Lack of protoporphyrin IX effects

Energy Technology Data Exchange (ETDEWEB)

Gerrish, K.E.; Putnam, C.W.; Laird, H.E. II (Univ. of Arizona, Tucson (USA))

1990-01-01

Pharmacological characterization of the Nb2 cell peripheral-type benzodiazepine receptor (PBR) was determined using selected 1,4-benzodiazepines, PK 11195, and protoporphyrin IX (PPIX) to compete for specific ({sup 3}H) Ro5-4864 binding. These data suggest that PPIX possesses an affinity for the Nb2 cell PBR. We have previously reported that the peripheral benzodiazepine ligands, Ro5-4864 and PK 11195, modulate prolactin-stimulated mitogenesis in the Nb2 cell. In contrast, PPIX, a putative endogenous ligand for the PBR had no effect on prolactin-stimulated mitogenesis in the Nb2 cell over the concentration range from 10{sup {minus}15} M to 10{sup {minus}6} M. Taken together these data show that PPIX has an affinity for the Nb2 cell PBR but does not modulate prolactin-stimulated mitogenesis at concentrations which should bind to the Nb2 cell PBR.

Serum prolactin revisited: parametric reference intervals and cross platform evaluation of polyethylene glycol precipitation-based methods for discrimination between hyperprolactinemia and macroprolactinemia.

Science.gov (United States)

Overgaard, Martin; Pedersen, Susanne Møller

2017-10-26

Hyperprolactinemia diagnosis and treatment is often compromised by the presence of biologically inactive and clinically irrelevant higher-molecular-weight complexes of prolactin, macroprolactin. The objective of this study was to evaluate the performance of two macroprolactin screening regimes across commonly used automated immunoassay platforms. Parametric total and monomeric gender-specific reference intervals were determined for six immunoassay methods using female (n=96) and male sera (n=127) from healthy donors. The reference intervals were validated using 27 hyperprolactinemic and macroprolactinemic sera, whose presence of monomeric and macroforms of prolactin were determined using gel filtration chromatography (GFC). Normative data for six prolactin assays included the range of values (2.5th-97.5th percentiles). Validation sera (hyperprolactinemic and macroprolactinemic; n=27) showed higher discordant classification [mean=2.8; 95% confidence interval (CI) 1.2-4.4] for the monomer reference interval method compared to the post-polyethylene glycol (PEG) recovery cutoff method (mean=1.8; 95% CI 0.8-2.8). The two monomer/macroprolactin discrimination methods did not differ significantly (p=0.089). Among macroprolactinemic sera evaluated by both discrimination methods, the Cobas and Architect/Kryptor prolactin assays showed the lowest and the highest number of misclassifications, respectively. Current automated immunoassays for prolactin testing require macroprolactin screening methods based on PEG precipitation in order to discriminate truly from falsely elevated serum prolactin. While the recovery cutoff and monomeric reference interval macroprolactin screening methods demonstrate similar discriminative ability, the latter method also provides the clinician with an easy interpretable monomeric prolactin concentration along with a monomeric reference interval.

MATERNAL EXPOSURE TO ATRAZINE DURING LACTATION SUPPRESSES SUCKLING-INDUCED PROLACTIN RELEASE AND RESULTS IN PROSTATITIS IN THE ADULT OFFSPRING

Science.gov (United States)

The availability of prolactin (PRL) to the neonatal brain is known to affect the development of the tuberoinfundibular (TIDA) neurons and, as a consequence, lead to alterations in subsequent PRL regulation. Without early lactational exposure to PRL (derived from the dam's milk), ...

Serum Prolactin in Diagnosis of Epileptic Seizures

Directory of Open Access Journals (Sweden)

J Gordon Millichap

2005-09-01

Full Text Available The results of studies in databases and references concerning serum prolactin levels (PRL in patients with suspected seizures were rated for quality and analyzed by members of the Therapeutics Subcommittee of the American Academy of Neurology.

Radioimmunoassay of human homologous prolactin in serum with commercially available reagents

International Nuclear Information System (INIS)

Kao, P.C.; Jiang, N.S.; Abboud, C.F.

1977-01-01

A clinically useful and reproducible radioimmunoassay for human homologous prolactin, established with commercially available reagents, was studied and validated. We present detailed conditions for iodination and purification of labeled prolactin and the optimal conditions for the assay. By the method, we found values (μg/liter) as follows for serum prolactin: normal men, 8.9 +- 5.2 (mean +- SD); normal women, 11.8 +- 5.5; normal women taking contraceptive pills, 9.2 +- 5.0; pregnant women in the third trimester, 188 +- 69.5; patients with various diseases other than of the hypothalamic-pituitary axis, 9.3 +- 6.3; in some patients with amenorrhea and galactorrhea of diverse origin, 78.2 +- 87.4; and in some patients with surgically proven pituitary tumor, 1414 +- 1980. Results under provocative testing are also presented for a patient with normal hypothalamic-pituitary function

Region-specific expression and hormonal regulation of the first exon variants of rat prolactin receptor mRNA in rat brain and anterior pituitary gland.

Science.gov (United States)

Nogami, H; Hoshino, R; Ogasawara, K; Miyamoto, S; Hisano, S

2007-08-01

Recent studies have revealed the occurrence of five first exon variants of the rat prolactin receptor mRNA, suggesting that multiple promoters direct prolactin receptor transcription in response to different regulatory factors. In the present study, regional expression of these first exon variants, as well as two prolactin receptor subtypes generated by alternative splicing, was examined in the brains and anterior pituitary glands of female rats. Expression of the long-form was detected in the choroid plexus, hypothalamus, hippocampus, cerebral cortex and anterior pituitary gland, whereas the short form was detected only in the choroid plexus. E1-3 mRNA, a first exon variant, was detected in the choroid plexus, hypothalamus, and anterior pituitary gland, whereas E1-4 was detected only in the choroid plexus. Other variants were not detectable by the polymerase chain reaction protocol employed in this study. Ovariectomy increased the short form in the choroid plexus and the E1-3 expression in the choroid plexus and pituitary gland, but changes in the long-form and E1-4 expression were minimal. Replacement of oestrogens and prolactin suggest that oestrogens down-regulate E1-3 expression in the choroid plexus and pituitary gland, and that the negative effect of oestrogen is mediated by prolactin in the pituitary gland. The present results revealed the region-specific promoter usage in prolactin receptor mRNA transcription, as well as the involvement of oestrogens in the regulation of E1-3 mRNA expression in the brain and pituitary gland.

Dedicated EGR engine with dynamic load control

Science.gov (United States)

Hayman, Alan W.; McAlpine, Robert S.; Keating, Edward J.

2016-09-06

An internal combustion engine comprises a first engine bank and a second engine bank. A first intake valve is disposed in an intake port of a cylinder of the first engine bank, and is configured for metering the first flow of combustion air by periodically opening and closing according to a first intake valve lift and duration characteristic. A variable valve train control mechanism is configured for affecting the first intake valve lift and duration characteristic. Either a lift or duration of the first intake valve is modulated so as to satisfy an EGR control criterion.

Ankaferd Blood Stopper induces apoptosis and regulates PAR1 and ...

African Journals Online (AJOL)

Mine Mumcuoglu

2014-12-16

Dec 16, 2014 ... investigated for its properties. However there are no ... types of proteins and factors acting on cellular functions such as protein-2 (AP2), ... ATF1), cyclic AMP response element binding protein (CREB),. E2F1–5, E2F6, EGR, ...

Studi Experimental Penggunaan Venturi Scrubber dan Cyclonic Separator Untuk Meningkatkan Kinerja pada Sistem Exhaust Gas Recirculation (EGR dalam Menurunkan NOX pada Motor Diesel

Directory of Open Access Journals (Sweden)

Samsu Dlukha N

2012-09-01

Full Text Available Salah satu cara yang efektif untuk mengurangi NOX adalah dengan menggunakan metode Exhaust Gas Recirculation (EGR. Dengan metode EGR, oksigen yang masuk ke ruang bakar akan berkurang sehingga NOX dapat diturunkan dengan signifikan, akan tetapi power dari mesin tersebut juga akan berkurang dan Particulate Matter (PM akan naik secara signifikan. Dalam penelitian ini dibahas penggunaan EGR yang telah di optimalkan dengan penambahan venturi scrubber dan cyclonic separator, tujuannya mengurangi NOX tanpa meningkatkan PM. Hasil pengujian menunjukkan NOX turun sebesar 48.89% dan PM turun dari 69,87%  menjadi 9.87%.

21 CFR 862.1625 - Prolactin (lactogen) test system.

Science.gov (United States)

2010-04-01

... anterior pituitary gland or of the hypothalamus portion of the brain. (b) Classification. Class I (general... system is a device intended to measure the anterior pituitary polypeptide hormone prolactin in serum and...

Sex differences in the relationship between prolactin levels and impaired processing speed in early psychosis.

Science.gov (United States)

Montalvo, Itziar; Nadal, Roser; Armario, Antonio; Gutiérrez-Zotes, Alfonso; Creus, Marta; Cabezas, Ángel; Solé, Montse; Algora, Maria José; Sánchez-Gistau, Vanessa; Vilella, Elisabet; Labad, Javier

2018-06-01

Hyperprolactinaemia is commonly observed in people with psychotic disorders due to D2 receptor blockade by antipsychotic drugs, although it may also exist in drug-naïve patients with first-episode psychosis. Recent studies suggest that hyperprolactinaemia may have a negative impact on cognitive function in people with early psychosis. We aimed to explore whether there are sex differences in the association between prolactin levels and cognitive performance in early psychosis patients. We studied 60 young patients with early psychosis (aged 18-35 years, 35% females) and a sex- and age-matched control group of 50 healthy subjects. Cognitive assessment was performed with the MATRICS Consensus Cognitive Battery. Prolactin, total cortisol, follicular-stimulating hormone, luteal hormone and sex steroids (testosterone in men, oestradiol and progesterone in women) were measured in plasma. Salivary cortisol was measured at different sampling times (awakening response, 10:00 and 23:00). Psychopathological status was assessed, and antipsychotic treatment was registered. Multiple linear regression analyses were used to explore the relationship between prolactin and cognitive tasks while adjusting for covariates. Prolactin levels were associated with impaired processing speed in men, and this association was independent of cortisol and testosterone. In women, prolactin levels were not associated with processing speed tasks, although we observed a negative effect of prolactin on verbal learning and spatial working memory in female healthy subjects. The male-dependent effect maintained its significance after adjusting for education status, antipsychotic treatment and negative symptoms. Our study demonstrates that the previously reported association between high prolactin levels and impaired cognitive processes in early psychosis is restricted to men.

Evaluation of the Correlation Coefficient of Polyethylene Glycol Treated and Direct Prolactin Results and Comparability with Different Assay System Results.

Science.gov (United States)

Pal, Shyamali

2017-12-01

The presence of Macro prolactin is a significant cause of elevated prolactin resulting in misdiagnosis in all automated systems. Poly ethylene glycol (PEG) pretreatment is the preventive process but such process includes the probability of loss of a fraction of bioactive prolactin. Surprisingly, PEG treated EQAS & IQAS samples in Cobas e 411 are found out to be correlating with direct results of at least 3 immunoassay systems and treated and untreated Cobas e 411 results are comparable by a correlation coefficient. Comparison of EQAS, IQAS and patient samples were done to find out the trueness of such correlation factor. Study with patient's results have established the correlation coefficient is valid for very small concentration of prolactin also. EQAS, IQAS and 150 patient samples were treated with PEG and prolactin results of treated and untreated samples obtained from Roche Cobas e 411. 25 patient's results (treated) were compared with direct results in Advia Centaur, Architect I & Access2 systems. Correlation coefficient was obtained from trend line of the treated and untreated results. Two tailed p-value obtained from regression coefficient(r) and sample size. The correlation coefficient is in the range (0.761-0.771). Reverse correlation range is (1.289-1.301). r value of two sets of calculated results were 0.995. Two tailed p- value is zero approving dismissal of null hypothesis. The z-score of EQAS does not always assure authenticity of resultsPEG precipitation is correlated by the factor 0.761 even in very small concentrationsAbbreviationsGFCgel filtration chromatographyPEGpolyethylene glycolEQASexternal quality assurance systemM-PRLmacro prolactinPRLprolactinECLIAelectro-chemiluminescence immunoassayCLIAclinical laboratory improvement amendmentsIQASinternal quality assurance systemrregression coefficient.

Selective serotonin reuptake inhibitor (SSRI antidepressants, prolactin and breast cancer

Directory of Open Access Journals (Sweden)

Janet eAshbury

2012-12-01

Full Text Available Selective serotonin reuptake inhibitors (SSRIs are a widely prescribed class of anti-depressants. Laboratory and epidemiologic evidence suggests that a prolactin-mediated mechanism secondary to increased serotonin levels at neuronal synapses could lead to a potentially carcinogenic effect of SSRIs. In this population-based case-control study, we evaluated the association between SSRI use and breast cancer risk as a function of their relative degree of inhibition of serotonin reuptake as a proxy for their impact on prolactin levels. Cases were 2,129 women with primary invasive breast cancer diagnosed from 2003-2007, and controls were 21,297 women randomly selected from the population registry. Detailed information for each SSRI prescription dispensed was compiled using the Saskatchewan prescription database. Logistic regression was used to evaluate the impact of use of high and lower inhibitors of serotonin reuptake and duration of use, as well as to assess the effect of individual high inhibitors on the risk of breast cancer. Exclusive users of high or lower inhibitors of serotonin reuptake were not at increased risk for breast cancer compared with nonusers of SSRIs (OR = 1.01, CI = 0.88-1.17 and OR = 0.91, CI = 0.67-1.25 respectively, regardless of their duration of use or menopausal status. While we cannot rule out the possibility of a clinically important risk increase (OR = 1.83, CI = 0.99-3.40 for long-term users of sertraline (≥24 prescriptions, given the small number of exposed cases (n=12, the borderline statistical significance and the wide confidence interval, these results need to be interpreted cautiously. In this large population-based case-control study, we found no conclusive evidence of breast cancer risk associated with the use of SSRIs even after assessing the degree of serotonin reuptake inhibition and duration of use. Our results do not support the serotonin-mediated pathway for the prolactin-breast cancer hypothesis.

Potentials of cooled EGR and water injection for knock resistance and fuel consumption improvements of gasoline engines

International Nuclear Information System (INIS)

Bozza, Fabio; De Bellis, Vincenzo; Teodosio, Luigi

2016-01-01

Highlights: • 1D simulation of a turbocharged VVA engine under knock limited operation. • Description of turbulence, combustion and knock by phenomenological models. • Comparison of EGR and ported water injection at high load for knock mitigation and fuel economy. • Virtual calibration of engine control parameters by a 1D model. - Abstract: It is well known that the downsizing philosophy allows the improvement of the brake specific fuel consumption (BSFC) at part load operation for spark ignition (SI) engines. On the other hand, the BSFC is penalized at high load because of the knock occurrence and of further limitations on the turbine inlet temperature (TIT). Knock control forces the adoption of a late combustion phasing, causing a deterioration of the thermodynamic efficiency, while the TIT control requires the enrichment of the air-to-fuel ratio (A/F), with additional BSFC drawbacks. In this work, two promising techniques are investigated by a 1D approach with the aim of improving the fuel economy of a turbocharged SI engine at full load knock-limited operation. The first technique is the recirculation of low-pressure cooled exhaust gas (EGR), while the second is the injection of liquid water at the intake ports. Proper “in-house developed” sub-models are used to describe the turbulence, combustion and knock phenomena. The effects of the above techniques are studied in six operating points at full load and different speeds for various A/F levels and inert content, by varying the EGR rate and water-to-fuel ratio. The presented results highlight that both the solutions involve significant BSFC improvements, especially in the operating conditions at medium engine speeds. In fact, the introduction of inert gas in the cylinder contributes to reduce the knock tendency, resulting in the possibility to advance the combustion phasing and reduce, or even avoid, the mixture over-fuelling. The heat subtracted by the water evaporation enhances the above effects

Prolactin 177, prolactin 188, and extracellular osmolality independently regulate the gene expression of ion transport effectors in gill of Mozambique tilapia.

Science.gov (United States)

Inokuchi, Mayu; Breves, Jason P; Moriyama, Shunsuke; Watanabe, Soichi; Kaneko, Toyoji; Lerner, Darren T; Grau, E Gordon; Seale, Andre P

2015-11-15

This study characterized the local effects of extracellular osmolality and prolactin (PRL) on branchial ionoregulatory function of a euryhaline teleost, Mozambique tilapia (Oreochromis mossambicus). First, gill filaments were dissected from freshwater (FW)-acclimated tilapia and incubated in four different osmolalities, 280, 330, 380, and 450 mosmol/kg H2O. The mRNA expression of Na(+)/K(+)-ATPase α1a (NKA α1a) and Na(+)/Cl(-) cotransporter (NCC) showed higher expression with decreasing media osmolalities, while Na(+)/K(+)/2Cl(-) cotransporter 1a (NKCC1a) and PRL receptor 2 (PRLR2) mRNA levels were upregulated by increases in media osmolality. We then incubated gill filaments in media containing ovine PRL (oPRL) and native tilapia PRLs (tPRL177 and tPRL188). oPRL and the two native tPRLs showed concentration-dependent effects on NCC, NKAα1a, and PRLR1 expression; Na(+)/H(+) exchanger 3 (NHE3) expression was increased by 24 h of incubation with tPRLs. Immunohistochemical observation showed that oPRL and both tPRLs maintained a high density of NCC- and NKA-immunoreactive ionocytes in cultured filaments. Furthermore, we found that tPRL177 and tPRL188 differentially induce expression of these ion transporters, according to incubation time. Together, these results provide evidence that ionocytes of Mozambique tilapia may function as osmoreceptors, as well as directly respond to PRL to modulate branchial ionoregulatory functions. Copyright © 2015 the American Physiological Society.

A case of sibutramine-induced hyperprolactinemia.

Science.gov (United States)

Soares Leaes, Carolina Garcia; Pereira-Lima, Júlia Fernanda Semmelmann; da Costa Oliveira, Miriam

2011-01-01

Several drugs may cause hyperprolactinemia, especially antipsychotic drugs and prokynetic drugs. Serum prolactin concentrations increase within hours after acute administration of these drugs and return to normal within two to four days after cessation of chronic therapy. So far, sibutramine, a sympathomimetic drug used in the management of obesity, was not described to be associated with altered prolactin levels. The purpose of this study is to present a case of sibutramine-induced hiperprolactinemia. A 38-year-old white female patient seeks medical attention complaining of weight gain (Body mass index: 35) associated with anxiety. She started sibutramine treatment and presented with amenogalactorrhea. Hyperprolactinemia was diagnosed (prolactin of 46 and 89.6 ng/mL) with normal thyroid, renal and hepatic function, and a negative pregnancy test. A sella MRI was performed and sibutramine was suspended. Prolactin levels returned to normal within 15 days of sibutramine cessation and remained normal within 90 days of follow-up, with resolution of the amenogalactorrhea syndrome. sibutramine may be considered in differential diagnosis of drug-induced hyperprolactinemia.

Multidimensional modeling of the effect of Exhaust Gas Recirculation (EGR) on exergy terms in an HCCI engine fueled with a mixture of natural gas and diesel

International Nuclear Information System (INIS)

Jafarmadar, Samad; Nemati, Peyman; Khodaie, Rana

2015-01-01

Highlights: • The exergy efficiency decreases by 41.3%. • The irreversibility increases by 46.80%. • The cumulative heat loss exergy decreases by 68.10%. • The cumulative work exergy decreases by 63.4%. • The exhaust losses exergy increases by 28.79%. - Abstract: One of the most important issues in HCCI engines is auto-ignition timing control. EGR introduction into intake charge can be a method to control combustion phasing and its duration. In the current study, a FORTRAN-based code which includes 10 species (O_2, N_2, H_2O, CO_2, CO, H_2, OH, O, N, NO) associated with combustion products was employed to study the exergy analysis in a dual fuel (natural gas + diesel) HCCI engine at four EGR (exhaust gas recirculation) mass fractions (0%, 10%, 20%, and 30%) while the diesel fuel amount was held constant. In order to achieve this task, a 3-D CFD code was employed to model the energy balance during a closed cycle of running engine simulation. Moreover, an efficient Extend Coherent Flame Model-Three Zone model (ECFM-3Z) method was employed to analyze the combustion process. With crank positions at different EGR mass fractions, the exergy terms were identified and calculated separately. It was found that as EGR mass fraction increased from 0% to 30% (in 10% increment steps), exergy efficiency decreased from 48.9% to 28.7%. Furthermore, with the change in EGR mass fraction, the cumulative heat loss exergy decreased from 10.1% to 5.64% of mixture fuels chemical exergy.

Solid Phase Radioimmunoassay for Measuring Serum Prolactin Using Antibody Coupled Magnetizable Particles

International Nuclear Information System (INIS)

El-Bayoumy, A.S.A.

2012-01-01

The objective of the present work was to prepare solid phase radioimmunoassay (RIA) reagents. Development as well as optimization and validation of RIA system using solid phase magnetic particles for the measurement of prolactin (PRL) in human serum are described. The production of polyclonal antibodies was carried out by immunizing three Balb/C mice intraperitoneal through primary injection and two booster doses. Low density magnetizable cellulose iron oxide particles have been used to couple covalently to the IgG fraction of polyclonal anti-prolactin using carbonyl diimidazole activation method and applied as a solid phase separating agent for RIA of serum prolactin. Preparation of 125 I-PRL tracer was prepared using lactoperoxidase method and it was purified by gel filtration using sephadex G-100. The PRL standards were prepared using a highly purified PRL antigen with assay buffer as standard matrix. Optimization and validation of the assay were carried out. The results obtained provide a low cost, simple, sensitive, specific and accurate RIA system of prolactin based on magnetizable solid phase separation. These magnetic particles retain their characteristics during storage for 6 months at 4 degree C. In conclusion, this assay could be used as a useful diagnostic tool for pituitary dysfunction and possible reproductive disability.

Growth hormone, prolactin and cortisol response to exercise in patients with depression

DEFF Research Database (Denmark)

Krogh, Jesper; Nordentoft, Merete; Mohammad-Nezhad, Mahdi

2010-01-01

BACKGROUND: A blunted growth hormone and prolactin response to pharmacological stress test have previously been found in depressed patients, as well as an increased cortisol response to psychosocial stress. This study investigated these hormones in response to acute exercise using an incremental...... bicycle test. METHOD: A cross-sectional comparison of cortisol, growth hormone, and prolactin in depressed (n=137) and healthy (n=44) subjects during rest and in response to an incremental bicycle test. Secondly, we tested the depressed patients again after a 4-month randomized naturalistic exercise...... intervention. RESULTS: Resting plasma levels of growth hormone (GH), cortisol, or prolactin (PRL) did not differ between depressed and healthy subjects (all p-values>.12). In response to an incremental bicycle test the GH (p=.02) and cortisol (p=.05) response in depressed was different compared to healthy...

Inhibition of growth hormone and prolactin secretion by a serine proteinase inhibitor

International Nuclear Information System (INIS)

Rappay, G.; Nagy, I.; Makara, G.B.; Horvath, G.; Karteszi, M.; Bacsy, E.; Stark, E.

1984-01-01

The action of the tripeptide aldehyde t-butyloxycarbonyl-DPhe-Pro-Arg-H (boc-fPR-H), belonging to a family of serine proteinase inhibitors, on the release of immunoreactive prolactin (iPRL) and growth hormone (iGH) has been studied. In rat anterior pituitary cell cultures and pituitary quarters 1 mM boc-fPR-H inhibited basal iPRL and iGH release. Thyroliberin-induced iPRL release by cultured cells was also markedly inhibited with a concomitant accumulation of intracellular iPRL. During the short- and long-term exposure of cells to boc-fPR-H there were no changes in total cell protein contents and in activities of some lysosomal marker enzymes. The marked inhibition of basal as well as stimulated hormone release in the presence of the enzyme inhibitor might suggest that at least a portion of the hormones is released via a proteolytic enzyme-dependent process

Expression of immediate-early genes in the dorsal cochlear nucleus in salicylate-induced tinnitus.

Science.gov (United States)

Hu, Shou-Sen; Mei, Ling; Chen, Jian-Yong; Huang, Zhi-Wu; Wu, Hao

2016-02-01

Spontaneous neuronal activity in dorsal cochlear nucleus (DCN) may be involved in the physiological processes underlying salicylate-induced tinnitus. As a neuronal activity marker, immediate-early gene (IEG) expression, especially activity-dependent cytoskeletal protein (Arc/Arg3.1) and the early growth response gene-1 (Egr-1), appears to be highly correlated with sensory-evoked neuronal activity. However, their relationships with tinnitus induced by salicylate have rarely been reported in the DCN. In this study, we assessed the effect of acute and chronic salicylate treatment on the expression of N-methyl D-aspartate receptor subunit 2B (NR2B), Arg3.1, and Egr-1. We also observed ultrastructural alterations in the DCN synapses in an animal model of tinnitus. Levels of mRNA and protein expression of NR2B and Arg3.1 were increased in rats that were chronically administered salicylate (200 mg/kg, twice daily for 3, 7, or 14 days). These levels returned to baseline 14 days after cessation of treatment. However, no significant changes were observed in Egr-1 gene expression in any groups. Furthermore, rats subjected to long-term salicylate administration showed more presynaptic vesicles, thicker and longer postsynaptic densities, and increased synaptic interface curvature. Alterations of Arg3.1 and NR2B may be responsible for the changes in the synaptic ultrastructure. These changes confirm that salicylate can cause neural plasticity changes at the DCN level.

Cyclical Changes in Prolactin Levels among Infertile Women ...

African Journals Online (AJOL)

Michael Horsfall

investigation of infertility while the elevation of prolactin in the 3 study groups might be responsible for the infertility observed. ... dopamine and enhanced by some other hormones. In ... also appears to have a role in the immune response,.

The post-orgasmic prolactin increase following intercourse is greater than following masturbation and suggests greater satiety.

Science.gov (United States)

Brody, Stuart; Krüger, Tillmann H C

2006-03-01

Research indicates that prolactin increases following orgasm are involved in a feedback loop that serves to decrease arousal through inhibitory central dopaminergic and probably peripheral processes. The magnitude of post-orgasmic prolactin increase is thus a neurohormonal index of sexual satiety. Using data from three studies of men and women engaging in masturbation or penile-vaginal intercourse to orgasm in the laboratory, we report that for both sexes (adjusted for prolactin changes in a non-sexual control condition), the magnitude of prolactin increase following intercourse is 400% greater than that following masturbation. The results are interpreted as an indication of intercourse being more physiologically satisfying than masturbation, and discussed in light of prior research reporting greater physiological and psychological benefits associated with coitus than with any other sexual activities.

Metabolic and stress-related roles of prolactin-releasing peptide.

Science.gov (United States)

Onaka, Tatsushi; Takayanagi, Yuki; Leng, Gareth

2010-05-01

In the modern world, improvements in human health can be offset by unhealthy lifestyle factors, including the deleterious consequences of stress and obesity. For energy homeostasis, humoral factors and neural afferents from the gastrointestinal tract, in combination with long-term nutritional signals, communicate information to the brain to regulate energy intake and expenditure. Energy homeostasis and stress interact with each other, and stress affects both food intake and energy expenditure. Prolactin-releasing peptide, synthesized in discrete neuronal populations in the hypothalamus and brainstem, plays an important role in integrating these responses. This review describes how prolactin-releasing peptide neurons receive information concerning both internal metabolic states and environmental conditions, and play a key role in energy homeostasis and stress responses. 2010 Elsevier Ltd. All rights reserved.

Serum prolactin concentrations in relation to hypopituitarism and obesity in children with optic nerve hypoplasia.

Science.gov (United States)

Vedin, Amy M; Garcia-Filion, Pamela; Fink, Cassandra; Borchert, Mark; Geffner, Mitchell E

2012-01-01

The majority of children with optic nerve hypoplasia (ONH) develop hypopituitarism and many also become obese. These associated conditions are a major cause of morbidity and are possibly due to hypothalamic dysfunction. Because mild hyperprolactinemia often occurs in subjects with disorders of the hypothalamus, we examined whether hyperprolactinemia was present in children with ONH during the first 3 years of life and whether it was a marker for hypopituitarism and/or obesity. Data were retrospectively analyzed from a registry study of children with ONH. The initial serum prolactin was obtained prior to age 36 months (n = 125) and compared with pituitary function and body mass index at age 5. 72% of subjects had an elevated initial serum prolactin and 60% had hypopituitarism. An elevated initial prolactin was associated with hypopituitarism (OR 2.58; 95% CI 1.16, 5.73), specifically with growth hormone deficiency (OR 2.77; 95% CI 1.21, 6.34). 31% of subjects had a body mass index ≥ 85th percentile, but this did not correlate with initial hyperprolactinemia. Early hyperprolactinemia correlates with the presence of hypopituitarism in children with ONH, but it is not a reliable prognosticator of hypopituitarism. Additionally, hyperprolactinemia does not predict future weight excess. Copyright © 2012 S. Karger AG, Basel.

Enhanced efficacy of radiation-induced gene therapy in mice bearing lung adenocarcinoma xenografts using hypoxia responsive elements

International Nuclear Information System (INIS)

Wang Wei-dong; Chen Zheng-tang; Li De-zhi; Duan Yu-zhong; Cao Zheng-huai; Li Rong

2005-01-01

The aim of the present study was to investigate whether the hypoxia responsive element (HRE) could be used to enhance suicide gene (HSV-tk) expression and tumoricidal activity in radiation-controlled gene therapy of human lung adenocarcinoma xenografts. A chimeric promoter, HRE-Egr, was generated by directly linking a 0.3-kb fragment of HRE to a 0.6-kb human Egr-1 promoter. Retroviral vectors containing luciferase or the HSV-tk gene driven by Egr-1 or HRE-Egr were constructed. A human adenocarcinoma cell line (A549) was stably transfected with the above vectors using the lipofectamine method. The sensitivity of transfected cells to prodrug ganciclovir (GCV) and cell survival rates were analyzed after exposure to a dose of 2 Gy radiation and hypoxia (1%). In vivo, tumor xenografts in BALB/c mice were transfected with the constructed retroviruses and irradiated to a total dose of 6 Gy, followed by GCV treatment (20 mg/kg for 14 days). When the HSV-tk gene controlled by the HRE-Egr promoter was introduced into A549 cells by a retroviral vector, the exposure to 1% O 2 and 2 Gy radiation induced significant enhancement of GCV cytotoxicity to the cells. Moreover, in nude mice bearing solid tumor xenografts, only the tumors infected with the hybrid promoter-containing virus gradually disappeared after GCV administration and radiation. These results indicate that HRE can enhance transgene expression and tumoricidal activity in HSV-tk gene therapy controlled by ionizing radiation in hypoxic human lung adenocarcinoma. (author)

Neuroendocrine response to film-induced sexual arousal in men and women.

Science.gov (United States)

Exton, N G; Truong, T C; Exton, M S; Wingenfeld, S A; Leygraf, N; Saller, B; Hartmann, U; Schedlowski, M

2000-02-01

The psychoneuroendocrine responses to sexual arousal have not been clearly established in humans. However, we have demonstrated previously that masturbation-induced orgasm stimulates cardiovascular activity and induces increases in catecholamines and prolactin in blood of both males and females. We presently investigated the role of orgasm in producing these effects. Therefore, in this study parallel analysis of prolactin, adrenaline, noradrenaline, and cortisol concentrations, together with cardiovascular variables of systolic/diastolic blood pressure and heart rate were undertaken during film-induced sexual arousal in nine healthy adult men and nine healthy adult women. Blood was drawn continuously via an indwelling cannula and connected tubing system passed through a mini-pump. In parallel, the cardiovascular parameters were recorded continuously via a computerised finger-cuff sensor. Subjective sexual arousal increased significantly in both men and women during the erotic film, with sexual arousal eliciting an increase in blood pressure in both males and females, and plasma noradrenaline in females only. In contrast, adrenaline, cortisol and prolactin levels were unaffected by sexual arousal. These data further consolidate the role of sympathetic activation in sexual arousal processes. Furthermore, they demonstrate that increases in plasma prolactin during sexual stimulation are orgasm-dependent, suggesting that prolactin may regulate a negative-feedback sexual-satiation mechanism.

Chronic ciguatoxin treatment induces synaptic scaling through voltage gated sodium channels in cortical neurons.

Science.gov (United States)

Martín, Víctor; Vale, Carmen; Rubiolo, Juan A; Roel, Maria; Hirama, Masahiro; Yamashita, Shuji; Vieytes, Mercedes R; Botana, Luís M

2015-06-15

Ciguatoxins are sodium channels activators that cause ciguatera, one of the most widespread nonbacterial forms of food poisoning, which presents with long-term neurological alterations. In central neurons, chronic perturbations in activity induce homeostatic synaptic mechanisms that adjust the strength of excitatory synapses and modulate glutamate receptor expression in order to stabilize the overall activity. Immediate early genes, such as Arc and Egr1, are induced in response to activity changes and underlie the trafficking of glutamate receptors during neuronal homeostasis. To better understand the long lasting neurological consequences of ciguatera, it is important to establish the role that chronic changes in activity produced by ciguatoxins represent to central neurons. Here, the effect of a 30 min exposure of 10-13 days in vitro (DIV) cortical neurons to the synthetic ciguatoxin CTX 3C on Arc and Egr1 expression was evaluated using real-time polymerase chain reaction approaches. Since the toxin increased the mRNA levels of both Arc and Egr1, the effect of CTX 3C in NaV channels, membrane potential, firing activity, miniature excitatory postsynaptic currents (mEPSCs), and glutamate receptors expression in cortical neurons after a 24 h exposure was evaluated using electrophysiological and western blot approaches. The data presented here show that CTX 3C induced an upregulation of Arc and Egr1 that was prevented by previous coincubation of the neurons with the NaV channel blocker tetrodotoxin. In addition, chronic CTX 3C caused a concentration-dependent shift in the activation voltage of NaV channels to more negative potentials and produced membrane potential depolarization. Moreover, 24 h treatment of cortical neurons with 5 nM CTX 3C decreased neuronal firing and induced synaptic scaling mechanisms, as evidenced by a decrease in the amplitude of mEPSCs and downregulation in the protein level of glutamate receptors that was also prevented by tetrodotoxin

Simulation and control of a HD diesel engine equipped with new EGR technology

NARCIS (Netherlands)

Dekker, H.J.; Sturm, W.L.

1996-01-01

A dynamic model of a Heavy Duty (HD) turbocharged and aftercooled diesel engine was developed. The engine was equipped with high pressure diesel injection, a Variable Geometry Turbine (VGT) and an Exhaust Gas Recirculation (EGR) system. This engine was targeted at meeting EURO4 emission

Effects of photoperiod and temperature on the release of prolactin from the pituitary gland of the goldfish, Carassius auratus L

Energy Technology Data Exchange (ETDEWEB)

McKeown, B.A. (Simon Fraser Univ., Burnaby, BC); Peter, R.E.

1976-11-01

A number of experiments were conducted to investigate the effects of photoperiod and temperature on prolactin release from the goldfish pituitary gland. Fish were acclimated to different photoperiods and temperatures, and also were subjected to a change in either of these two parameters after different acclimation conditions. Serum and pituitary samples were collected and analyzed by radioimmunoassay for prolactin levels. In other experiments samples for prolactin analysis were taken every 3 h intermittently over a period of 3 days from fish that were acclimated to different photoperiod and temperature conditions. Longer photoperiods and higher temperatures caused pituitary prolactin release. Serum prolactin changed on a circadian rhythm and the rhythm was modified depending on the length of the photoperiod.

Emission characteristics of multiple stage diesel combustion. Effect of exhaust gas recirculation; Nidan nensho diesel kikan no haishutsubutsu tokusei. EGR no eikyo

Energy Technology Data Exchange (ETDEWEB)

Hashizume, T.; Miyamoto, T.; Akagawa, H.; Tsujimura, K. [New A.C.E. Institute Co. Ltd., Tokyo (Japan)

1998-05-01

For an aim to reduce NOx emission from diesel engines, it has become possible to realize it with smoke emission maintained at low levels by taking the following steps: initial combustion is carried out as lean pre-mixed combustion by adopting early fuel injection; the fuel is injected again after completion of this combustion; and EGR is combined with two-stage combustion which performs diffusion combustion under high temperature atmosphere. When a large quantity of EGR is used, cylinder temperature drops to have ignition timing delayed in the first stage, serving for improving fuel consumption. The problem of increase in smoke generation is solved by optimizing the injection timing at the second stage to suppress smoke generation increase, resulting in realization of lower NOx emission. By completing the second-stage fuel injection before ignition of the first-stage injection, it was possible to realize further lower NOx emission. Smoke increase due to higher EGR ratio was suppressed by pre-mixing both fuels injected in the first and second stages, although this is a high load operation. In addition, oxygen concentration and cylinder temperature were reduced, the gas pre-mixture was homogenized, and combustion velocity was suppressed by delaying the angle of ignition timing. This made low smoke combustion at {lambda} = 1 possible even in compressed ignition combustion. 8 refs., 12 figs., 1 tab.

Measurement by radioimmunoassay of casein content in rabbit mammary gland during pregnancy and after prolactin stimulation in organ culture

International Nuclear Information System (INIS)

Jahn, G.; Dusanter-Fourt, I.; Kelly, P.A.; Houdebine, L.M.; Djiane, J.

1987-01-01

A specific homologous radioimmunoassay was developed to measure rabbit β-casein in rabbit mammary gland with a sensitivity of 0.5 ng/ml protein. It was used to measure casein concentration during pregnancy and in organ culture of mammary gland explants. Casein was detectable in virgin mammary glands, showed a small increase during the first half of pregnancy, increased more than 20-fold between Days 21 and 27, and diminished somewhat on the first days of lactation. After 24 hr of culture, mammary gland explants had no detectable casein, but the addition of increasing concentrations of prolactin to a culture medium which contained insulin (5 μg/ml) and cortisol (0.5 μg/ml) induced a regular increase in the casein content of the tissue. Casein started to increase when 10 ng/ml of prolactin was present and maximal values were achieved for 100 ng/ml of the hormone

Rhus javanica Gall Extract Inhibits the Differentiation of Bone Marrow-Derived Osteoclasts and Ovariectomy-Induced Bone Loss

Directory of Open Access Journals (Sweden)

Tae-Ho Kim

2016-01-01

Full Text Available Inhibition of osteoclast differentiation and bone resorption is a therapeutic strategy for the management of postmenopausal bone loss. This study investigated the effects of Rhus javanica (R. javanica extracts on bone marrow cultures to develop agents from natural sources that may prevent osteoclastogenesis. Extracts of R. javanica (eGr cocoons spun by Rhus javanica (Bell. Baker inhibited the osteoclast differentiation and bone resorption. The effects of aqueous extract (aeGr or 100% ethanolic extract (eeGr on ovariectomy- (OVX- induced bone loss were investigated by various biochemical assays. Furthermore, microcomputed tomography (µCT was performed to study bone remodeling. Oral administration of eGr (30 mg or 100 mg/kg/day for 6 weeks augmented the inhibition of femoral bone mineral density (BMD, bone mineral content (BMC, and other factors involved in bone remodeling when compared to OVX controls. Additionally, eGr slightly decreased bone turnover markers that were increased by OVX. Therefore, it may be suggested that the protective effects of eGr could have originated from the suppression of OVX-induced increase in bone turnover. Collectively, the findings of this study indicate that eGr has potential to activate bone remodeling by inhibiting osteoclast differentiation and bone loss.

Effects of a two-hour early awakening and of bright light exposure on plasma patterns of cortisol, melatonin, prolactin and testosterone in man.

Science.gov (United States)

Touitou, Y; Benoit, O; Foret, J; Aguirre, A; Bogdan, A; Clodoré, M; Touitou, C

1992-03-01

Bright light is a synchronizing agent that entrains human circadian rhythms and modifies various endocrine and neuroendocrine functions. The aim of the present study was to determine whether and how the exposure to a bright light stimulus during the 2 h following a 2 h earlier awakening could modify the disturbance induced by the the sleep deprivation on the plasma patterns of hormones whose secretion is sensitive to light and/or sleep, namely melatonin, prolactin, cortisol and testosterone. Six healthy and synchronized (lights on: 07.00-23.00) male students (22.5 +/- 1.1 years) with normal psychological profiles volunteered for the study in winter. The protocol consisted of a baseline control night (customary sleep schedule) followed by three shortened nights with a rising at 05.00 and a 2 h exposure to either dim light (50 lux; one week) or bright light (2000 lux; other week). Our study showed a phase advance of the circadian rhythm of plasma cortisol without significant modifications of the hormone mean or peak concentration. Plasma melatonin concentration decreased following bright light exposure, whereas no obvious modifications of plasma testosterone or prolactin patterns could be observed in this protocol.

Analysis of Oxygenated Component (butyl Ether) and Egr Effect on a Diesel Engine

Science.gov (United States)

Choi, Seung-Hun; Oh, Young-Taig

Potential possibility of the butyl ether (BE, oxygenates of di-ether group) was analyzed as an additives for a naturally aspirated direct injection diesel engine fuel. Engine performance and exhaust emission characteristics were analyzed by applying the commercial diesel fuel and oxygenates additives blended diesel fuels. Smoke emission decreased approximately 26% by applying the blended fuel (diesel fuel 80 vol-% + BE 20vol-%) at the engine speed of 25,000 rpm and with full engine load compared to the diesel fuel. There was none significant difference between the blended fuel and the diesel fuel on the power, torque, and brake specific energy consumption rate of the diesel engine. But, NOx emission from the blended fuel was higher than the commercial diesel fuel. As a counter plan, the EGR method was employed to reduce the NOx. Simultaneous reduction of the smoke and the NOx emission from the diesel engine was achieved by applying the BE blended fuel and the cooled EGR method.

Effect of Exhaust Gas Recirculation (EGR on the Performance Characteristics of a Direct Injection Multi Cylinders Diesel Engine

Directory of Open Access Journals (Sweden)

Khalil Ibrahim Abaas

2016-07-01

Full Text Available Owing  to  the  energy  crisis  and  pollution  problems  of  today  investigations  have  concentrated  on decreasing  fuel  consumption  and  on  lowering  the  concentration  of  toxic  components  in  combustion products by using exhaust gas after treatments methods like PM filters and EGR for NOx reduction. In this study, the combustion characteristics of diesel fuel were compared with that pr oduced from adding EGR at several percentages to air manifold. The tests were performed in a four-cylinder direct injection (DI diesel engine at constant engine speed (1500 rpm and variable loads (from no load to 86 kN/m2, the tests were repeated with constant load (77 kN/m2 and variable engine speeds (from 1250 to 3000 rpm.The experimental results showed that adding EGR to diesel engine provided significant reductions in brake power (bp, brake thermal efficiency and exhaust gas temperatures, while high increments in brake specific  fuel  consumption  (bsfc.  High  EGR  percentage  (as  30%  in  this  article  caused  an  11.7% reduction  in  brake  thermal  efficiency,  26.38%  reduction  in  exhaust  gas  temperatures  and  12.28%  in volumetric efficiency at full load conditions.

Serum Prolactin Levels in Patients with Major Depressive Disorder Receiving Selective Serotonin-Reuptake Inhibitor Monotherapy for 3 Months: A Prospective Study

OpenAIRE

Park, Young-Min

2017-01-01

Objective It is unclear whether selective serotonin-reuptake inhibitors (SSRIs) can significantly increase the prolactin level. The purpose of this study was to identify the relationship between the prolactin level and the administration of SSRIs such as escitalopram and sertraline. An additional purpose was to determine whether the elevation of prolactin differs between escitalopram and sertraline treatment. Methods Serum prolactin levels were measured at baseline and after 3 months in 23 pa...

Effect of Sulpirid on blood serum prolactin- and TSH-levels

International Nuclear Information System (INIS)

Foldes, J.; Gyertyanfi, G.; Borvendeg, J.

1979-01-01

Euthyreoid and hyperthyreoid women were subjected to examinations investigating the effect of a dopamine-antagonist (Sulpirid) on serum TSH and prolactin (LTH)-levels. For measurements of serum concentrations the following kits were used: prolactine: CIS; TSH: Ria-mat-TSH (Byk-Mallinkrodt); thyroxine: Tiopac T 4 (Amersham); triiodothyronine: Ria-mat-T 3 (Byk-Mallinkrodt). Sulpirid increased both the LTH and the TSH-levels. In case of hyperthyreosis the effect of Sulpirid on LTH-levels was less pronounced and it had no effect on serum-TSH at all. Pre-treatment with a dopamine-agonist (Bromocryptin) impeded the effect of Sulpirid. It is concluded that dopamine-receptors do have a role in the regulation of TSH-secretion in the hypophysis. (L.E.)

Growth hormone and prolactin responses during partial and whole body warm-water immersions.

Science.gov (United States)

Koska, J; Rovensky, J; Zimanova, T; Vigas, M

2003-05-01

To elucidate the role of core and skin thermoreceptors in the release of growth hormone (GH) and prolactin (PRL), a sequence of two experiments using whole-body (head-out) and partial (one forearm) hot water immersions was performed. Experiment 1: Nine healthy men were exposed to head-out and partial water immersions (25 min, 38-39 degrees C). Head-out immersion increased the core temperature (38.0 +/- 0.1 vs. 36.7 +/- 0.1 degrees C, P immersion the core temperature was slightly elevated (36.8 +/- 0.1 vs. 36.6 +/- 0.1, P immersed one forearm once in 39 degrees C and once in 38 degrees C water. The measurements were performed in 5-min intervals. The GH concentration increased gradually from the beginning of the immersions (min 10; 39 degrees C: 1.9 +/- 1.0 vs. 0.6 +/- 0.3 ng mL(-1), P Immersion in 38 degrees C water did not induce core temperature changes. Peripheral thermoreceptors are involved in GH release when the body is exposed to elevated environmental temperature while a substantial elevation of core temperature is a precondition of PRL release.

Effect of Exhaust Gas Recirculation (EGR) on the Performance Characteristics of a Direct Injection Multi Cylinders Diesel Engine

OpenAIRE

Khalil Ibrahim Abaas

2016-01-01

Owing  to  the  energy  crisis  and  pollution  problems  of  today  investigations  have  concentrated  on decreasing  fuel  consumption  and  on  lowering  the  concentration  of  toxic  components  in  combustion products by using exhaust gas after treatments methods like PM filters and EGR for NOx reduction. In this study, the combustion characteristics of diesel fuel were compared with that pr oduced from adding EGR at several percentages to air manifold. The tests were performed in a fo...

Tuning the brain for motherhood: prolactin-like central signalling in virgin, pregnant, and lactating female mice.

Science.gov (United States)

Salais-López, Hugo; Lanuza, Enrique; Agustín-Pavón, Carmen; Martínez-García, Fernando

2017-03-01

Prolactin is fundamental for the expression of maternal behaviour. In virgin female rats, prolactin administered upon steroid hormone priming accelerates the onset of maternal care. By contrast, the role of prolactin in mice maternal behaviour remains unclear. This study aims at characterizing central prolactin activity patterns in female mice and their variation through pregnancy and lactation. This was revealed by immunoreactivity of phosphorylated (active) signal transducer and activator of transcription 5 (pSTAT5-ir), a key molecule in the signalling cascade of prolactin receptors. We also evaluated non-hypophyseal lactogenic activity during pregnancy by administering bromocriptine, which suppresses hypophyseal prolactin release. Late-pregnant and lactating females showed significantly increased pSTAT5-ir resulting in a widespread pattern of immunostaining with minor variations between pregnant and lactating animals, which comprises nuclei of the sociosexual and maternal brain, including telencephalic (septum, nucleus of the stria terminalis, and amygdala), hypothalamic (preoptic, paraventricular, supraoptic, and ventromedial), and midbrain (periaqueductal grey) regions. During late pregnancy, this pattern was not affected by the administration of bromocriptine, suggesting it to be elicited mostly by non-hypophyseal lactogenic agents, likely placental lactogens. Virgin females displayed, instead, a variable pattern of pSTAT5-ir restricted to a subset of the brain nuclei labelled in pregnant and lactating mice. A hormonal substitution experiment confirmed that estradiol and progesterone contribute to the variability found in virgin females. Our results reflect how the shaping of the maternal brain takes place prior to parturition and suggest that lactogenic agents are important candidates in the development of maternal behaviours already during pregnancy.

Prolactin deficiency, obesity, and enlarged testes--a new syndrome?

Science.gov (United States)

Roitman, A; Assa, S; Kauli, R; Laron, Z

1980-01-01

A 4-year-old boy is described who was obese and slightly mentally retarded. His testes were enlarged. The only endocrine disorder present was a failure to increase plasma prolactin after stimulation. Images Figure PMID:7436524

Defective distal regulatory element at the 5' upstream of rat prolactin gene of steroid-nonresponsive GH-subclone.

Science.gov (United States)

Kumar, V; Wong, D T; Pasion, S G; Biswas, D K

1987-12-08

The prolactin-nonproducing (PRL-) GH cell strains (rat pituitary tumor cells in culture). GH12C1 and F1BGH12C1, do not respond to steroid hormones estradiol or hydrocortisone (HC). However, the stimulatory effect of estradiol and the inhibitory effect of hydrocortisone on prolactin synthesis can be demonstrated in the prolactin-producing GH cell strain, GH4C1. In this investigation we have examined the 5' end flanking region of rat prolactin (rat PRL) gene of steroid-responsive, GH4C1 cells to identify the positive and negative regulatory elements and to verify the status of these elements in steroid-nonresponsive F1BGH12C1 cells. Results presented in this report demonstrate that the basel level expression of the co-transferred Neo gene (neomycin phosphoribosyl transferase) is modulated by the distal upstream regulatory elements of rat PRL gene in response to steroid hormones. The expression of adjacent Neo gene is inhibited by dexamethasone and is stimulated by estradiol in transfectants carrying distal regulatory elements (SRE) of steroid-responsive cells. These responses are not observed in transfectants with the rat PRL upstream sequences derived from steroid-nonresponsive cells. The basal level expression of the host cell alpha-2 tubulin gene is not affected by dexamethasone. We report here the identification of the distal steroid regulatory element (SRE) located between 3.8 and 7.8 kb upstream of the transcription initiation site of rat PRL gene. Both the positive and the negative effects of steroid hormones can be identified within this upstream sequence. This distal SRE appears to be nonfunctional in steroid-nonresponsive cells. Though the proximal SRE is functional, the defect in the distal SRE makes the GH substrain nonresponsive to steroid hormones. These results suggest that both the proximal and the distal SREs are essential for the mediation of action of steroid hormones in GH cells.

Peripheral administration of palmitoylated prolactin-releasing peptide induces Fos expression in hypothalamic neurons involved in energy homeostasis in NMRI male mice

Czech Academy of Sciences Publication Activity Database

Pirník, Zdenko; Železná, Blanka; Kiss, A.; Maletínská, Lenka

2015-01-01

Roč. 1625, Nov 2 (2015), s. 151-158 ISSN 0006-8993 R&D Projects: GA ČR(CZ) GA15-08679S Institutional support: RVO:61388963 Keywords : hypothalamus * prolactin-releasing peptide * Fos * oxytocin * hypocretin * mice Subject RIV: CE - Biochemistry Impact factor: 2.561, year: 2015

Role of Mammary Prolactin in Carcinogenesis

Science.gov (United States)

1998-10-01

lactating rats (167) and dairy kines tested, IL-4 was the most potent inhibitor of myome- cows (174) by bromocriptine did not lower immunoreactive trial...of prolactin in dairy cows during lactogenesis. J Dairy 151. Chapitis J, Riddick DH, Betz LM, Brumsted JR, Gibson M, Prior Sci 70:2241-2253 JC, Gout...factors, insulin (30) and EGF (31) stim- ing the presence of functional postreceptor signaling mech- ulate, whereas transforming growth factor-P

Effects of cortisol, growth hormone and prolactin on gill claudin expression in Atlantic salmon

DEFF Research Database (Denmark)

Tipsmark, Christian Kølbæk; Jørgensen, Charlotte; Brande-Lavridsen, Nanna

2009-01-01

We recently showed that a series of tight junction proteins of the claudin family are regulated in the gill of salmon during salinity acclimation. The aim of the present study was to investigate the role of cortisol, growth hormone (GH) and prolactin (PRL) on regulation of expression of these iso......We recently showed that a series of tight junction proteins of the claudin family are regulated in the gill of salmon during salinity acclimation. The aim of the present study was to investigate the role of cortisol, growth hormone (GH) and prolactin (PRL) on regulation of expression...... antagonists RU486 and spironolactone, respectively. The observed in vitro responses were blocked by RU486, suggesting the involvement of a glucocorticoid type receptor. Injections of FW salmon with cortisol increased the expression of claudin 10e, 27a, and 30 but did not affect claudin 28a and 28b...... significantly. While GH had no effect on its own, the combination of GH and cortisol reduced claudin 28b levels. Injection of SW salmon with PRL selectively increased the expression of claudin 28a but had no effect on the other examined isoforms. The data shows that FW- (27a and 30) and SW-induced (10e...

Role of early growth response 1 in arteriogenesis: impact on vascular cell proliferation and leukocyte recruitment in vivo.

Science.gov (United States)

Pagel, Judith-Irina; Ziegelhoeffer, Tibor; Heil, Matthias; Fischer, Silvia; Fernández, Borja; Schaper, Wolfgang; Preissner, Klaus T; Deindl, Elisabeth

2012-03-01

Based on previous findings that early growth response 1 (Egr-1) participates in leukocyte recruitment and cell proliferation in vitro, this study was designed to investigate its mode of action during arteriogenesis in vivo. In a model of peripheral arteriogenesis, Egr-1 was significantly upregulated in growing collaterals of wild-type (WT) mice, both on mRNA and protein level. Egr-1(-/-) mice demonstrated delayed arteriogenesis after femoral artery ligation. They further showed increased levels of monocytes and granulocytes in the circulation, but reduced levels in adductor muscles under baseline conditions. After femoral artery ligation, elevated numbers of macrophages were detected in the perivascular zone of collaterals in Egr-1(-/-) mice and mRNA of leukocyte recruitment mediators was upregulated. Other Egr family members (Egr-2 to -4) were significantly upregulated only in Egr-1(-/-) mice, suggesting a mechanism of counterbalancing Egr-1 deficiency. Moreover, splicing factor-1, downregulated in WT mice after femoral artery ligation in the process of increased vascular cell proliferation, was upregulated in Egr-1(-/-) mice. αSM-actin on the other hand, significantly downregulated in WT mice, showed no differential expression in Egr-1(-/-) mice. While cell cycle regulator cyclin E and cdc20 were upregulated in Egr-1(-/-) mice, cyclin D1 expression decreased below the detection limit in collaterals, and the proliferation marker ki67 was not differentially expressed. In conclusion, compensation for deficiency in Egr-1 function in leukocyte recruitment can presumably be mediated by other transcription factors; however, Egr-1 is indispensable for effective vascular cell cycle progression in arteriogenesis.

Seasonal and biological variation of blood concentrations of total cholesterol, dehydroepiandrosterone sulfate, hemoglobin A(1c), IgA, prolactin, and free testosterone in healthy women

DEFF Research Database (Denmark)

Garde, A H; Hansen, Åse Marie; Skovgaard, L T

2000-01-01

Concentrations of physiological response variables fluctuate over time. The present study describes within-day and seasonal fluctuations for total cholesterol, dehydroepiandrosterone sulfate (DHEA-S), hemoglobin A(1c) (HbA(1c)), IgA, prolactin, and free testosterone in blood, and estimates within......- (CV(i)) and between-subject (CV(g)) CVs for healthy women. In addition, the index of individuality, prediction intervals, and power calculations were derived....

Prolactin, cortisol and thyroxine levels and the premature infant

African Journals Online (AJOL)

1983-04-16

Apr 16, 1983 ... and the premature infant ... values in cord and maternal plasma to fetal age and weight and to the incidence of hyaline membrane disease (HMD) was .... thyroxine and prolactin values with an increase in weight has also.

Evaluation of the human prolactin of National Production for use in radioimmunoassay (RIA); Evaluacion de la prolactina humana de produccion nacional para su empleo en radioimmunoanalisis (RIA)

Energy Technology Data Exchange (ETDEWEB)

Caso, R [Centro de Isotopos, La Habana (Cuba); Arranz, C [Instituto Nacional de Endocrinologia, La Habana (Cuba)

1996-07-01

In this work was studied the possibility of using the Prolactin hormone as raw material to produce Kits-RIA of Prolactin. Was used the prolactin, which is obtained in Cuba by the Pharmaceutical Institute Mario Munoz. Was made the labbeling of Prolactin with I-125, was used the hormone as standard and were done the probes of quality control. The Prolactin Hormone had the necesary quality to produce Kits-RIA-Prolactin.

Comparison of EGR-VTG control schemes for an EPA2010 heavy-duty diesel engine

NARCIS (Netherlands)

Criens, C.H.A.; Willems, F.P.T.; Steinbuch, M.

2011-01-01

Next generation heavy-duty diesel engines require tight air path control to meet upcoming emission legislation with minimal fuel consumption. This study concentrates on the emission control of a 13l, 360 kW EGR diesel engine, which is compliant with EPA2010 emission targets. Currently, an

The involvement of prolactin in avian molt: the effects of gender and breeding success on the timing of molt in Mute swans (Cygnus olor).

Science.gov (United States)

Dawson, A; Perrins, C M; Sharp, P J; Wheeler, D; Groves, S

2009-04-01

The aim of the study was to test the hypothesis that decreasing plasma prolactin stimulates or permits the initiation of avian molt. Changes in the concentration of plasma prolactin in Mute swans (Cygnus olor) were compared in non-breeding singletons and breeding pairs. In breeding swans, the onset of molt is delayed compared to non-breeders, and is delayed further in breeding males compared to their female partners. The seasonal decrease in prolactin in non-breeding birds of both sexes started at the end of May and was associated with the initiation of molt 4 weeks later. The decrease in plasma prolactin in incubating females was more pronounced, as a consequence of increased prolactin secretion associated with incubation behavior, but also started at end of May, and was associated the onset of molt 6 weeks later. In breeding males, plasma prolactin increased at the end of May when they started to care for their newly hatched cygnets. Correspondingly, prolactin began to decrease 3-5 weeks later in males than in females. These males started to molt in mid August, at least 4 weeks later than females. It is concluded that molt is related to decreasing plasma prolactin, and is inhibited when plasma prolactin is increasing or high.

Influence of Regularity of Exposure to Chronic Stress on the Pattern of Habituation of Pituitary-Adrenal Hormones, Prolactin and Glucose.

Science.gov (United States)

Martí; Armario

1997-05-01

The effect of regularity of exposure to two different chronic stressors (noise or immobilization (IMO)) on the pattern of habituation of pituitary-adrenal (PA) hormones, prolactin and glucose was evaluated in adult male rats. Animals were chronically subjected to either regular or irregular time schedule of noise (30 min/day) or IMO (2 h/day) for two weeks. The day after the last stress session the rats were killed without stress or after having been subjected to 30 min of the homotypic stressor. Whereas regular noise did not affect food intake, body weight gain or adrenal weight, irregular noise decreased body weight gain and induced a moderate adrenal hypertrophy. In addition, previous daily exposure to regular but not to irregular noise reduced both prolactin and corticosterone responses to acute noise. In contrast, glucose response to acute noise was reduced after both regular and irregular exposure to chronic noise. Either regular or irregular exposure to chronic IMO decreased food intake and body weight and increased adrenal weight to the same extent. Likewise, no influence of regularity of exposure to chronic IMO on corticosterone and prolactin responses to acute IMO was observed. However, habituation of the ACTH response to acute IMO was observed in rats subjected to chronic regular IMO, but not in rats subjected to chronic irregular IMO. Finally, acute IMO-induced hyperglycemia diminished to the same extent after regular and irregular IMO. From these results we can conclude that: first, the process of habituation of the PA axis to chronic stress is greatly dependent upon factors such as regularity of exposure to the stressor and stressor intensity, and second, the influence of regularity on the pattern of habituation to a repeated stressor is dependent on the physiological variable we are dealing with.