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Sample records for 1b prolactin receptor

  1. The 5-HT1D/1B receptor agonist sumatriptan enhances fear of simulated speaking and reduces plasma levels of prolactin.

    Science.gov (United States)

    de Rezende, Marcos Gonçalves; Garcia-Leal, Cybele; Graeff, Frederico Guilherme; Del-Ben, Cristina Marta

    2013-12-01

    This study measured the effects of the preferential 5-HT1D/1B receptor agonist sumatriptan in healthy volunteers who performed the Simulated Public Speaking Test (SPST), which recruits the neural network involved in panic disorder and social anxiety disorder. In a double-blind, randomised experiment, 36 males received placebo (12), 50 mg (12) or 100 mg (12) of sumatriptan 2 h before the SPST. Subjective, physiological and hormonal measures were taken before, during and after the test. The dose of 100 mg of sumatriptan increased speech-induced fear more than either a 50mg dose of the drug or placebo. The largest dose of sumatriptan also enhanced vigilance more than placebo, without any change in blood pressure, heart rate or electrical skin conductance. Sumatriptan decreased plasma levels of prolactin. A significant but moderate increase in plasma cortisol after SPST occurred, independent of treatment. Because sumatriptan decreases 5-HT release into the extracellular space, the potentiation of SPST-induced fear caused by the drug supports the hypothesis that 5-HT attenuates this emotional state. As acute administration of antidepressants has also been shown to enhance speaking fear and increase plasma prolactin, in contrast to sumatriptan, the 5-HT regulation of stress-hormone release is likely to be different from that of emotion.

  2. Prolactin transport into mouse brain is independent of prolactin receptor.

    Science.gov (United States)

    Brown, Rosemary S E; Wyatt, Amanda K; Herbison, Ryan E; Knowles, Penelope J; Ladyman, Sharon R; Binart, Nadine; Banks, William A; Grattan, David R

    2016-02-01

    The anterior pituitary hormone prolactin exerts important physiologic actions in the brain. However, the mechanism by which prolactin crosses the blood-brain barrier and enters the brain is not completely understood. On the basis of high expression of the prolactin receptor in the choroid plexus, it has been hypothesized that the receptor may bind to prolactin in the blood and translocate it into the cerebrospinal fluid (CSF). This study aimed to test this hypothesis by investigating transport of (125)I-labeled prolactin ((125)I-prolactin) into the brain of female mice in the presence and absence of the prolactin receptor (PRLR(-/-)). Peripherally administered prolactin rapidly activates brain neurons, as evidenced by prolactin-induced phosphorylation of signal transducer and activator of transcription 5 (pSTAT5) in neurons within 30 min of administration. The transport of prolactin into the brain was saturable, with transport effectively blocked only by a very high dose of unlabeled ovine prolactin. Transport was regulated, as in lactating mice with chronically elevated levels of prolactin, the rate of (125)I-prolactin transport into the brain was significantly increased compared to nonlactating controls. There was no change in the rate of (125)I-prolactin transport into the brain in PRLR(-/-) mice lacking functional prolactin receptors compared to control mice, indicating transport is independent of the prolactin receptor. These data suggest that prolactin transport into the brain involves another as yet unidentified transporter molecule. Because CSF levels of (125)I-prolactin were very low, even up to 90 min after administration, the data suggest that CSF is not the major route by which blood prolactin gains access to neurons in the brain.

  3. Prolactin-like activity of anti-prolactin receptor antibodies on casein and DNA synthesis in the mammary gland.

    OpenAIRE

    Djiane, J; Houdebine, L M; Kelly, P A

    1981-01-01

    Prolactin receptors were partially purified from rabbit mammary gland membranes by using an affinity chromatography technique. Antibodies against this prolactin receptor preparation were obtained in guinea pig and sheep. Both antisera were able to inhibit the binding of 125I-labeled ovine prolactin to rabbit mammary gland membranes. When added to culture media of rabbit mammary explants, the anti-prolactin receptor antiserum inhibited the capacity of prolactin to initiate casein synthesis and...

  4. Role of Prolactin Receptors in Lymphangioleiomyomatosis.

    Directory of Open Access Journals (Sweden)

    Amira Alkharusi

    Full Text Available Pulmonary lymphangioleiomyomatosis (LAM is a rare lung disease caused by mutations in the tumor suppressor genes encoding Tuberous Sclerosis Complex (TSC 1 and TSC2. The protein product of the TSC2 gene is a well-known suppressor of the mTOR pathway. Emerging evidence suggests that the pituitary hormone prolactin (Prl has both endocrine and paracrine modes of action. Here, we have investigated components of the Prl system in models for LAM. In a TSC2 (+/- mouse sarcoma cell line, down-regulation of TSC2 using siRNA resulted in increased levels of the Prl receptor. In human LAM cells, the Prl receptor is detectable by immunohistochemistry, and the expression of Prl in these cells stimulates STAT3 and Erk phosphorylation, as well as proliferation. A high affinity Prl receptor antagonist consisting of Prl with four amino acid substitutions reduced phosphorylation of STAT3 and Erk. Antagonist treatment further reduced the proliferative and invasive properties of LAM cells. In histological sections from LAM patients, Prl receptor immuno reactivity was observed. We conclude that the Prl receptor is expressed in LAM, and that loss of TSC2 increases Prl receptor levels. It is proposed that Prl exerts growth-stimulatory effects on LAM cells, and that antagonizing the Prl receptor can block such effects.

  5. Tissue-specific Regulation of Porcine Prolactin Receptor Expression by Estrogen, Progesterone and Prolactin

    Science.gov (United States)

    Prolactin (PRL) acts through its receptor (PRLR) via both endocrine and local paracrine/autocrine pathways to regulate biological processes including reproduction and lactation. We analyzed the tissue and stage of gestation-specific regulation of PRL and PRLR expression in various tissues of pigs. ...

  6. Prolactin and prolactin receptor expression in cervical intraepithelial neoplasia and cancer.

    Science.gov (United States)

    Ascencio-Cedillo, Rafael; López-Pulido, Edgar Ivan; Muñoz-Valle, José Francisco; Villegas-Sepúlveda, Nicolás; Del Toro-Arreola, Susana; Estrada-Chávez, Ciro; Daneri-Navarro, Adrian; Franco-Topete, Ramón; Pérez-Montiel, Delia; García-Carrancá, Alejandro; Pereira-Suárez, Ana Laura

    2015-04-01

    Prolactin receptor (PRLR) overexpression could play a role in tumorigenesis. The aim of this study was to determine prolactin (PRL) and PRLR expression in biopsies from patients with precursor lesions and uterine cervical cancer. PRLR expression was analyzed in 63 paraffin-embedded biopsies of uterine cervical tissue. In total, eleven low-grade squamous intraepithelial lesions (LSIL), 23 high-grade squamous intraepithelial lesions (HSIL), 21 uterine cervical cancers (UCC) and 8 normal epithelium (NE) were examined using immunoperoxidase staining and Western blot analysis. Additionally, PRL expression was identified in human cervical cancer serum and tissues. The PRLR expression was found to be significantly increased in cervical cancer in comparison with normal tissue and precursor lesions (P prolactin expression was similar in precursor lesions and cervical cancer by Western blot analysis. Our data suggest a possible role for PRLR in the progression of cervical cancer.

  7. Prolactin (PRL) and prolactin receptor (PRLR) genes and their role in poultry production traits.

    Science.gov (United States)

    Wilkanowska, Anna; Mazurowski, Artur; Mroczkowski, Sławomir; Kokoszyński, Dariusz

    2014-01-01

    Prolactin (PRL), secreted from the anterior pituitary, plays extensive roles in osmoregulation, corpus luteum formation, mammogenesis, lactogenesis, lactopoiesis, and production of crop milk. In birds, prolactin (PRL) is generally accepted as crucial to the onset and maintenance of broodiness. All the actions of prolactin (PRL) hormone are mediated by its receptor (PRLR), which plays an important role in the PRL signal transduction cascade. It has been well established that the PRL gene is closely associated to the onset and maintenance of broody behavior, and could be a genetic marker in breeding against broodiness in chickens. Meanwhile, the prolactin receptor (PRLR) gene is regarded as a candidate genetic marker for reproductive traits. PRLR is also an important regulator gene for cell growth and differentiation. The identified polymorphism of this gene is mainly viewed in terms of egg production traits. Due to different biological activities attributed to PRL and PRLR, they can be used as major candidate genes in molecular animal breeding programs. Characterization of PRL and PRLR genes helps to elucidate their roles in birds and provides insights into the regulatory mechanisms of PRL and PRLR expression conserved in birds and mammals.

  8. Comparative genomics reveals tissue-specific regulation of prolactin receptor gene expression

    Science.gov (United States)

    Prolactin (PRL), acting via the prolactin receptor, fulfills a diversity of biological functions including the maintenance of solute balance and mineral homeostasis via tissues such as the heart, kidneys and intestine. Expression and activity of the prolactin receptor (PRLR) is regulated by various ...

  9. Structure-Function Studies on the Prolactin Receptor

    DEFF Research Database (Denmark)

    Haxholm, Gitte Wolfsberg

    Class 1 Cytokine receptors are involved in important biological functions mediated through complex networks of intracellular signaling. However, the molecular details of how signaling is regulated are poorly understood. One of the primary reasons for this limited knowledge is the lack of structural...... information on the intracellular domains (ICDs) of these receptors. The overall aim of this study was to obtain an improved understanding of cytokine receptor signaling through structure-function studies on the prolactin receptor (PRLR). The primary focus of this thesis was to structurally characterize...... the PRLR-ICD and the ICD of the related growth hormone receptor (GHR). We showed that both ICDs were intrinsically disordered throughout their entire lengths and that they associated with lipids characteristic of the inner plasma membrane leaflet through conserved motifs, implicating the membrane...

  10. Effects of metoclopramide-induced hyperprolactinemia on the prolactin and prolactin receptor expression of murine adrenal.

    Science.gov (United States)

    do Amaral, Vinícius Cestari; da Silva, Priscilla Ludovico; Carvalho, Kátia Candido; Simoncini, Tommaso; Maciel, Gustavo Arantes Rosa; Soares-Jr, José Maria; Baracat, Edmund Chada

    2015-01-01

    The aim of this study was to evaluate the effects of metoclopramide-induced hyperprolactinemia on the prolactin (PRL) and prolactin receptor's (PRLR) expression in the adrenal. For this purpose, a total of 12 animals with intact ovaries were allocated to two groups: G1 (saline solution) and G2 (metoclopramide). A total of 30 oophorectomized animals was randomized to five subgroups: G3 (saline solution), G4 (metoclopramide), G5 (metoclopramide + 17β-estradiol), G6 (metoclopramide + progesterone), and G7 (metoclopramide + 17β-estradiol + progesterone). Immunohistochemical analyses were evaluated semi-quantitatively. For PRLR, the area fraction of labeled cells (ALC) varied from 1 (0-10%) to 3 (> 50%). Based on the mean of the immunostaining intensity, G2 and G4 showed strong expression; G6 and G7 presented a mild reaction; and G1, G3, and G5 exhibited a weak reaction. Concerning PRL, the ALC varied from 1 (0-10%) to 3 (> 50%), and groups G6 and G7 showed a strong reaction; G2, G4, and G5 showed a mild reaction; and G1 and G3 exhibited a weak reaction. These findings suggest that metoclopramide-induced hyperprolactinemia increases PRL expression in the adrenal glands of mice. Furthermore, progesterone alone or in association with estrogen also increases PRL expression, but to a lesser extent.

  11. The progesterone and estrogen modify the uterine prolactin and prolactin receptor expression of hyperprolactinemic mice.

    Science.gov (United States)

    do Amaral, Vinícius Cestari; Carvalho, Kátia Candido; Maciel, Gustavo Arantes Rosa; Simoncini, Tommaso; da Silva, Priscilla Ludovico; Marcondes, Rodrigo Rodrigues; Soares, José Maria; Baracat, Edmund Chada

    2015-02-01

    The aim of this study was to evaluate the effects of metoclopramide-induced hyperprolactinemia on the prolactin (PRL) and PRL receptor's expression in the uterus of mice. For this purpose, 49 Swiss mice were divided into the following groups: GrSS (non-ovariectomized mice given vehicle); GrMET (non-ovariectomized mice treated with metoclopramide); OvSS (ovariectomized mice given vehicle); OvMET (ovariectomized mice treated with metoclopramide); OvMET+17βE (ovariectomized mice treated with metoclopramide and 17β estradiol); OvMET+MP (ovariectomized mice treated with metoclopramide and micronized progesterone); OvMET+17βE+MP (ovariectomized mice treated with metoclopramide and a solution of 17β estradiol and micronized progesterone). Immunohistochemical analyzes were evaluated semi-quantitatively. Our results showed that GrMET, OvMET+MP, and OvMET+17βE+MP presented strong PRL expression. OvMET and OvMET+17βE presented mild reaction, while GrSS and OvSS presented weak reaction. Concerning PRL receptor, OvMET+MP and OvMET+17βE+MP showed strong reaction; GrMET, OvSS, and OvMET+17βE showed mild reaction; and GrSS and OvMET showed weak reaction. These findings suggest that progesterone alone or in combination with estrogen may increase the expression of uterine PRL and PRL receptor.

  12. [Action mechanisms of prolactin and its receptors on penile erection and ejaculation].

    Science.gov (United States)

    Zhang, Jian-zhong; Xu, Ai-ming; Chen, Wei; Wang, Zeng-jun

    2015-12-01

    Prolactin is a polypeptide hormone which mainly acts on the reproductive system and plays an important role in penile erection and ejaculation. Prolactin receptors have a variety of short forms apart from the classic long form, which are widely expressed in male reproductive glands. High levels of prolactin can induce erectile dysfunction and results in secondary male infertility, which are mainly associated with the inhibition of dopaminergic activity, reduction of the testosterone level, and contraction of the cavernous smooth muscle. Moreover, low levels of prolactin can result in ejaculatory dysfunction. This article updates the views on the expressions of prolactin receptors in the male reproductive system, the effects of prolactin on penile erection and ejaculation, and its action mechanisms.

  13. Prolactin receptor and signal transduction to milk protein genes

    Energy Technology Data Exchange (ETDEWEB)

    Djiane, J.; Daniel, N.; Bignon, C. [Unite d`Endocrinologie Moleculaire, Jouy en Josas (France)] [and others

    1994-06-01

    After cloning of the mammary gland prolactin (PRL) receptor cDNA, a functional assay was established using co-transfection of PRL receptor cDNA together with a milk protein promoter/chloramphenicol acetyl transferase (CAT) construct in Chinese hamster ovary (CHO) cells. Different mutants of the PRL receptor were tested in this CAT assay to delimit the domains in the receptor necessary for signal transduction to milk protein genes. In CHO cells stably transfected with PRL receptor cDNA, high numbers of PRL receptor are expressed. By metabolic labeling and immunoprecipitation, expressed PRL receptor was identified as a single species of 100 kDa. Using these cells, we analyzed the effects of PRL on intracellular free Ca{sup ++} concentration. PRL stimulates Ca{sup ++} entry and induces secondary Ca{sup ++} mobilization. The entry of Ca{sup ++} is a result of an increase in K{sup +} conductance that hyperpolarizes the membranes. We have also analyzed tyrosine phosphorylation induced by PRL. In CHO cells stably transfected with PRL receptor cDNA, PRL induced a very rapid and transient tyrosine phosphorylation of a 100-kDa protein which is most probably the PRL receptor. The same finding was obtained in mammary membranes after PRL injection to lactating rabbits. Whereas tyrosine kinase inhibitors genistein and lavendustin were without effect, PRL stimulation of milk protein gene promoters was partially inhibited by 2 {mu}M herbimycin in CHO cells co-transfected with PRL receptor cDNA and the {Beta} lactoglobulin CAT construct. Taken together these observations indicate that the cytoplasmic domain of the PRL receptor interacts with one or several tyrosine kinases, which may represent early postreceptor events necessary for PRL signal transduction to milk protein genes. 14 refs., 4 figs.

  14. Characterization of ductal and lobular breast carcinomas using novel prolactin receptor isoform specific antibodies

    Directory of Open Access Journals (Sweden)

    Heger Christopher D

    2010-12-01

    Full Text Available Abstract Background Prolactin is a polypeptide hormone responsible for proliferation and differentiation of the mammary gland. More recently, prolactin's role in mammary carcinogenesis has been studied with greater interest. Studies from our laboratory and from others have demonstrated that three specific isoforms of the prolactin receptor (PRLR are expressed in both normal and cancerous breast cells and tissues. Until now, reliable isoform specific antibodies have been lacking. We have prepared and characterized polyclonal antibodies against each of the human PRLR isoforms that can effectively be used to characterize human breast cancers. Methods Rabbits were immunized with synthetic peptides of isoform unique regions and immune sera affinity purified prior to validation by Western blot and immunohistochemical analyses. Sections of ductal and lobular carcinomas were stained with each affinity purified isoform specific antibody to determine expression patterns in breast cancer subclasses. Results We show that the rabbit antibodies have high titer and could specifically recognize each isoform of PRLR. Differences in PRLR isoform expression levels were observed and quantified using histosections from xenografts of established human breast cancer cells lines, and ductal and lobular carcinoma human biopsy specimens. In addition, these results were verified by real-time PCR with isoform specific primers. While nearly all tumors contained LF and SF1b, the majority (76% of ductal carcinoma biopsies expressed SF1a while the majority of lobular carcinomas lacked SF1a staining (72% and 27% had only low levels of expression. Conclusions Differences in the receptor isoform expression profiles may be critical to understanding the role of PRL in mammary tumorigenesis. Since these antibodies are specifically directed against each PRLR isoform, they are valuable tools for the evaluation of breast cancer PRLR content and have potential clinical importance in

  15. Development of prolactin receptor antagonists with reduced pH-dependence of receptor binding

    DEFF Research Database (Denmark)

    Hansen, Mathilde Johanne Kaas; Olsen, Johan Gotthardt; Bernichtein, Sophie;

    2011-01-01

    H than at physiological pH and since the extracellular environment around solid tumors often is acidic, it is desirable to develop antagonists that have improved binding affinity at low pH. The pK(a) value of a histidine side chain is ~6.8 making histidine residues obvious candidates for examination....... From evaluation of known molecular structures of human prolactin, of the prolactin receptor and of different complexes of the two, three histidine residues in the hormone-receptor binding site 1 were selected for mutational studies. We analyzed 10 variants by circular dichroism spectroscopy, affinity...... and thermodynamic characterization of receptor binding by isothermal titration calorimetry combined with in vitro bioactivity in living cells. Histidine residue 27 was recognized as a central hot spot for pH sensitivity and conservative substitutions at this site resulted in strong receptor binding at low pH. Pure...

  16. Expression of prolactin receptor and response to prolactin stimulation of human NK cell lines

    Institute of Scientific and Technical Information of China (English)

    Rui SUN; Ai Ling LI; Hai Ming WEI; Zhi Gang TIAN

    2004-01-01

    We have previously shown a critical role of prolactin (PRL) during maturation and anti-tumor effects of murine natural killer (NK) cells in vitro and in vivo. We extended that study by exploring the ability of human NK cell lines (NK-92 and YT cell) to express PRL receptor (PRL-R) and to respond to PRL stimulation in vitro. Both human NK cell lines constitutively expressed PRL-R on membrane and mRNA transcripts,NK-92 cells contained higher level of PRL-R than YT cells,which correlated to the enhanced capacity of the cells to proliferate and to lyse target cells in response to PRL stimulation in the presence of trace amount of IL-2 or IL-15 in vitro. Two differences between IL-2 and IL-15 in functioning on human NK cells were for the first time observed. PRL synergized with IL-15 to improve proliferation of NK cells in a dose-dependent manner without double peak manifesting like IL-2. Although PRL enhanced the cytotoxicity of IL-2 or IL- 15 activated NK cells,it exerted the function through up-regulating gene expression of perforin without influence of FasL in IL-2-stimulated NK cells,while in IL-15-stimulated NK cells,PRL did the function through up-regulating gene expression of both perforin and FasL but not IFNγ. PRL increased expressions of IL-2Rα on membrane and of IL-2 mRNA in cells,indicating that PRL up-regulated NK cell function by improving positive feedback between IL-2 and IL-2R. The similar results were also observed in network between IL-15 and IL-15R. These data indicate a potential role of PRL in human NK cell modulation.

  17. Associations of the 5-hydroxytryptamine (Serotonin) Receptor 1B Gene (HTR1B) with Alcohol, Cocaine, and Heroin Abuse

    OpenAIRE

    Cao, Jian; LaRocque, Emily; Li, Dawei

    2013-01-01

    Abnormal serotonergic pathways are implicated in numerous neuropsychiatric disorders including alcohol and drug dependence (abuse). The human 5-hydroxytryptamine (serotonin) receptor 1B, encoded by the HTR1B (5-HT1B) gene, is a presynaptic serotonin autoreceptor that plays an important role in regulating serotonin synthesis and release. Although there was evidence of associations of the HTR1B gene variants in the etiologies of substance use disorders, negative findings were also reported. To ...

  18. An estrogen receptor model to describe the regulation of prolactin synthesis by antiestrogens in vitro.

    Science.gov (United States)

    Lieberman, M E; Gorski, J; Jordan, V C

    1983-04-25

    A hypothetical model of the ligand interaction with the estrogen receptor binding site has been developed to describe the structural features necessary to initiate or to inhibit prolactin synthesis in vitro. The biological potency of the binding ligands is directly related to their relative binding affinity (RBA) for the estrogen receptor. The relative potencies of antiestrogens to inhibit estradiol-stimulated prolactin synthesis was trans-monohydroxytamoxifen identical to cis-monohydroxytamoxifen identical to tamoxifen, consistent with their RBAs for uterine estrogen receptor. Similarly the relative potency of estrogens to stimulate prolactin synthesis was diethylstilbestrol identical to estradiol greater than ICI 77,949 greater than ICI 47,699 identical to zuclomiphene, consistent with their RBAs. The compound LY126412 (trioxifene without the aminoethoxy side chain) did not interact with the estrogen receptor at the concentrations tested (10(-8)--10(-6) M) or exhibit estrogenic or antiestrogenic properties using the prolactin synthesis assay. Overall, the ligand-receptor model stresses the structural requirement for high affinity binding and the critical positioning of the alkylamino-ethoxy side chain in space (in relation to the ligand-binding site on the estrogen receptor) to prevent prolactin synthesis.

  19. A combined computational and structural model of the full-length human prolactin receptor

    Science.gov (United States)

    Bugge, Katrine; Papaleo, Elena; Haxholm, Gitte W.; Hopper, Jonathan T. S.; Robinson, Carol V.; Olsen, Johan G.; Lindorff-Larsen, Kresten; Kragelund, Birthe B.

    2016-05-01

    The prolactin receptor is an archetype member of the class I cytokine receptor family, comprising receptors with fundamental functions in biology as well as key drug targets. Structurally, each of these receptors represent an intriguing diversity, providing an exceptionally challenging target for structural biology. Here, we access the molecular architecture of the monomeric human prolactin receptor by combining experimental and computational efforts. We solve the NMR structure of its transmembrane domain in micelles and collect structural data on overlapping fragments of the receptor with small-angle X-ray scattering, native mass spectrometry and NMR spectroscopy. Along with previously published data, these are integrated by molecular modelling to generate a full receptor structure. The result provides the first full view of a class I cytokine receptor, exemplifying the architecture of more than 40 different receptor chains, and reveals that the extracellular domain is merely the tip of a molecular iceberg.

  20. A combined computational and structural model of the full-length human prolactin receptor

    DEFF Research Database (Denmark)

    Bugge, Katrine Østergaard; Papaleo, Elena; Haxholm, Gitte Wolfsberg

    2016-01-01

    for structural biology. Here, we access the molecular architecture of the monomeric human prolactin receptor by combining experimental and computational efforts. We solve the NMR structure of its transmembrane domain in micelles and collect structural data on overlapping fragments of the receptor with small...

  1. A combined computational and structural model of the full-length human prolactin receptor

    DEFF Research Database (Denmark)

    Bugge, Katrine Østergaard; Papaleo, Elena; Haxholm, Gitte Wolfsberg;

    2016-01-01

    The prolactin receptor is an archetype member of the class I cytokine receptor family, comprising receptors with fundamental functions in biology as well as key drug targets. Structurally, each of these receptors represent an intriguing diversity, providing an exceptionally challenging target...... for structural biology. Here, we access the molecular architecture of the monomeric human prolactin receptor by combining experimental and computational efforts. We solve the NMR structure of its transmembrane domain in micelles and collect structural data on overlapping fragments of the receptor with small......-angle X-ray scattering, native mass spectrometry and NMR spectroscopy. Along with previously published data, these are integrated by molecular modelling to generate a full receptor structure. The result provides the first full view of a class I cytokine receptor, exemplifying the architecture of more than...

  2. Prolactin and dopamine 1-like receptor interaction in renal proximal tubular cells.

    Science.gov (United States)

    Crambert, Susanne; Sjöberg, Agneta; Eklöf, Ann-Christine; Ibarra, Fernando; Holtbäck, Ulla

    2010-07-01

    Prolactin is a natriuretic hormone and acts by inhibiting the activity of renal tubular Na(+)-K(+)-ATPase activity. These effects require an intact renal dopamine system. Here, we have studied by which mechanism prolactin and dopamine interact in Sprague-Dawley rat renal tissue. Na(+)-K(+)-ATPase activity was measured as ouabain-sensitive ATP hydrolysis in microdissected renal proximal tubular segments. Intracellular signaling pathways were studied by a variety of different techniques, including Western blotting using phosphospecific antibodies, immunoprecipitation, and biotinylation assays. We found that dopamine and prolactin regulated Na(+)-K(+)-ATPase activity via similar signaling pathways, including protein kinase A, protein kinase C, and phosphoinositide 3-kinase activation. The cross talk between prolactin and dopamine 1-like receptors was explained by a heterologous recruitment of dopamine 1-like receptors to the plasma membrane in renal proximal tubular cells. Prolactin had no effect on Na(+)-K(+)-ATPase activity in spontaneously hypertensive rats, a rat strain with a blunted response to dopamine. These results further emphasize the central role of the renal dopamine system in the interactive regulation of renal tubular salt balance.

  3. Prolactin receptor and osteogenic induction of prolactin in human periodontal ligament fibroblasts.

    Science.gov (United States)

    Surarit, Rudee; Krishnamra, Nateetip; Seriwatanachai, Dutmanee

    2016-04-01

    Prolactin is an important hormone involved in the interaction between maternal, extraembryonic, and fetal tissues that remains in high levels during the entire duration of pregnancy. Although many systemic alterations occur during pregnancy, such as hormonal changes, that are known to be associated with periodontitis and tooth loss, PRL function in human periodontal ligament fibroblasts (HPDLF) had never been studied. Herein, we investigated the role of PRL in the regulation of HPDLF proliferation and differentiation. HPDLF were cultured in differentiating medium with various concentrations of PRL. The present study demonstrated that HPDLF and primary human PDL cells that were extracted for orthodontic purpose expressed both short and long isoforms of PRLR mRNA and its proteins. An incubation with of high concentration of PRL (600 and 1,000 ng/mL) modestly decreased the HPDLF number. In contrast, PRL at a non-reproductive level (10 ng/mL) and pregnant level (100 ng/mL) significantly upregulated the markers of osteogenesis, such as RUNX2, BMP2, and POSTN, but not SOX9. Mineral nodule formation was induced, whereas proteoglycan accumulation was reduced by PRL suggesting that HPDLF were undergoing differentiation into preosteoblastic cells. In conclusion, the presence of hPRLR in human PDL together with PRL-induced upregulation of osteogenic markers strongly suggested a direct regulatory role of PRL in PDL and periodontal tissue development.

  4. Expression of prolactin receptors in normal canine mammary tissue, canine mammary adenomas and mammary adenocarcinomas

    Directory of Open Access Journals (Sweden)

    Michel Erika

    2012-05-01

    Full Text Available Abstract Background Mammary tumors represent the most common neoplastic disease in female dogs. Recently, the promoting role of prolactin (PRL in the development of human breast carcinoma has been shown. Possible proliferative, anti-apoptotic, migratory and angiogenic effects of PRL on human mammary cancer cells in vitro and in vivo were suggested. The effects of PRL are mediated by its receptor, and alterations in receptor expression are likely to play a role in tumor development. Currently, not much data is available about prolactin receptor (PRLR expression in canine mammary tumors. To set the basis for investigations on the role of PRL in mammary tumorigenesis in this species, prolactin receptor expression was evaluated by semi-quantitative real time PCR and immunohistochemistry on 10 formalin-fixed, paraffin-embedded samples each of canine non-neoplastic mammary tissue, mammary adenomas and adenocarcinomas. Results The highest PRLR expression levels were found in normal mammary tissue, while adenomas, and to an even higher degree adenocarcinomas, showed a significant decrease in prolactin receptor expression. Compared to normal tissue, PRLR mRNA was reduced 2.4 fold (p = 0.0261 in adenomas and 4.8 fold (p = 0.008 in adenocarcinomas. PRLR mRNA expression was significantly lower in malignant than in benign lesions (p = 0.0165. Immunohistochemistry demonstrated PRLR expression in all three tissue types with signals mostly limited to epithelial cells. Conclusions Malignant transformation of mammary tissue was associated with a decline in prolactin receptor expression. Further studies are warranted to address the functional significance of this finding.

  5. A novel first exon directs hormone-sensitive transcription of the pig prolactin receptor

    Science.gov (United States)

    Endocrine, paracrine, and autocrine prolactin (PRL) acts through its receptor (PRLR) to confer a wide range of biological functions, including its established role during lactation.We have identified a novel first exon of the porcine PRLR that gives rise to three different mRNA transcripts. Transcri...

  6. 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 to i...

  7. The in vitro effect of prolactin on the growth, motility and expression of prolactin receptors in larvae of Toxocara canis.

    Science.gov (United States)

    Chávez-Güitrón, L E; Morales-Montor, J; Muñoz-Guzmán, M A; Nava-Castro, K E; Ramírez-Álvarez, H; Moreno-Méndoza, N A; Hernández-Cervantes, R; Alba-Hurtado, F

    2016-07-15

    The in vitro effect of prolactin (PRL) on the growth and motility of Toxocara canis larvae was assessed. Additionally, the expression and location of prolactin receptors (PRL-Rs) were determined in the larvae. Larvae of T. canis were incubated with different concentrations of PRL for different periods of time. The stimulated larvae accelerated their enlargement and increased their motility. The mean percentage of PRL-R+ cells in non-stimulated larvae, measured by flow cytometry was 7.3±0.3%. Compared with non-stimulated larvae, the mean fluorescence intensity (p<0.05) increased in larvae incubated with 40ng/mL of PRL for 10 days. A 465-bp length fragment was amplified from larvae gDNA by PCR. The sequence of this fragment showed 99% similarity with the gene fragment that codes for the PRL-R of the domestic dog. A high concentration of PRL-Rs was immune-located in the posterior region of the larval intestine; therefore, the intestinal cells in this region were most likely the targets for this hormone. Based on these results, PRL-Rs were identified in T. canis larvae, and the in vitro stimulation with PRL increased the number of these receptors, accelerated the growth and modified the activity of larvae. All of the above suggest that T. canis larvae are evolutionarily adapted to recognize the PRL of their definitive host and furthermore might explain the reactivation of tissue-arrested larvae during the gestation of bitches, which does not occur in gestating females of other species.

  8. Ethanol and Mesolimbic Serotonin/Dopamine Interactions via 5HT-1B Receptors

    Science.gov (United States)

    2007-03-01

    Addiction, 101 (Suppl. 1): 23-30, 2006. 16. Kranzler HR, Hernandez -Avila CA, Gelenter J,: Polymorphism of the 5-HT1B receptor gene (HTR1B): strong within...Serotonin1B receptor stimulation enhances cocaine reinforcement, J. Neurosci., 18: 10078-10089, 1998. 25. Rojas -Corrales MO, Berrocoso E, Mico JA,: Role of...it has been reported that the effective receptor antagonist concentration of SB 216641 is similar to that of WAY 100635 ( Rojas -Corrales et al

  9. Predictions of in vivo prolactin levels from in vitro k I values of d 2 receptor antagonists using an agonist-antagonist interaction model

    NARCIS (Netherlands)

    Petersson, K.J.; Vermeulen, A.M.J.; Friberg, L.E.

    2013-01-01

    Prolactin elevation is a side effect of all currently available D2 receptor antagonists used in the treatment of schizophrenia. Prolactin elevation is the result of a direct antagonistic D2 effect blocking the tonic inhibition of prolactin release by dopamine. The aims of this work were to assess th

  10. A Novel Nectin-mediated Cell Adhesion Apparatus That Is Implicated in Prolactin Receptor Signaling for Mammary Gland Development.

    Science.gov (United States)

    Kitayama, Midori; Mizutani, Kiyohito; Maruoka, Masahiro; Mandai, Kenji; Sakakibara, Shotaro; Ueda, Yuki; Komori, Takahide; Shimono, Yohei; Takai, Yoshimi

    2016-03-11

    Mammary gland development is induced by the actions of various hormones to form a structure consisting of collecting ducts and milk-secreting alveoli, which comprise two types of epithelial cells known as luminal and basal cells. These cells adhere to each other by cell adhesion apparatuses whose roles in hormone-dependent mammary gland development remain largely unknown. Here we identified a novel cell adhesion apparatus at the boundary between the luminal and basal cells in addition to desmosomes. This apparatus was formed by the trans-interaction between the cell adhesion molecules nectin-4 and nectin-1, which were expressed in the luminal and basal cells, respectively. Nectin-4 of this apparatus further cis-interacted with the prolactin receptor in the luminal cells to enhance the prolactin-induced prolactin receptor signaling for alveolar development with lactogenic differentiation. Thus, a novel nectin-mediated cell adhesion apparatus regulates the prolactin receptor signaling for mammary gland development.

  11. Associations of the 5-hydroxytryptamine (serotonin) receptor 1B gene (HTR1B) with alcohol, cocaine, and heroin abuse.

    Science.gov (United States)

    Cao, Jian; LaRocque, Emily; Li, Dawei

    2013-03-01

    Abnormal serotonergic pathways are implicated in numerous neuropsychiatric disorders including alcohol and drug dependence (abuse). The human 5-hydroxytryptamine (serotonin) receptor 1B, encoded by the HTR1B (5-HT1B) gene, is a presynaptic serotonin autoreceptor that plays an important role in regulating serotonin synthesis and release. Although there was evidence of associations of the HTR1B gene variants in the etiologies of substance use disorders, negative findings were also reported. To clarify the roles of commonly reported single nucleotide polymorphisms (SNPs) of the HTR1B gene underlying alcohol and drug dependence (abuse), we performed a meta-analysis based on the available genotype data from individual candidate gene-based association studies. Evidence of association was found between the functional SNP -161A>T (rs130058) and alcohol, cocaine, and heroin dependence (e.g., P = 0.03 and odds ratio (OR) = 1.2 (1.02, 1.42) in the combined European, Asian, African, and Hispanic populations). SNP -261T>G (rs11568817) also showed evidence of association but with different directions in Europeans and non-Europeans (e.g., P = 0.0018 with OR = 1.42 (1.14, 1.76) and P = 0.01 with ORs = 0.5 (0.3, 0.85), respectively). This meta-analysis supports the associations of HTR1B -261T>G and -161A>T with alcohol and drug abuse and further investigations are warranted in larger samples.

  12. Characteristics of stably expressed human dopamine D1a and D1b receptors: atypical behavior of the dopamine D1b receptor

    DEFF Research Database (Denmark)

    Pedersen, U B; Norby, B; Jensen, Anders A.

    1994-01-01

    Human dopamine D1a and D1b receptors were stably expressed in Baby Hamster Kidney (BHK) or Chinese Hamster Ovary (CHO) cells. [3H]SCH23390 saturation experiments indicated the presence of only a single binding site in the D1a expressing cell line with a Kd of 0.5 nM. In D1b expressing cell lines...... for these receptors. Besides SCH 23390, only NNC 112, fluphenazine and bulbocapnine were able to discriminate between the two states of the D1b receptor. In case of the D1a receptor, the Ki values obtained in binding experiments were very similar to Ki values obtained from inhibition of dopamine stimulated adenylyl...... cyclase. In the D1b expressing cell line, the Ki values obtained from inhibition of the dopamine stimulated adenylyl cyclase indicated a significantly better correlation with the state of the D1b receptor showing high affinity for antagonists. In agreement with observations from binding experiments...

  13. The Pafah1b complex interacts with the reelin receptor VLDLR.

    Directory of Open Access Journals (Sweden)

    Guangcheng Zhang

    Full Text Available Reelin is an extracellular protein that directs the organization of cortical structures of the brain through the activation of two receptors, the very low-density lipoprotein receptor (VLDLR and the apolipoprotein E receptor 2 (ApoER2, and the phosphorylation of Disabled-1 (Dab1. Lis1, the product of the Pafah1b1 gene, is a component of the brain platelet-activating factor acetylhydrolase 1b (Pafah1b complex, and binds to phosphorylated Dab1 in response to Reelin. Here we investigated the involvement of the whole Pafah1b complex in Reelin signaling and cortical layer formation and found that catalytic subunits of the Pafah1b complex, Pafah1b2 and Pafah1b3, specifically bind to the NPxYL sequence of VLDLR, but not to ApoER2. Compound Pafah1b1(+/-;Apoer2(-/- mutant mice exhibit a reeler-like phenotype in the forebrain consisting of the inversion of cortical layers and hippocampal disorganization, whereas double Pafah1b1(+/-;Vldlr(-/- mutants do not. These results suggest that a cross-talk between the Pafah1b complex and Reelin occurs downstream of the VLDLR receptor.

  14. Identification of bovine prolactin in seminal fluid, and expression and localization of the prolactin receptor and prolactin-inducible protein in the testis and epididymis of bulls exposed to ergot alkaloids.

    Science.gov (United States)

    Pratt, S L; Calcatera, S M; Stowe, H M; Dimmick, M A; Schrick, F N; Duckett, S K; Andrae, J G

    2015-03-01

    The objectives of this study were to determine (1) the presence and expression levels of bovine prolactin receptor (PRLR) and prolactin-inducible protein (PIP) in bovine testis and epididymis, and (2) the presence and concentrations of prolactin (PRL) present in seminiferous fluid in bulls consuming diets with (E+) or without (E-) ergot alkaloids. Bulls (n = 8) were sacrificed after 126 days (group A) of E+ or E- treatment or 60 days after all bulls (n = 6) were switched to the E- ration (group B). End point and real-time quantitative reverse transcription-polymerase chain reaction and immunohistochemistry were conducted on testis and epididymis samples to establish the presence and relative expression of PRLR and PIP. Seminal fluid samples obtained from bulls consuming E- and E+ diets were subjected to RIA for PRL. Both PIP and PRLR were present in testis and epididymis as determined by reverse transcription-polymerase chain reaction and immunohistochemistry. Prolactin-inducible protein mRNA abundance was affected by time of slaughter in testis and epididymis head, respectively (P Prolactin receptor mRNA expression was affected by time of slaughter in the epididymis (P < 0.05) and differed in testis samples because of treatment (P < 0.05). Radioimmunoassay establishes the presence of PRL in seminal fluid; however, differences in the concentration of PRL over two separate studies were inconsistent, possibly because of differences in diet. The presence and localization of the PRLR are consistent with expression data reported for other species, and the presence of PIP and PRL in seminal fluid is consistent with data generated in humans.

  15. Prolactin mediates neuroprotection against excitotoxicity in primary cell cultures of hippocampal neurons via its receptor.

    Science.gov (United States)

    Vergara-Castañeda, E; Grattan, D R; Pasantes-Morales, H; Pérez-Domínguez, M; Cabrera-Reyes, E A; Morales, T; Cerbón, M

    2016-04-01

    Recently it has been reported that prolactin (PRL) exerts a neuroprotective effect against excitotoxicity in hippocampus in the rat in vivo models. However, the exact mechanism by which PRL mediates this effect is not completely understood. The aim of our study was to assess whether prolactin exerts neuroprotection against excitotoxicity in an in vitro model using primary cell cultures of hippocampal neurons, and to determine whether this effect is mediated via the prolactin receptor (PRLR). Primary cell cultures of rat hippocampal neurons were used in all experiments, gene expression was evaluated by RT-qPCR, and protein expression was assessed by Western blot analysis and immunocytochemistry. Cell viability was assessed by using the MTT method. The results demonstrated that PRL treatment of neurons from primary cultures did not modify cell viability, but that it exerted a neuroprotective effect, with cells treated with PRL showing a significant increase of viability after glutamate (Glu)--induced excitotoxicity as compared with neurons treated with Glu alone. Cultured neurons expressed mRNA for both PRL and its receptor (PRLR), and both PRL and PRLR expression levels changed after the excitotoxic insult. Interestingly, the PRLR protein was detected as two main isoforms of 100 and 40 kDa as compared with that expressed in hypothalamic cells, which was present only as a 30 kDa variant. On the other hand, PRL was not detected in neuron cultures, either by western blot or by immunohistochemistry. Neuroprotection induced by PRL was significantly blocked by specific oligonucleotides against PRLR, thus suggesting that the PRL role is mediated by its receptor expressed in these neurons. The overall results indicated that PRL induces neuroprotection in neurons from primary cell cultures.

  16. Effects of deletion of the prolactin receptor on ovarian gene expression

    Directory of Open Access Journals (Sweden)

    Kelly Paul A

    2003-02-01

    Full Text Available Abstract Prolactin (PRL exerts pleiotropic physiological effects in various cells and tissues, and is mainly considered as a regulator of reproduction and cell growth. Null mutation of the PRL receptor (R gene leads to female sterility due to a complete failure of embryo implantation. Pre-implantatory egg development, implantation and decidualization in the mouse appear to be dependent on ovarian rather than uterine PRLR expression, since progesterone replacement permits the rescue of normal implantation and early pregnancy. To better understand PRL receptor deficiency, we analyzed in detail ovarian and corpora lutea development of PRLR-/- females. The present study demonstrates that the ovulation rate is not different between PRLR+/+ and PRLR-/- mice. The corpus luteum is formed but an elevated level of apoptosis and extensive inhibition of angiogenesis occur during the luteal transition in the absence of prolactin signaling. These modifications lead to the decrease of LH receptor expression and consequently to a loss of the enzymatic cascades necessary to produce adequate levels of progesterone which are required for the maintenance of pregnancy.

  17. Nectin-4 Co-stimulates the Prolactin Receptor by Interacting with SOCS1 and Inhibiting Its Activity on the JAK2-STAT5a Signaling Pathway.

    Science.gov (United States)

    Maruoka, Masahiro; Kedashiro, Shin; Ueda, Yuki; Mizutani, Kiyohito; Takai, Yoshimi

    2017-03-03

    Cell surface cytokine receptors are regulated by their cis-interacting stimulatory and inhibitory co-receptors. We previously showed that the immunoglobulin-like cell adhesion molecule nectin-4 cis-interacts with the prolactin receptor through the extracellular region and stimulates prolactin-induced prolactin receptor activation and signaling, resulting in alveolar development in the mouse mammary gland. However, it remains unknown how this interaction stimulates these effects. We show here that the cis-interaction of the extracellular region of nectin-4 with the prolactin receptor was not sufficient for eliciting these effects and that nectin-4's cytoplasmic region was also required for eliciting these effects. The cytoplasmic region of nectin-4 directly interacted with suppressor of cytokine signaling (SOCS) 1, but not SOCS3, JAK2, or STAT5a, and inhibited SOCS1's interaction with JAK2, eventually resulting in the increased phosphorylation of STAT5a. The juxtamembrane region of nectin-4 interacts with the Src homology 2 domain of SOCS1. Both the interactions of nectin-4 with the extracellular region of the prolactin receptor and the interactions of SOCS1 with nectin-4's cytoplasmic region were required for the stimulatory effect of nectin-4 on the prolactin-induced prolactin receptor activation. The third immunoglobulin-like domain of nectin-4 and the second fibronectin type-III domain of the prolactin receptor were involved in this cis-interaction, and both the extracellular and transmembrane regions of nectin-4 and the prolactin receptor were required for this direct interaction. These results indicate that nectin-4 serves as a stimulatory co-receptor for the prolactin receptor by regulating the feedback inhibition of SOCS1 in the JAK2-STAT5a signaling pathway.

  18. Vasopressin V1a and V1b receptors: from molecules to physiological systems.

    Science.gov (United States)

    Koshimizu, Taka-aki; Nakamura, Kazuaki; Egashira, Nobuaki; Hiroyama, Masami; Nonoguchi, Hiroshi; Tanoue, Akito

    2012-10-01

    The neurohypophysial hormone arginine vasopressin (AVP) is essential for a wide range of physiological functions, including water reabsorption, cardiovascular homeostasis, hormone secretion, and social behavior. These and other actions of AVP are mediated by at least three distinct receptor subtypes: V1a, V1b, and V2. Although the antidiuretic action of AVP and V2 receptor in renal distal tubules and collecting ducts is relatively well understood, recent years have seen an increasing understanding of the physiological roles of V1a and V1b receptors. The V1a receptor is originally found in the vascular smooth muscle and the V1b receptor in the anterior pituitary. Deletion of V1a or V1b receptor genes in mice revealed that the contributions of these receptors extend far beyond cardiovascular or hormone-secreting functions. Together with extensively developed pharmacological tools, genetically altered rodent models have advanced the understanding of a variety of AVP systems. Our report reviews the findings in this important field by covering a wide range of research, from the molecular physiology of V1a and V1b receptors to studies on whole animals, including gene knockout/knockdown studies.

  19. Combined sodium ion sensitivity in agonist binding and internalization of vasopressin V1b receptors.

    Science.gov (United States)

    Koshimizu, Taka-Aki; Kashiwazaki, Aki; Taniguchi, Junichi

    2016-05-03

    Reducing Na(+) in the extracellular environment may lead to two beneficial effects for increasing agonist binding to cell surface G-protein coupled receptors (GPCRs): reduction of Na(+)-mediated binding block and reduce of receptor internalization. However, such combined effects have not been explored. We used Chinese Hamster Ovary cells expressing vasopressin V1b receptors as a model to explore Na(+) sensitivity in agonist binding and receptor internalization. Under basal conditions, a large fraction of V1b receptors is located intracellularly, and a small fraction is in the plasma membrane. Decreases in external Na(+) increased cell surface [(3)H]AVP binding and decreased receptor internalization. Substitution of Na(+) by Cs(+) or NH4(+) inhibited agonist binding. To suppress receptor internalization, the concentration of NaCl, but not of CsCl, had to be less than 50 mM, due to the high sensitivity of the internalization machinery to Na(+) over Cs(+). Iso-osmotic supplementation of glucose or NH4Cl maintained internalization of the V1b receptor, even in a low-NaCl environment. Moreover, iodide ions, which acted as a counter anion, inhibited V1b agonist binding. In summary, we found external ionic conditions that could increase the presence of high-affinity state receptors at the cell surface with minimum internalization during agonist stimulations.

  20. Could the 5-HT1B receptor inverse agonism affect learning consolidation?

    Science.gov (United States)

    Meneses, A

    2001-03-01

    Diverse evidence indicates that, the 5-HT system might play a role in learning and memory, since it occurs in brain areas mediating such processes and 5-HT drugs modulate them. Hence in this work, in order to explore further 5-HT involvement on learning and memory 5-HT1B receptors' role is investigated. Evidence indicates that SB-224289 (a 5-HT1B receptor inverse agonist) post-training injection facilitated learning consolidation in an associative autoshaping learning task, this effect was partially reversed by GR 127935 (a 5-HT1B/1D receptor antagonist), but unaffected by MDL 100907 (a 5-HT2A receptor antagonist) or ketanserin (a 5-HT1D/2A/7 receptor antagonist) at low doses. Moreover, SB-224289 antagonized the learning deficit produced by TFMPP (a 5-HT1A/1B/1D/2A/2C receptor agonist), GR 46611 (a 5-HT1A/1B/1D receptor agonist), mCPP (a 5-HT2A/2C/3/7 receptor agonist/antagonist) or GR 127935 (at low dose). SB-224289 did not alter the 8-OH-DPAT (a 5-HT1A/7 receptor agonist) learning facilitatory effect. SB-224289 eliminated the deficit learning produced by the anticholinergic muscarinic scopolamine or the glutamatergic antagonist dizocilpine. Administration of both, GR 127935 (5mg/kg) plus ketanserin (0.01 mg/kg) did not modify learning consolidation; nevertheless, when ketanserin dose was increased (0.1-1.0mg/kg) and SB-224289 dose was maintained constant, a learning facilitation effect was observed. Notably, SB-224289 at 1.0mg/kg potentiated a subeffective dose of the 5-HT1B/1D receptor agonist/antagonist mixed GR 127935, which facilitated learning consolidation and this effect was abolished by ketanserin at a higher dose. Collectively, the data confirm and extend the earlier findings with GR 127935 and the effects of non-selective 5-HT(1B) receptor agonists. Clearly 5-HT1B agonists induced a learning deficit which can be reversed with SB-224289. Perhaps more importantly, SB-224289 enhances learning consolidation when given alone and can reverse the deficits

  1. A comparison of two semi-mechanistic models for prolactin release and prediction of receptor occupancy following administration of dopamine D2 receptor antagonists in rats.

    Science.gov (United States)

    Taneja, Amit; Vermeulen, An; Huntjens, Dymphy R H; Danhof, Meindert; De Lange, Elizabeth C M; Proost, Johannes H

    2016-10-15

    We compared the model performance of two semi-mechanistic pharmacokinetic-pharmacodynamic models, the precursor pool model and the agonist-antagonist interaction model, to describe prolactin response following the administration of the dopamine D2 receptor antagonists risperidone, paliperidone or remoxipride in rats. The time course of pituitary dopamine D2 receptor occupancy was also predicted. Male Wistar rats received a single dose (risperidone, paliperidone, remoxipride) or two consecutive doses (remoxipride). Population modeling was applied to fit the pool and interaction models to the prolactin data. The pool model was modified to predict the time course of pituitary D2 receptor occupancy. Unbound plasma concentrations of the D2 receptor antagonists were considered the drivers of the prolactin response. Both models were used to predict prolactin release following multiple doses of paliperidone. Both models described the data well and model performance was comparable. Estimated unbound EC50 for risperidone and paliperidone was 35.1nM (relative standard error 51%) and for remoxipride it was 94.8nM (31%). KI values for these compounds were 11.1nM (21%) and 113nM (27%), respectively. Estimated pituitary D2 receptor occupancies for risperidone and remoxipride were comparable to literature findings. The interaction model better predicted prolactin profiles following multiple paliperidone doses, while the pool model predicted tolerance better. The performance of both models in describing the prolactin profiles was comparable. The pool model could additionally describe the time course of pituitary D2 receptor occupancy. Prolactin response following multiple paliperidone doses was better predicted by the interaction model.

  2. Interaction of CPCCOEt with a chimeric mGlu1b and calcium sensing receptor

    DEFF Research Database (Denmark)

    Bräuner-Osborne, H; Jensen, Anders A.; Krogsgaard-Larsen, P

    1999-01-01

    7-Hydroxyiminocyclopropan[b]chromen-1a-carboxylic acid ethyl ester (CPCCOEt) has previously been shown to be a selective non-competitive antagonist at the metabotropic glutamate (mGlu) receptor subtype 1. In this study we have tested the effect of CPCCOEt on mGlu1b, the calcium sensing receptor (...

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

    Science.gov (United States)

    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

  4. Trafficking of α1B-adrenergic receptor mediated by inverse agonist in living cells

    Institute of Scientific and Technical Information of China (English)

    MingXU; Ying-huaGUAN; NingXU; Zhang-yiLIANG; Shu-yiWang; YaoSONG; Chi-deHAN; Xin-shengZHAO; You-yiZHANG

    2005-01-01

    AIM The project is aimed at understanding the action of inverse agonist at single molecule level and capturing the real time picture of molecular behavior of α1B-adrenergic receptor (AR) mediated by inverse agonist in living cells by single molecule detection (SMD). METHODS The location and distribution of α1B-AR was detected by laser confocal and whole cell 3H-prazosin binding assay. Dynamic imaging of BODIPY-FL-labeled prazosin (Praz), specific antagonist of (1-AR, was observed in α1B-AR stably expressed human embryonic kidney 293 (HEK293) living cells. The detection of real-time dynamic behaviors of AR was achieved by using fluorescence-labeled AR and its ligand combined with SMD techniques. RESULTS α1B-AR was predominantly distributed on the cell surface and 8.2% of the total receptors were located in cytosol.

  5. Investigation of Prolactin Receptor Activation and Blockade Using Time-Resolved Fluorescence Resonance Energy Transfer

    Directory of Open Access Journals (Sweden)

    Estelle eTallet

    2011-09-01

    Full Text Available The prolactin receptor (PRLR is emerging as a therapeutic target in oncology. Knowledge-based drug design led to the development of a pure PRLR antagonist (Del1-9-G129R-hPRL that was recently shown to prevent PRL-induced mouse prostate tumorogenesis. In humans, the first gain-of-function mutation of the PRLR (PRLRI146L was recently identified in breast tumor patients. At the molecular level, the actual mechanism of action of these two novel players in the PRL system remains elusive. In this study, we addressed whether constitutive PRLR activation (PRLRI146L or PRLR blockade (antagonist involved alteration of receptor oligomerization and/or of inter-chain distances compared to unstimulated and PRL-stimulated PRLR. Using a combination of various biochemical and spectroscopic approaches (co-IP, blue-native electrophoresis, BRET1, we demonstrated that preformed PRLR homodimers are altered neither by PRL- or I146L-induced receptor triggering, nor by antagonist-mediated blockade. These findings were confirmed using a novel time-resolved fluorescence resonance energy transfer (TR-FRET technology that allows monitoring distance changes between cell-surface tagged receptors. This technology revealed that PRLR blockade or activation did not involve detectable distance changes between extracellular domains of receptor chains within the dimer. This study merges with our previous structural investigations suggesting that the mechanism of PRLR activation solely involves intermolecular contact adaptations leading to subtle intramolecular rearrangements.

  6. The prolactin response to sulpiride in major depression: the role of the D2 receptor in depression.

    Science.gov (United States)

    Verbeeck, W J; Berk, M; Paiker, J; Jersky, B

    2001-06-01

    Multiple lines of investigations have implicated the role of the dopaminergic system in depression. The aim of the study was to characterise the Dopamine D2 receptor sensitivity status in depressed patients versus controls by means of a novel neuro-endocrine challenge test, the prolactin response to sulpiride. In this intervention, ten patients and ten age matched male volunteers were studied. The patients were diagnosed according to DSM-IV criteria, and Montgomery Asberg and Zung scales were done. There was no significant difference in baseline levels of prolactin between the depressed and control groups. Significantly higher prolactin levels after sulpiride challenge were however found in depressed patients than controls at all time points after sulpiride administration. This neuroendocrine challenge paradigm suggests that the prolactin response to sulpiride, a D2 receptor antagonist, is enhanced in depression, which suggests that this receptor might be supersensitive in depression compared to controls. This adds to the data implicating the dopaminergic system in the pathophysiology of depression, and suggests that dopaminergic mechanisms might be a target of therapeutic interest.

  7. Nature's knockout: the Mel1b receptor is not necessary for reproductive and circadian responses to melatonin in Siberian hamsters.

    Science.gov (United States)

    Weaver, D R; Liu, C; Reppert, S M

    1996-11-01

    The pineal hormone melatonin regulates seasonal reproduction and influences the timing of circadian rhythms. The Mel1a and Mel1b receptors are the high-affinity melatonin receptors present in mammals. Unexpectedly, the Mel1b receptor gene of the Siberian hamster, Phodopus sungorus, cannot encode a functional receptor; two nonsense mutations are present within the coding region. Southern blot analysis indicates that this is a single copy gene. The Mel1b receptor gene is nonfunctional in outbred populations of P. sungorus and Phodopus campbelli. Siberian hamsters lacking a functional Mel1b receptor nevertheless show seasonal reproductive and circadian responses to melatonin, indicating that the Mel1b receptor is not necessary for these responses. These data support the hypothesis that the Mel1a receptor, which does encode a functional receptor in this species, mediates reproductive and circadian responses to melatonin.

  8. Preclinical pharmacology and pharmacokinetics of AZD3783, a selective 5-hydroxytryptamine 1B receptor antagonist.

    Science.gov (United States)

    Zhang, Minli; Zhou, Diansong; Wang, Yi; Maier, Donna L; Widzowski, Daniel V; Sobotka-Briner, Cynthia D; Brockel, Becky J; Potts, William M; Shenvi, Ashok B; Bernstein, Peter R; Pierson, M Edward

    2011-11-01

    The preclinical pharmacology and pharmacokinetic properties of (2R)-6-methoxy-8-(4-methylpiperazin-1-yl)-N-(4-morpholin-4-ylphenyl)chromane-2-carboxamide (AZD3783), a potent 5-hydroxytryptamine 1B (5-HT(1B)) receptor antagonist, were characterized as part of translational pharmacokinetic/pharmacodynamic hypothesis testing in human clinical trials. The affinity of AZD3783 to the 5-HT(1B) receptor was measured in vitro by using membrane preparations containing recombinant human or guinea pig 5-HT(1B) receptors and in native guinea pig brain tissue. In vivo antagonist potency of AZD3783 for the 5HT(1B) receptor was investigated by measuring the blockade of 5-HT(1B) agonist-induced guinea pig hypothermia. The anxiolytic-like potency was assessed using the suppression of separation-induced vocalization in guinea pig pups. The affinity of AZD3783 for human and guinea pig 5-HT(1B) receptor (K(i), 12.5 and 11.1 nM, respectively) was similar to unbound plasma EC(50) values for guinea pig receptor occupancy (11 nM) and reduction of agonist-induced hypothermia (18 nM) in guinea pig. Active doses of AZD3783 in the hypothermia assay were similar to doses that reduced separation-induced vocalization in guinea pig pups. AZD3783 demonstrated favorable pharmacokinetic properties. The predicted pharmacokinetic parameters (total plasma clearance, 6.5 ml/min/kg; steady-state volume of distribution, 6.4 l/kg) were within 2-fold of the values observed in healthy male volunteers after a single 20-mg oral dose. This investigation presents a direct link between AZD3783 in vitro affinity and in vivo receptor occupancy to preclinical disease model efficacy. Together with predicted human pharmacokinetic properties, we have provided a model for the quantitative translational pharmacology of AZD3783 that increases confidence in the optimal human receptor occupancy required for antidepressant and anxiolytic effects in patients.

  9. Contribution of brain serotonin subtype 1B receptors in levodopa-induced motor complications.

    Science.gov (United States)

    Morin, Nicolas; Morissette, Marc; Grégoire, Laurent; Rajput, Alex; Rajput, Ali H; Di Paolo, Thérèse

    2015-12-01

    L-DOPA-induced dyskinesias (LID) are abnormal involuntary movements limiting the chronic use of L-DOPA, the main pharmacological treatment of Parkinson's disease. Serotonin receptors are implicated in the development of LID and modulation of basal ganglia 5-HT1B receptors is a potential therapeutic alternative in Parkinson's disease. In the present study, we used receptor-binding autoradiography of the 5-HT1B-selective radioligand [3H]GR125743 to investigate possible contributions of changes in ligand binding of this receptor in LID in post-mortem brain specimens from Parkinson's disease patients (n=14) and control subjects (n=11), and from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned monkeys treated with saline (n=5), L-DOPA (n=4) or L-DOPA+2-methyl-6-(phenylethynyl)pyridine (MPEP) (n=5), and control monkeys (n=4). MPEP is the prototypal metabotropic glutamate 5 (mGlu5) receptor antagonist and has been shown to reduce the development of LID in these monkeys in a chronic treatment of one month. [3H]GR125743 specific binding to striatal and pallidal 5-HT1B receptors respectively were only increased in L-DOPA-treated MPTP monkeys (dyskinetic monkeys) as compared to controls, saline and L-DOPA+MPEP MPTP monkeys; dyskinesias scores correlated positively with this binding. Parkinson's disease patients with motor complications (L-DOPA-induced dyskinesias and wearing-off) had higher [3H]GR125743 specific binding compared to those without motor complications and controls in the basal ganglia. Reduction of motor complications was associated with normal striatal 5-HT1B receptors, suggesting the potential of this receptor for the management of motor complications in Parkinson's disease.

  10. The arginine vasopressin V1b receptor gene and prosociality: Mediation role of emotional empathy.

    Science.gov (United States)

    Wu, Nan; Shang, Siyuan; Su, Yanjie

    2015-09-01

    The vasopressin V1b receptor (AVPR1B) gene has been shown to be closely associated with bipolar disorder and depression. However, whether it relates to positive social outcomes, such as empathy and prosocial behavior, remains unknown. This study explored the possible role of the AVPR1B gene rs28373064 in empathy and prosociality. A total of 256 men, who were genetically unrelated, non-clinical ethnic Han Chinese college students, participated in the study. Prosociality was tested by measuring the prosocial tendencies of cognitive and emotional empathy using the Interpersonal Reactivity Index (IRI). The single nucleotide polymorphism (SNP), rs28373064, was genotyped using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The results suggest that the AVPR1B gene rs28373064 is linked to emotional empathy and prosociality. The mediation analysis indicated that the effect of the AVPR1B gene on prosociality might be mediated by emotional empathy. This study demonstrated the link between the AVPR1B gene and prosociality and provided evidence that emotional empathy might mediate the relation between the AVPR1B gene and prosociality.

  11. Bidirectional regulation of emotional memory by 5-HT1B receptors involves hippocampal p11.

    Science.gov (United States)

    Eriksson, T M; Alvarsson, A; Stan, T L; Zhang, X; Hascup, K N; Hascup, E R; Kehr, J; Gerhardt, G A; Warner-Schmidt, J; Arango-Lievano, M; Kaplitt, M G; Ogren, S O; Greengard, P; Svenningsson, P

    2013-10-01

    Cognitive impairments are common in depression and involve dysfunctional serotonin neurotransmission. The 5-HT1B receptor (5-HT(1B)R) regulates serotonin transmission, via presynaptic receptors, but can also affect transmitter release at heterosynaptic sites. This study aimed at investigating the roles of the 5-HT(1B)R, and its adapter protein p11, in emotional memory and object recognition memory processes by the use of p11 knockout (p11KO) mice, a genetic model for aspects of depression-related states. 5-HT(1B)R agonist treatment induced an impairing effect on emotional memory in wild type (WT) mice. In comparison, p11KO mice displayed reduced long-term emotional memory performance. Unexpectedly, 5-HT(1B)R agonist stimulation enhanced memory in p11KO mice, and this atypical switch was reversed after hippocampal adeno-associated virus mediated gene transfer of p11. Notably, 5-HT(1B)R stimulation increased glutamatergic neurotransmission in the hippocampus in p11KO mice, but not in WT mice, as measured by both pre- and postsynaptic criteria. Magnetic resonance spectroscopy demonstrated global hippocampal reductions of inhibitory GABA, which may contribute to the memory enhancement and potentiation of pre- and post-synaptic measures of glutamate transmission by a 5-HT(1B)R agonist in p11KO mice. It is concluded that the level of hippocampal p11 determines the directionality of 5-HT(1B)R action on emotional memory processing and modulates hippocampal functionality. These results emphasize the importance of using relevant disease models when evaluating the role of serotonin neurotransmission in cognitive deficits related to psychiatric disorders.

  12. Antisense mRNA for NPY-Y1 receptor in the medial preoptic area increases prolactin secretion

    Directory of Open Access Journals (Sweden)

    N.A. Silveira

    1999-09-01

    Full Text Available We investigated the participation of neuropeptide Y-Y1 receptors within the medial preoptic area in luteinizing hormone, follicle-stimulating hormone and prolactin release. Four bilateral microinjections of sense (control or antisense 18-base oligonucleotides of messenger ribonucleic acid (mRNA (250 ng corresponding to the NH2-terminus of the neuropeptide Y1 receptor were performed at 12-h intervals for two days into the medial preoptic area of ovariectomized Wistar rats (N = 16, weighing 180 to 200 g, treated with estrogen (50 µg and progesterone (25 mg two days before the experiments between 8.00 and 10:00 a.m. Blockade of Y1 receptor synthesis in the medial preoptic area by the antisense mRNA did not change plasma luteinizing hormone or follicle-stimulating hormone but did increase prolactin from 19.6 ± 5.9 ng/ml in the sense group to 52.9 ± 9.6 ng/ml in the antisense group. The plasma hormones were measured by radioimmunoassay and the values are reported as mean ± SEM. These data suggest that endogenous neuropeptide Y in the medial preoptic area has an inhibitory action on prolactin secretion through Y1 receptors.

  13. Subarachnoid hemorrhage-induced upregulation of the 5-HT1B receptor in cerebral arteries in rats

    DEFF Research Database (Denmark)

    Hansen-Schwartz, Jacob; Hoel, Natalie Løvland; Xu, Cang-Bao;

    2003-01-01

    in vitro pharmacological method molecularly by performing quantitative real-time reverse transcription-polymerase chain reaction (PCR). In the MCA and BA the 5-HT1B receptor was upregulated, as determined through both functional and molecular analysis. In response to selective 5-HT1 receptor agonists both...... RNA coding for the 5-HT1B receptor as determined by quantitative real-time PCR. In the PCoA no upregulation of the 5-HT1B receptor was observed. CONCLUSIONS: Changes in the receptor phenotype in favor of contractile receptors may well represent the end stage in a sequence of events leading from SAH...

  14. Prolactin receptor-mediated internalization of imaging agents detects epithelial ovarian cancer

    Science.gov (United States)

    Sundaram, Karthik M.

    Epithelial ovarian cancer (EOC) has the highest mortality rate of all gynecologic malignant tumors. Diagnosis of epithelial ovarian cancer (EOC) presents two main challenges. The first challenge is detecting low volume (prolactin receptor (PRLR) - a cell surface tyrosine kinase receptor that is over-expressed in moderate to high levels on > 98% of epithelial ovarian cancers. Upon binding of native ligands to PRLR, the ligand:PRLR complex is internalized by cells. By conjugating gadolinium-chelates, molecules normally used as contrast agents diagnostically, to human placental lactogen (hPL), a native ligand of PRLR, we show that MRI becomes highly sensitive and specific for detecting PRLR (+) tumors in a nude mouse model of EOC. We further establish the adaptability of this approach for fluorescence-based imaging techniques using an hPL conjugated Cy5.5 dye. We conclude that molecular imaging of PRLR with hPL-conjugated imaging agents can address the current challenges that limit EOC diagnosis.

  15. Structure-based discovery of selective serotonin 5-HT(1B) receptor ligands.

    Science.gov (United States)

    Rodríguez, David; Brea, José; Loza, María Isabel; Carlsson, Jens

    2014-08-05

    The development of safe and effective drugs relies on the discovery of selective ligands. Serotonin (5-hydroxytryptamine [5-HT]) G protein-coupled receptors are therapeutic targets for CNS disorders but are also associated with adverse drug effects. The determination of crystal structures for the 5-HT1B and 5-HT2B receptors provided an opportunity to identify subtype selective ligands using structure-based methods. From docking screens of 1.3 million compounds, 22 molecules were predicted to be selective for the 5-HT1B receptor over the 5-HT2B subtype, a requirement for safe serotonergic drugs. Nine compounds were experimentally verified as 5-HT1B-selective ligands, with up to 300-fold higher affinities for this subtype. Three of the ligands were agonists of the G protein pathway. Analysis of state-of-the-art homology models of the two 5-HT receptors revealed that the crystal structures were critical for predicting selective ligands. Our results demonstrate that structure-based screening can guide the discovery of ligands with specific selectivity profiles.

  16. Expression of autocrine prolactin and the short isoform of prolactin receptor are associated with inflammatory response and apoptosis in monocytes stimulated with Mycobacterium bovis proteins.

    Science.gov (United States)

    López-Rincón, Gonzalo; Mancilla, Raúl; Pereira-Suárez, Ana L; Martínez-Neri, Priscila A; Ochoa-Zarzosa, Alejandra; Muñoz-Valle, José Francisco; Estrada-Chávez, Ciro

    2015-06-01

    Increased levels of prolactin (PRL) have recently been associated with carcinogenesis and the exacerbation of autoimmune diseases, and might be involved in the progression of tuberculosis (TB). To investigate the relationship between PRL and prolactin receptor (PRLr) expression with inflammatory response and apoptosis in monocytes, we used THP-1 cells stimulated with antigens of the Mycobacterium bovis AN5 strain culture filtrate protein (CFP-M. bovis). Western blot (WB), real-time Polymerase chain reaction (PCR), and immunocytochemistry were performed to identify both PRL and PRLr molecules. PRL bioactivity and proinflammatory cytokine detection were assessed. The results showed that PRL and PRLr messenger RNA (mRNA) were synthesized in THP-1 monocytes induced with CFP-M. bovis at peaks of 176- and 404-fold, respectively. PRL forms of 60 and 80kDa and PRLr isoforms of 40, 50, and 65kDa were also identified as time-dependent, while 60-kDa PRL, as well as 40-, and 50-kDa PRLr, were found as soluble forms in culture media and later in the nucleus of THP-1 monocytes. PRL of 60kDa released by monocytes exhibited bioactivity in Nb2 cells, and both synthesized PRL and synthesized PRLr were related with nitrite and proinflammatory cytokine levels proapoptotic activity in CFP-M. bovis-induced monocytes. Our results suggest the overexpression of a full-autocrine loop of PRL and PRLr in monocytes that enhances the inflammatory response and apoptosis after priming with M. bovis antigens.

  17. Oestrogen requires the insulin-like growth factor-I receptor for stimulation of prolactin synthesis via mitogen-activated protein kinase.

    Science.gov (United States)

    Arroba, A I; Frago, L M; Argente, J; Chowen, J A

    2005-02-01

    Sex steroids and growth factors interact at the intracellular level in a variety of tissues to control numerous physiological functions. Oestrogen is known to stimulate prolactin synthesis and secretion, but the effect of insulin-like growth factor (IGF)-I is less clear. We used GH3 cells, a somatolactotroph cell line, to study the interaction of 17beta-oestradiol (E(2)) and IGF-I on prolactin protein levels and the intracellular mechanisms involved. Cell cultures were treated with E(2) (10 nM) and/or IGF-I (10 ng/ml) for 8 h. The real-time reverse transcriptase-polymerase chain reaction, Western blot and enzyme-immunoassay were used to determine changes in prolactin mRNA and protein levels. At this time-point, there were no significant changes in cell number, prolactin mRNA expression, or the amount of secreted prolactin. However, E(2) increased intracellular prolactin concentrations. IGF-I alone had no effect, but blocked the stimulatory effect of E(2). MAPK (ERK1/2) activation, as determined by Western blot analysis, increased with both E(2) and IGF-I, but not with the combination of these factors. The MAPK inhibitor PD98059 blocked the ability of E(2) to increase intracellular prolactin concentrations. Similarly, the IGF-I receptor antagonist, JB1, blocked the effect of E(2) on prolactin synthesis and MAPK activation, as did the oestrogen receptor antagonist ICI182 780. These results suggest that, to stimulate prolactin synthesis, E(2) activates the MAPK cascade and that this requires the presence of both oestrogen and IGF-I receptors.

  18. GENETIC VARIATION IN THE ALPHA1B - ADRENERGIC RECEPTOR AND VASCULAR RESPONSE

    Science.gov (United States)

    Adefurin, Abiodun; Ghimire, Laxmi V.; Kohli, Utkarsh; Muszkat, Mordechai; Sofowora, Gbenga G.; Li, Chun; Levinson, Rebecca T.; Paranjape, Sachin Y.; Stein, C. Michael; Kurnik, Daniel

    2016-01-01

    α1B- adrenergic receptors contribute to vasoconstriction in humans. We tested the hypothesis that variation in the ADRA1B gene contributes to interindividual variability and ethnic differences in adrenergic vasoconstriction. We measured dorsal hand vein responses to increasing doses of phenylephrine in 64 Caucasians and 41 African-Americans and genotyped 34 ADRA1B variants. We validated findings in another model of catecholamine-induced vasoconstriction, the increase in mean arterial pressure (ΔMAP) during a cold pressor test (CPT). One ADRA1B variant, rs10070745, present in 14 African-American heterozygotes but not in Caucasians, was associated with a lower phenylephrine ED50 (geometric mean [95% CI], 144 [69–299] ng/ml) compared to 27 African-American non-carriers (208 [130–334] ng/ml; P=0.015) and contributed to the ethnic differences in ED50. The same variant was also associated with a greater ΔMAP during CPT (P=0.008). In conclusion, ADRA1B rs10070745 was significantly associated with vasoconstrictor responses after adrenergic stimulation and contributed to the ethnic difference in phenylephrine sensitivity. PMID:27089938

  19. Regulation of prolactin receptor (PRLR) gene expression in insulin-producing cells. Prolactin and growth hormone activate one of the rat prlr gene promoters via STAT5a and STAT5b

    DEFF Research Database (Denmark)

    Galsgaard, E D; Møldrup, Annette; Nielsen, Jens Høiriis

    1999-01-01

    Expression of the prolactin receptor (PRLR) gene is increased in pancreatic islets during pregnancy and in vitro in insulin-producing cells by growth hormone (GH) and prolactin (PRL). The 5'-region of the rat PRLR gene contains at least three alternative first exons that are expressed tissue......-specifically because of differential promoter usage. We show by reverse transcription-polymerase chain reaction analysis that both exon 1A- and exon 1C-containing PRLR transcripts are expressed in rat islets and that human (h)GH, ovine (o)PRL, and bovine (b)GH increase exon 1A expression 6.5 +/- 0. 8-fold, 6.8 +/- 0...

  20. PROGRESS OF STUDIES ON PROLACTIN GENE AND PROLACTIN RECEPTOR GENE IN DAIRY CATTLE%奶牛催乳素(PRL)及其受体(PRLR)基因研究进展

    Institute of Scientific and Technical Information of China (English)

    郭彦斌; 杨海玲; 王慧

    2009-01-01

    催乳素(prolactin)参与了很多生理活动,包括乳蛋白的合成、免疫活动的调节、促进生殖器官的发育、维持渗透压的平衡以及一些生理行为.催乳素要行使其生物学功能必须与其受体(prolactin receptor)结合.本文就PRL基因及其受体PRLR基因的结构、功能以及在奶牛上的研究进展作一综述.

  1. Increased expression of 5-HT(1B) receptors by Herpes simplex virus gene transfer in septal neurons: New in vitro and in vivo models to study 5-HT(1B) receptor function.

    Science.gov (United States)

    Riegert, Céline; Rothmaier, Anna Katharina; Leemhuis, Jost; Sexton, Timothy J; Neumaier, John F; Cassel, Jean-Christophe; Jackisch, Rolf

    2008-07-01

    Serotonergic modulation of acetylcholine (ACh) release after neuron-specific increase of the expression of 5-HT(1B) receptors by gene transfer was studied in vitro and in vivo. The increased expression of the 5-HT(1B) receptor in vitro was induced by treating rat primary fetal septal cell cultures for 3 days with a viral vector inducing the expression of green fluorescent protein (GFP) vector alone, or, in addition, of 5-HT(1B) receptors (HA1B/GFP vector). The transfection resulted in a high number of GFP-positive cells, part of which being immunopositive for choline acetyltransferase. In HA1B/GFP-cultures (vs. GFP-cultures), electrically evoked ACh release was significantly more sensitive to the inhibitory action of the 5-HT(1B) agonist CP-93,129. Increased expression of the 5-HT(1B) receptor in vivo was induced by stereotaxic injections of the vectors into the rat septal region. Three days later, electrically evoked release of ACh in hippocampal slices of HA1B/GFP-treated rats was lower than in their GFP-treated counterparts, showing a higher inhibitory efficacy of endogenous 5-HT on cholinergic terminals after transfection. Moreover, CP-93,129 had a higher inhibitory potency. In conclusion, the HA1B/GFP vector reveals a useful tool to induce a targeted increase of 5-HT(1B) heteroreceptors on cholinergic neurons in selected CNS regions, which provides interesting perspectives for functional approaches at more integrated levels.

  2. Gene expression of lymphocyte prolactin receptor was suppressed in lactating mothers.

    Science.gov (United States)

    Maeda, Hironobu; Izumi, Shun-ichiro; Kato, Yukio; Cai, Li-yi; Kato, Takako; Suzuki, Takahiro; Nakamura, Eri; Sugiyama, Taro; Fuda, Takayo; Takahashi, Kazumi; Kondo, Akane; Matsumoto, Tadashi; Ishimoto, Hitoshi

    2010-07-20

    Prolactin (PRL) receptor (PRL-R) was proven to be ubiquitously expressed by cells in the immune system, while the physiological role of PRL was established in milk production in mammary glands. We analyzed the mRNA content of PRL-R in human lymphocytes in normo- and hyperprolactinemic conditions to document the presence of functioning PRL-R of human lymphocytes. Blood samples were obtained prior to treatment, and with written informed consent, from outpatients with ovarian dysfunction and hyperprolactinemia (n = 8; 19 ~ 41 y/o), from breast-feeding mothers after normal delivery (n = 12; 27 ~ 36 y/o), and from healthy volunteers: men (n = 9; 33 ~ 40 y/o) and women (n = 9; 26 ~ 36 y/o). Subsequently, total RNA was prepared from the lymphocytes separated. The quantity of PRL-R mRNA was examined by reverse transcription and polymerase chain reaction and normalized with a simultaneously measured amount of b actin. The resultant mRNA level of PRL-R was analyzed for its correlation with serum concentration of PRL measured by immunoassay. PRL-R mRNA levels of lymphocytes were significantly suppressed in lactating mothers, while there was a statistically significant negative correlation between PRL-R mRNA and serum PRL levels. However, there was no significant difference of PRL-R mRNA in the pathological condition of outpatients with ovarian dysfunction and/or hyperprolactinemia. While a few investigators reported the extra-mammary regulation on PRL-R by PRL, our data suggest that the PRL-R levels of circulating lymphocytes could be down-regulated by the elevated serum levels of PRL and that pituitary PRL may participate in regulating the expression of PRL-R genes on cells of the human immune system, especially in physiological circumstances such as in the postpartum period.

  3. The Small GTPase Rap1b: A Bidirectional Regulator of Platelet Adhesion Receptors

    Directory of Open Access Journals (Sweden)

    Gianni Francesco Guidetti

    2012-01-01

    Full Text Available Integrins and other families of cell adhesion receptors are responsible for platelet adhesion and aggregation, which are essential steps for physiological haemostasis, as well as for the development of thrombosis. The modulation of platelet adhesive properties is the result of a complex pattern of inside-out and outside-in signaling pathways, in which the members of the Rap family of small GTPases are bidirectionally involved. This paper focuses on the regulation of the main Rap GTPase expressed in circulating platelets, Rap1b, downstream of adhesion receptors, and summarizes the most recent achievements in the investigation of the function of this protein as regulator of platelet adhesion and thrombus formation.

  4. Dopamine D2-Receptor Antagonists Down-Regulate CYP1A1/2 and CYP1B1 in the Rat Liver.

    Directory of Open Access Journals (Sweden)

    P Harkitis

    Full Text Available Dopaminergic systems regulate the release of several hormones including growth hormone (GH, thyroid hormones, insulin, glucocorticoids and prolactin (PRL that play significant roles in the regulation of various Cytochrome P450 (CYP enzymes. The present study investigated the role of dopamine D2-receptor-linked pathways in the regulation of CYP1A1, CYP1A2 and CYP1B1 that belong to a battery of genes controlled by the Aryl Hydrocarbon Receptor (AhR and play a crucial role in the metabolism and toxicity of numerous environmental toxicants. Inhibition of dopamine D2-receptors with sulpiride (SULP significantly repressed the constitutive and benzo[a]pyrene (B[a]P-induced CYP1A1, CYP1A2 and CYP1B expression in the rat liver. The expression of AhR, heat shock protein 90 (HSP90 and AhR nuclear translocator (ARNT was suppressed by SULP in B[a]P-treated livers, whereas the AhRR expression was increased by the drug suggesting that the SULP-mediated repression of the CYP1 inducibility is due to inactivation of the AhR regulatory system. At signal transduction level, the D2-mediated down-regulation of constitutive CYP1A1/2 and CYP1B1 expression appears to be mediated by activation of the insulin/PI3K/AKT pathway. PRL-linked pathways exerting a negative control on various CYPs, and inactivation of the glucocorticoid-linked pathways that positively control the AhR-regulated CYP1 genes, may also participate in the SULP-mediated repression of both, the constitutive and induced CYP1 expression. The present findings indicate that drugs acting as D2-dopamine receptor antagonists can modify several hormone systems that regulate the expression of CYP1A1, CYP1A2 and CYP1B1, and may affect the toxicity and carcinogenicity outcome of numerous toxicants and pre-carcinogenic substances. Therefore, these drugs could be considered as a part of the strategy to reduce the risk of exposure to environmental pollutants and pre-carcinogens.

  5. Melatonin receptor 1 B polymorphisms associated with the risk of gestational diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Yang Jae-Hyug

    2011-06-01

    Full Text Available Abstract Backgrounds Two SNPs in melatonin receptor 1B gene, rs10830963 and rs1387153 showed significant associations with fasting plasma glucose levels and the risk of Type 2 Diabetes Mellitus (T2DM in previous studies. Since T2DM and gestational diabetes mellitus (GDM share similar characteristics, we suspected that the two genetic polymorphisms in MTNR1B may be associated with GDM, and conducted association studies between the polymorphisms and the disease. Furthermore, we also examined genetic effects of the two polymorphisms with various diabetes-related phenotypes. Methods A total of 1,918 subjects (928 GDM patients and 990 controls were used for the study. Two MTNR1B polymorphisms were genotyped using TaqMan assay. The allele distributions of SNPs were evaluated by x2 models calculating odds ratios (ORs, 95% confidence intervals (CIs, and corresponding P values. Multiple regressions were used for association analyses of GDM-related traits. Finally, conditional analyses were also performed. Results We found significant associations between the two genetic variants and GDM, rs10830963, with a corrected P value of 0.0001, and rs1387153, with the corrected P value of 0.0008. In addition, we also found that the two SNPs were associated with various phenotypes such as homeostasis model assessment of beta-cell function and fasting glucose levels. Further conditional analyses results suggested that rs10830963 might be more likely functional in case/control analysis, although not clear in GDM-related phenotype analyses. Conclusion There have been studies that found associations between genetic variants of other genes and GDM, this is the first study that found significant associations between SNPs of MTNR1B and GDM. The genetic effects of two SNPs identified in this study would be helpful in understanding the insight of GDM and other diabetes-related disorders.

  6. The Vasopressin 1b Receptor Antagonist A-988315 Blocks Stress Effects on the Retrieval of Object-Recognition Memory

    NARCIS (Netherlands)

    Barsegyan, A.; Atsak, P.; Hornberger, W.B.; Jacobson, P.B.; Gaalen, M.M. van; Roozendaal, B.

    2015-01-01

    Stress-induced activation of the hypothalamo-pituitary-adrenocortical (HPA) axis and high circulating glucocorticoid levels are well known to impair the retrieval of memory. Vasopressin can activate the HPA axis by stimulating vasopressin 1b (V1b) receptors located on the pituitary. In the present s

  7. Antagonism of serotonin receptor 1B decreases viability and promotes apoptosis in the COS canine osteosarcoma cell line.

    Science.gov (United States)

    Viall, A K; Goodall, C P; Stang, B; Marley, K; Chappell, P E; Bracha, S

    2016-06-01

    Serotonin receptor 1B (5HTR1B) traditionally exhibits anti-proliferative activity in osteoblasts. We examined the expression and function of 5HTR1B in the COS canine osteosarcoma cell line and normal canine osteoblasts. Equal levels of 5HTR1B gene and protein expression were found between normal and malignant osteoblasts. Treatment with serotonin enhanced viability of osteosarcoma cells but not normal osteoblasts. Challenge with the 5HTR1B agonist anpirtoline caused no change in cell viability. Rather incubation with the specific receptor antagonist SB224289 caused reduction in osteoblast viability, with this effect more substantial in osteosarcoma cells. Investigation of this inhibitory activity showed 5HTR1B antagonism induces apoptosis in malignant cells. Evaluation of phosphorylated levels of CREB and ERK, transcriptional regulators associated with serotonin receptor signalling in osteoblasts, revealed aberrant 5HTR1B signalling in COS. Our results confirm the presence of 5HTR1B in a canine osteosarcoma cell line and highlight this receptor as a possible novel therapeutic target.

  8. The orphan nuclear receptor Nur77 regulates decidual prolactin expression in human endometrial stromal cells

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Yue; Hu, Yali; Zhao, Jing; Zhen, Xin [Reproductive Medicine Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008 (China); Yan, Guijun, E-mail: yanguijun33@gmail.com [Reproductive Medicine Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008 (China); Sun, Haixiang, E-mail: stevensunz@163.com [Reproductive Medicine Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008 (China)

    2011-01-14

    Research highlights: {yields} Decidually produced PRL plays a key role during pregnancy. {yields} Overexpression of Nur77 increased PRL mRNA expression and enhanced decidual PRL promoter activity. {yields} Knockdown of Nur77 decreased decidual PRL secretion induced by 8-Br-cAMP and MPA. {yields} Nur77 is a novel transcription factor that plays an active role in decidual prolactin expression. -- Abstract: Prolactin (PRL) is synthesized and released by several extrapituitary tissues, including decidualized stromal cells. Despite the important role of decidual PRL during pregnancy, little is understood about the factors involved in the proper regulation of decidual PRL expression. Here we present evidence that the transcription factor Nur77 plays an active role in decidual prolactin expression in human endometrial stromal cells (hESCs). Nur77 mRNA expression in hESCs was significantly increased after decidualization stimulated by 8-Br-cAMP and medroxyprogesterone acetate (MPA). Adenovirus-mediated overexpression of Nur77 in hESCs markedly increased PRL mRNA expression and enhanced decidual PRL promoter (dPRL/-332Luc) activity in a concentration-dependent manner. Furthermore, knockdown of Nur77 in hESCs significantly decreased decidual PRL promoter activation and substantially attenuated PRL mRNA expression and PRL secretion (P < 0.01) induced by 8-Br-cAMP and MPA. These results demonstrate that Nur77 is a novel transcription factor that contributes significantly to the regulation of prolactin gene expression in human endometrial stromal cells.

  9. Stimulation of 5-HT(1B) receptors enhances cocaine reinforcement yet reduces cocaine-seeking behavior.

    Science.gov (United States)

    Pentkowski, Nathan S; Acosta, Jazmin I; Browning, Jenny R; Hamilton, Elizabeth C; Neisewander, Janet L

    2009-09-01

    Paradoxically, stimulation of 5-HT(1B) receptors (5-HT(1B)Rs) enhances sensitivity to the reinforcing effects of cocaine but attenuates incentive motivation for cocaine as measured using the extinction/reinstatement model. We revisited this issue by examining the effects of a 5-HT(1B)R agonist, CP94253, on cocaine reinforcement and cocaine-primed reinstatement, predicting that CP94253 would enhance cocaine-seeking behavior reinstated by a low priming dose, similar to its effect on cocaine reinforcement. Rats were trained to self-administer cocaine (0.75 mg/kg, i.v.) paired with light and tone cues. For reinstatement experiments, they then underwent daily extinction training to reduce cocaine-seeking behavior (operant responses without cocaine reinforcement). Next, they were pre-treated with CP94253 (3-10 mg/kg, s.c.) and either tested for cocaine-primed (10 or 2.5 mg/kg, i.p.) or cue-elicited reinstatement of extinguished cocaine-seeking behavior. For reinforcement, effects of CP94253 (5.6 mg/kg) across a range of self-administered cocaine doses (0-1.5 mg/kg, i.v.) were examined. Cocaine dose-dependently reinstated cocaine-seeking behavior, but contrary to our prediction, CP94253 reduced reinstatement with both priming doses. Similarly, CP94253 reduced cue-elicited reinstatement. In contrast, CP94253 shifted the self-administration dose-effect curve leftward, consistent with enhanced cocaine reinforcement. When saline was substituted for cocaine, CP94253 reduced response rates (i.e. cocaine-seeking behavior). In subsequent control experiments, CP94253 decreased open-arm exploration in an elevated plus-maze suggesting an anxiogenic effect, but had no effect on locomotion or sucrose reinforcement. These results provide strong evidence that stimulation of 5-HT(1B)Rs produces opposite effects on cocaine reinforcement and cocaine-seeking behavior, and further suggest that 5-HT(1B)Rs may be a novel target for developing medications for cocaine dependence.

  10. Effects of salinity and prolactin on gene transcript levels of ion transporters, ion pumps and prolactin receptors in Mozambique tilapia intestine.

    Science.gov (United States)

    Seale, Andre P; Stagg, Jacob J; Yamaguchi, Yoko; Breves, Jason P; Soma, Satoshi; Watanabe, Soichi; Kaneko, Toyoji; Cnaani, Avner; Harpaz, Sheenan; Lerner, Darren T; Grau, E Gordon

    2014-09-15

    Euryhaline teleosts are faced with significant challenges during changes in salinity. Osmoregulatory responses to salinity changes are mediated through the neuroendocrine system which directs osmoregulatory tissues to modulate ion transport. Prolactin (PRL) plays a major role in freshwater (FW) osmoregulation by promoting ion uptake in osmoregulatory tissues, including intestine. We measured mRNA expression of ion pumps, Na(+)/K(+)-ATPase α3-subunit (NKAα3) and vacuolar type H(+)-ATPase A-subunit (V-ATPase A-subunit); ion transporters/channels, Na(+)/K(+)/2Cl(-) co-transporter (NKCC2) and cystic fibrosis transmembrane conductance regulator (CFTR); and the two PRL receptors, PRLR1 and PRLR2 in eleven intestinal segments of Mozambique tilapia (Oreochromis mossambicus) acclimated to FW or seawater (SW). Gene expression levels of NKAα3, V-ATPase A-subunit, and NKCC2 were generally lower in middle segments of the intestine, whereas CFTR mRNA was most highly expressed in anterior intestine of FW-fish. In both FW- and SW-acclimated fish, PRLR1 was most highly expressed in the terminal segment of the intestine, whereas PRLR2 was generally most highly expressed in anterior intestinal segments. While NKCC2, NKAα3 and PRLR2 mRNA expression was higher in the intestinal segments of SW-acclimated fish, CFTR mRNA expression was higher in FW-fish; PRLR1 and V-ATPase A-subunit mRNA expression was similar between FW- and SW-acclimated fish. Next, we characterized the effects of hypophysectomy (Hx) and PRL replacement on the expression of intestinal transcripts. Hypophysectomy reduced both NKCC2 and CFTR expression in particular intestinal segments; however, only NKCC2 expression was restored by PRL replacement. Together, these findings describe how both acclimation salinity and PRL impact transcript levels of effectors of ion transport in tilapia intestine.

  11. Aryl‐hydrocarbon receptor activity modulates prolactin expression in the pituitary

    Energy Technology Data Exchange (ETDEWEB)

    Moran, Tyler B.; Brannick, Katherine E.; Raetzman, Lori T., E-mail: raetzman@life.illinois.edu

    2012-11-15

    Pituitary tumors account for 15% of intracranial neoplasms, however the extent to which environmental toxicants contribute to the proliferation and hormone expression of pituitary cells is unknown. Aryl-hydrocarbon receptor (AhR) interacting protein (AIP) loss of function mutations cause somatotrope and lactotrope adenomas in humans. AIP sequesters AhR and inhibits its transcriptional function. Because of the link between AIP and pituitary tumors, we hypothesize that exposure to dioxins, potent exogenous ligands for AhR that are persistent in the environment, may predispose to pituitary dysfunction through activation of AhR. In the present study, we examined the effect of AhR activation on proliferation and endogenous pituitary hormone expression in the GH3 rat somatolactotrope tumor cell line and the effect of loss of AhR action in knockout mice. GH3 cells respond to nM doses of the reversible AhR agonist β-naphthoflavone with a robust induction of Cyp1a1. Although mRNA levels of the anti-proliferative signaling cytokine TGFbeta1 are suppressed upon β-naphthoflavone treatment, we did not observe an alteration in cell proliferation. AhR activation with β-naphthoflavone suppresses Ahr expression and impairs expression of prolactin (PRL), but not growth hormone (GH) mRNA in GH3 cells. In mice, loss of Ahr similarly leads to a reduction in Prl mRNA at P3, while Gh is unaffected. Additionally, there is a significant reduction in pituitary hormones Lhb and Fshb in the absence of Ahr. Overall, these results demonstrate that AhR is important for pituitary hormone expression and suggest that environmental dioxins can exert endocrine disrupting effects at the pituitary. -- Highlights: ► AhR signaling suppresses Prl mRNA expression. ► AhR signaling does not influence pituitary proliferation in culture. ► AhR is necessary for Prl, Lhb and Fshb expression at postnatal day 3.

  12. POLYMORPHISM OF PROLACTIN RECEPTOR GENE (PRLR IN THE POLISH LANDRACE AND POLISH LARGE WHITE SWINE POPULATION AND REPRODUCTIVE TRAITS

    Directory of Open Access Journals (Sweden)

    AGATA ZIÓŁKOWSKA

    2011-01-01

    Full Text Available Prolactin receptor gene was found in pig chromosome 16, and it is one of the genes with a significant effect on reproduction traits in sows. The objective of the research was to determine polymorphism of the prolactin receptor gene in pigs of two maternal breeds: Polish Landrace and Polish Large White, as well as analyse relations between particular allelomorphic variants, and reproduction traits of examined sows. Two PRLR gene alleles, A and B, were isolated, they were obtained after AluI restriction gene digestion of the PCR product with the length of 163 bp; furthermore, three genotypes were identified: PRLRAA – 85, 59, 19 bp; PRLRAB – 104, 85, 59, 19 bp; PRLRBB – 104, 59 bp. We assessed 122 sows, in terms of their age at the first farrowing, as well as the sizes of the two subsequent litters. No statistically significant differences were found in the examined reproduction traits in sows with different allelomorphic relations, both within each breed and between breeds. Obtained results indicate that it is necessary to conduct further research on a larger animal group.

  13. Regulation of T Cell Receptor Signaling by DENND1B in TH2 Cells and Allergic Disease.

    Science.gov (United States)

    Yang, Chiao-Wen; Hojer, Caroline D; Zhou, Meijuan; Wu, Xiumin; Wuster, Arthur; Lee, Wyne P; Yaspan, Brian L; Chan, Andrew C

    2016-01-14

    The DENN domain is an evolutionary conserved protein module found in all eukaryotes and serves as an exchange factor for Rab-GTPases to regulate diverse cellular functions. Variants in DENND1B are associated with development of childhood asthma and other immune disorders. To understand how DENND1B may contribute to human disease, Dennd1b(-/-) mice were generated and exhibit hyper-allergic responses following antigen challenge. Dennd1b(-/-) TH2, but not other TH cells, exhibit delayed receptor-induced T cell receptor (TCR) downmodulation, enhanced TCR signaling, and increased production of effector cytokines. As DENND1B interacts with AP-2 and Rab35, TH2 cells deficient in AP-2 or Rab35 also exhibit enhanced TCR-mediated effector functions. Moreover, human TH2 cells carrying asthma-associated DENND1B variants express less DENND1B and phenocopy Dennd1b(-/-) TH2 cells. These results provide a molecular basis for how DENND1B, a previously unrecognized regulator of TCR downmodulation in TH2 cells, contributes to asthma pathogenesis and how DENN-domain-containing proteins may contribute to other human disorders.

  14. Prolactin blood test

    Science.gov (United States)

    ... test; Amenorrhea - prolactin test; Breast leakage - prolactin test; Prolactinoma - prolactin test; Pituitary tumor - prolactin test ... hypothyroidism ) Kidney disease Pituitary tumor that makes prolactin (prolactinoma) Other pituitary tumors and diseases in the area ...

  15. Functional Characterization of Exonic Variants of the PPARGC1B Gene in Coregulation of Estrogen Receptor Alpha.

    Science.gov (United States)

    Chang, Hun Soo; Lee, Shin-Hwa; Lee, Jong-Uk; Park, Jong Sook; Chung, Il Yup; Park, Choon-Sik

    2016-07-01

    Peroxisome proliferator-activated receptor gamma coactivator 1 beta (PPARGC1B) is a coactivator of estrogen receptor (ER)α and ERβ. We previously demonstrated a significant association between a variant of exon 5 of the PPARGC1B gene (+102525 G>A, R265Q) and airway hyperreactivity (AHR). The aims of the study were to evaluate the genetic effects of variants of the PPARGC1B gene on the function of ERs. PPARGC1B +102525G and A gene constructs were generated using PCR and cloned into a pCMV4 promoter vector. A luciferase reporter assay was undertaken in 293T cells cotransfected with one of the PPARGC1B +102525G>A constructs, ERα, and an estrogen response element (ERE) containing a luciferase construct after treatment with 17β-estradiol. According to the luciferase reporter assay, the +102525A allele showed higher ERα activity than the +102525G allele in response to stimulation with 17β-estradiol. In addition, the interaction between ERα and PPARGC1B was evaluated by coprecipitation assay. Human influenza hemagglutinin-tagged PPARGC1B coprecipitated more intensely with ERα in the +102525A than the +102525G construct after 17β estradiol treatment. The variant +102525A allele enhances the activity of ERα to a greater degree than the +102525G allele of PPARGC1B.

  16. Variation in the coding and 3’ untranslated regions of the porcine prolactin receptor short form modifies protein expression and function

    Science.gov (United States)

    The actions of prolactin (PRL) are mediated by both long (LF) and short isoforms (SF) of the PRL receptor (PRLR). Here, we report on a genetic and functional analysis of the porcine PRLR (pPRLR) SF. Three single nucleotide polymorphisms (SNPs) within exon 11 of the pPRLR-SF give rise to four amino a...

  17. Crystal structure of an affinity-matured prolactin complexed to its dimerized receptor reveals the topology of hormone binding site 2

    DEFF Research Database (Denmark)

    Broutin, Isabelle; Jomain, Jean-Baptiste; Tallet, Estelle;

    2010-01-01

    We report the first crystal structure of a 1:2 hormone.receptor complex that involves prolactin (PRL) as the ligand, at 3.8-A resolution. Stable ternary complexes were obtained by generating affinity-matured PRL variants harboring an N-terminal tail from ovine placental lactogen, a closely relate...

  18. Normalization of hypothalamic serotonin (5-HT 1B) receptor and NPY in cancer anorexia after tumor resection: an immunocytochemical study.

    Science.gov (United States)

    Makarenko, Irina G; Meguid, Michael M; Gatto, Louis; Chen, Chung; Ramos, Eduardo J B; Goncalves, Carolina G; Ugrumov, Michael V

    2005-08-05

    Tumor growth leads to anorexia and decreased food intake, the regulation of which is via the integrated hypothalamic peptidergic and monoaminergic system. Serotonin (5-HT), an anorectic monoamine acts primarily via 5-HT 1B-receptors in hypothalamic nuclei while neuropeptide Y (NPY) acts an orexigenic peptide. We previously reported that 5-HT 1B-receptors are up regulated while NPY is down regulated in tumor-bearing (TB)-related anorexia, contributing to food intake reduction. In anorectic TB rats we hypothesize that after tumor resection when food intake has reverted to normal, normalization of 5-HT 1B-receptor and NPY will occur. The aim of this study was to demonstrate normalization of these hypothalamic changes compared to Controls. In anorectic tumor-bearing rats after tumor resection (TB-R) and in sham-operated (Control) rats, distribution of 5-HT 1B-receptors and NPY in hypothalamic nuclei was analyzed using peroxidase antiperoxidase immunocytochemical methods. Image analysis of immunostaining was performed and the data were statistically analyzed. Immunostaining specificity was controlled by omission of primary or secondary antibodies and pre-absorption test. Our results show that after TB-R versus Controls a normalization of food intake, 5-H-1B-receptor and NPY expression in the hypothalamus occurs. These data, discussed in context with our previous studies, support the hypothesis that tumor resection results not only in normalization of food intake but also in reversible changes of anorectic and orexigenic hypothalamic modulators.

  19. Serotonin/dopamine interactions in a hyperactive mouse: reduced serotonin receptor 1B activity reverses effects of dopamine transporter knockout.

    Directory of Open Access Journals (Sweden)

    Frank Scott Hall

    Full Text Available Knockout (KO mice that lack the dopamine transporter (SL6A3; DAT display increased locomotion that can be attenuated, under some circumstances, by administration of drugs that normally produce psychostimulant-like effects, such as amphetamine and methylphenidate. These results have led to suggestions that DAT KO mice may model features of attention deficit hyperactivity disorder (ADHD and that these drugs may act upon serotonin (5-HT systems to produce these unusual locomotor decreasing effects. Evidence from patterns of brain expression and initial pharmacologic studies led us to use genetic and pharmacologic approaches to examine the influence of altered 5-HT1B receptor activity on hyperactivity in DAT KO mice. Heterozygous 5-HT1B KO and pharmacologic 5-HT1B antagonism both attenuated locomotor hyperactivity in DAT KO mice. Furthermore, DAT KO mice with reduced, but not eliminated, 5-HT1B receptor expression regained cocaine-stimulated locomotion, which was absent in DAT KO mice with normal levels of 5-HT1B receptor expression. Further experiments demonstrated that the degree of habituation to the testing apparatus determined whether cocaine had no effect on locomotion in DAT KO or reduced locomotion, helping to resolve differences among prior reports. These findings of complementation of the locomotor effects of DAT KO by reducing 5-HT1B receptor activity underscore roles for interactions between specific 5-HT receptors and dopamine (DA systems in basal and cocaine-stimulated locomotion and support evaluation of 5-HT1B antagonists as potential, non-stimulant ADHD therapeutics.

  20. Lysergic acid diethylamide (LSD) is a partial agonist of D2 dopaminergic receptors and it potentiates dopamine-mediated prolactin secretion in lactotrophs in vitro.

    Science.gov (United States)

    Giacomelli, S; Palmery, M; Romanelli, L; Cheng, C Y; Silvestrini, B

    1998-01-01

    The hallucinogenic effects of lysergic acid diethylamide (LSD) have mainly been attributed to the interaction of this drug with the serotoninergic system, but it seems more likely that they are the result of the complex interactions of the drug with both the serotoninergic and dopaminergic systems. The aim of the present study was to investigate the functional actions of LSD at dopaminergic receptors using prolactin secretion by primary cultures of rat pituitary cells as a model. LSD produced a dose-dependent inhibition of prolactin secretion in vitro with an IC50 at 1.7x10(-9) M. This action was antagonized by spiperone but not by SKF83566 or cyproheptadine, which indicates that LSD has a specific effect on D2 dopaminergic receptors. The maximum inhibition of prolactin secretion achieved by LSD was lower than that by dopamine (60% versus 80%). Moreover, the fact that LSD at 10(-8)-10(-6) M antagonized the inhibitory effect of dopamine (10(-7) M) and bromocriptine (10(-11) M) suggests that LSD acts as a partial agonist at D2 receptors on lactotrophs in vitro. Interestingly, LSD at 10(-13)-10(-10) M, the concentrations which are 10-1000-fold lower than those required to induce direct inhibition on pituitary prolactin secretion, potentiated the dopamine (10(-10)-2.5x10(-9) M)-mediated prolactin secretion by pituitary cells in vitro. These results suggest that LSD not only interacts with dopaminergic receptors but also has a unique capacity for modulating dopaminergic transmission. These findings may offer new insights into the hallucinogenic effect of LSD.

  1. Prolactin Rescues Immature B-Cells from Apoptosis Induced by B-Cell Receptor Cross-Linking.

    Science.gov (United States)

    Flores-Fernández, Rocio; Blanco-Favela, Francisco; Fuentes-Pananá, Ezequiel M; Chávez-Sánchez, Luis; Gorocica-Rosete, Patricia; Pizaña-Venegas, Alberto; Chávez-Rueda, Adriana Karina

    2016-01-01

    Prolactin has an immunomodulatory effect and has been associated with B-cell-triggered autoimmune diseases, such as systemic lupus erythematosus (SLE). In mice that develop SLE, the PRL receptor is expressed in early bone marrow B-cells, and increased levels of PRL hasten disease manifestations, which are correlated with a reduction in the absolute number of immature B-cells. The aim of this work was to determine the effect of PRL in an in vitro system of B-cell tolerance using WEHI-231 cells and immature B-cells from lupus prone MRL/lpr mice. WEHI-231 cells express the long isoform of the PRL receptor, and PRL rescued the cells from cell death by decreasing the apoptosis induced by the cross-linking of the B-cell antigen receptor (BCR) as measured by Annexin V and active caspase-3. This decrease in apoptosis may have been due to the PRL and receptor interaction, which increased the relative expression of antiapoptotic Bcl-xL and decreased the relative expression of proapoptotic Bad. In immature B-cells from MRL/lpr mice, PRL increased the viability and decreased the apoptosis induced by the cross-linking of BCR, which may favor the maturation of self-reactive B-cells and contribute to the onset of disease.

  2. Prolactin Rescues Immature B-Cells from Apoptosis Induced by B-Cell Receptor Cross-Linking

    Directory of Open Access Journals (Sweden)

    Rocio Flores-Fernández

    2016-01-01

    Full Text Available Prolactin has an immunomodulatory effect and has been associated with B-cell-triggered autoimmune diseases, such as systemic lupus erythematosus (SLE. In mice that develop SLE, the PRL receptor is expressed in early bone marrow B-cells, and increased levels of PRL hasten disease manifestations, which are correlated with a reduction in the absolute number of immature B-cells. The aim of this work was to determine the effect of PRL in an in vitro system of B-cell tolerance using WEHI-231 cells and immature B-cells from lupus prone MRL/lpr mice. WEHI-231 cells express the long isoform of the PRL receptor, and PRL rescued the cells from cell death by decreasing the apoptosis induced by the cross-linking of the B-cell antigen receptor (BCR as measured by Annexin V and active caspase-3. This decrease in apoptosis may have been due to the PRL and receptor interaction, which increased the relative expression of antiapoptotic Bcl-xL and decreased the relative expression of proapoptotic Bad. In immature B-cells from MRL/lpr mice, PRL increased the viability and decreased the apoptosis induced by the cross-linking of BCR, which may favor the maturation of self-reactive B-cells and contribute to the onset of disease.

  3. Prolactin Rescues Immature B-Cells from Apoptosis Induced by B-Cell Receptor Cross-Linking

    Science.gov (United States)

    Flores-Fernández, Rocio; Blanco-Favela, Francisco; Fuentes-Pananá, Ezequiel M.; Chávez-Sánchez, Luis; Gorocica-Rosete, Patricia; Pizaña-Venegas, Alberto; Chávez-Rueda, Adriana Karina

    2016-01-01

    Prolactin has an immunomodulatory effect and has been associated with B-cell-triggered autoimmune diseases, such as systemic lupus erythematosus (SLE). In mice that develop SLE, the PRL receptor is expressed in early bone marrow B-cells, and increased levels of PRL hasten disease manifestations, which are correlated with a reduction in the absolute number of immature B-cells. The aim of this work was to determine the effect of PRL in an in vitro system of B-cell tolerance using WEHI-231 cells and immature B-cells from lupus prone MRL/lpr mice. WEHI-231 cells express the long isoform of the PRL receptor, and PRL rescued the cells from cell death by decreasing the apoptosis induced by the cross-linking of the B-cell antigen receptor (BCR) as measured by Annexin V and active caspase-3. This decrease in apoptosis may have been due to the PRL and receptor interaction, which increased the relative expression of antiapoptotic Bcl-xL and decreased the relative expression of proapoptotic Bad. In immature B-cells from MRL/lpr mice, PRL increased the viability and decreased the apoptosis induced by the cross-linking of BCR, which may favor the maturation of self-reactive B-cells and contribute to the onset of disease. PMID:27314053

  4. Ectodomains of the LDL receptor-related proteins LRP1b and LRP4 have anchorage independent functions in vivo.

    Directory of Open Access Journals (Sweden)

    Martin F Dietrich

    Full Text Available BACKGROUND: The low-density lipoprotein (LDL receptor gene family is a highly conserved group of membrane receptors with diverse functions in developmental processes, lipoprotein trafficking, and cell signaling. The low-density lipoprotein (LDL receptor-related protein 1b (LRP1B was reported to be deleted in several types of human malignancies, including non-small cell lung cancer. Our group has previously reported that a distal extracellular truncation of murine Lrp1b that is predicted to secrete the entire intact extracellular domain (ECD is fully viable with no apparent phenotype. METHODS AND PRINCIPAL FINDINGS: Here, we have used a gene targeting approach to create two mouse lines carrying internally rearranged exons of Lrp1b that are predicted to truncate the protein closer to the N-terminus and to prevent normal trafficking through the secretary pathway. Both mutations result in early embryonic lethality, but, as expected from the restricted expression pattern of LRP1b in vivo, loss of Lrp1b does not cause cellular lethality as homozygous Lrp1b-deficient blastocysts can be propagated normally in culture. This is similar to findings for another LDL receptor family member, Lrp4. We provide in vitro evidence that Lrp4 undergoes regulated intramembraneous processing through metalloproteases and gamma-secretase cleavage. We further demonstrate negative regulation of the Wnt signaling pathway by the soluble extracellular domain. CONCLUSIONS AND SIGNIFICANCE: Our results underline a crucial role for Lrp1b in development. The expression in mice of truncated alleles of Lrp1b and Lrp4 with deletions of the transmembrane and intracellular domains leads to release of the extracellular domain into the extracellular space, which is sufficient to confer viability. In contrast, null mutations are embryonically (Lrp1b or perinatally (Lrp4 lethal. These findings suggest that the extracellular domains of both proteins may function as a scavenger for

  5. Secondhand cigarette smoke exposure causes upregulation of cerebrovascular 5-HT(1) (B) receptors via the Raf/ERK/MAPK pathway in rats

    DEFF Research Database (Denmark)

    Cao, L; Xu, C B; Zhang, Y;

    2013-01-01

    Cigarette smoke exposure increases the risk of stroke. Upregulation of 5-hydroxytryptamine 1B (5-HT(1) (B) ) receptors is associated with the pathogenesis of cerebral ischaemia. This study examined the hypothesis that the expression of 5-HT(1) (B) receptors is altered in brain vessels after...

  6. Protein-tyrosine phosphatase 1B (PTP1B) is a novel regulator of central brain-derived neurotrophic factor and tropomyosin receptor kinase B (TrkB) signaling.

    Science.gov (United States)

    Ozek, Ceren; Kanoski, Scott E; Zhang, Zhong-Yin; Grill, Harvey J; Bence, Kendra K

    2014-11-14

    Neuronal protein-tyrosine phosphatase 1B (PTP1B) deficiency in mice results in enhanced leptin signaling and protection from diet-induced obesity; however, whether additional signaling pathways in the brain contribute to the metabolic effects of PTP1B deficiency remains unclear. Here, we show that the tropomyosin receptor kinase B (TrkB) receptor is a direct PTP1B substrate and implicate PTP1B in the regulation of the central brain-derived neurotrophic factor (BDNF) signaling. PTP1B interacts with activated TrkB receptor in mouse brain and human SH-SY5Y neuroblastoma cells. PTP1B overexpression reduces TrkB phosphorylation and activation of downstream signaling pathways, whereas PTP1B inhibition augments TrkB signaling. Notably, brains of Ptpn1(-/-) mice exhibit enhanced TrkB phosphorylation, and Ptpn1(-/-) mice are hypersensitive to central BDNF-induced increase in core temperature. Taken together, our findings demonstrate that PTP1B is a novel physiological regulator of TrkB and that enhanced BDNF/TrkB signaling may contribute to the beneficial metabolic effects of PTP1B deficiency.

  7. Reduced 5-HT(1B) receptor binding in the dorsal brain stem after cognitive behavioural therapy of major depressive disorder.

    Science.gov (United States)

    Tiger, Mikael; Rück, Christian; Forsberg, Anton; Varrone, Andrea; Lindefors, Nils; Halldin, Christer; Farde, Lars; Lundberg, Johan

    2014-08-30

    Major depression is a significant contributor to the global burden of disease, and its pathophysiology is largely unknown. The serotonin hypothesis is, however, the model with most supporting data, although the details are only worked out to some extent. Recent clinical imaging measurements indeed imply a role in major depressive disorder (MDD) for the inhibitory serotonin autoreceptor 5-hydroxytryptamine1B (5-HT1B). The aim of the current study was to examine 5-HT1B receptor binding in the brain of MDD patients before and after psychotherapy. Ten patients with an ongoing untreated moderate depressive episode were examined with positron emission tomography (PET) and the 5-HT1B receptor selective radioligand [(11)C]AZ10419369, before and after treatment with internet-based cognitive behavioural therapy. All of the patients examined responded to treatment, and 70% were in remission by the time of the second PET measurement. A statistically significant 33% reduction of binding potential (BPND) was found in the dorsal brain stem (DBS) after treatment. No other significant changes in BPND were found. The DBS contains the raphe nuclei, which regulate the serotonin system. This study gives support for the importance of serotonin and the 5-HT1B receptor in the biological response to psychological treatment of MDD.

  8. The effect of chronic selective serotonin reuptake inhibitor treatment on serotonin(1B) receptor sensitivity and HPA axis activity

    NARCIS (Netherlands)

    Jongsma, M.E.; Bosker, F.J; Cremers, T.I.F.H.; Westerink, B.H.C.; Den Boer, J.A.

    2005-01-01

    The authors have investigated 5-HT1B receptor function in prefrontal cortex and dorsal hippocampus as well as the HPA axis response after subchronic (24 h) and chronic (15 days) treatment with the SSRI citalopram. All experiments were carried out in presence of citalopram to prevent rapid resensitiz

  9. Partial agonist properties of the antipsychotics SSR181507, aripiprazole and bifeprunox at dopamine D2 receptors: G protein activation and prolactin release.

    Science.gov (United States)

    Cosi, Cristina; Carilla-Durand, Elisabeth; Assié, Marie Bernadette; Ormiere, Anne Marie; Maraval, Mireille; Leduc, Nathalie; Newman-Tancredi, Adrian

    2006-03-27

    Dopamine D2 receptor antagonists induce hyperprolactinemia depending on the extent of D2 receptor blockade. We compared the effects of the new antipsychotic agents SSR181507 ((3-exo)-8-benzoyl-N-[[(2 s)7-chloro-2,3-dihydro-1,4-benzodioxin-1-yl]methyl]-8-azabicyclo[3.2.1]octane-3-methanamine monohydrochloride), bifeprunox (DU127090: 1-(2-Oxo-benzoxazolin-7-yl)-4-(3-biphenyl)methylpiperazinemesylate) and SLV313 (1-(2,3-dihydro-benzo[1,4]dioxin-5-yl)-4-[5-(4-fluorophenyl)-pyridin-3-ylmethyl]-piperazine) with those of aripiprazole (7-{4-[4-(2,3-dichlorophenyl)-1-piperazinyl]-butyloxy)-3,4-dihydro-2(1 H)-quinolinone), clozapine and haloperidol, on functional measures of dopamine D2 receptor activity in vitro and in vivo: [35S]-GTPgammaS binding to membranes from Sf9 insect cells expressing human dopamine D2 Long (hD2 L) receptors, and serum prolactin levels in the rat. All compounds antagonized apomorphine-induced G protein activation at dopamine hD2 L receptors. Antagonist potencies of aripiprazole, bifeprunox and SLV313 were similar to haloperidol (pK(b) = 9.12), whereas SSR181507 (8.16) and clozapine (7.35) were less potent. Haloperidol, SLV313 and clozapine were silent antagonists but SSR181507, bifeprunox and aripiprazole stimulated [35S]-GTPgammaS binding by 17.5%, 26.3% and 25.6%, respectively, relative to 100 microM apomorphine (Emax = 100%). pEC50s were: SSR181507, 8.08; bifeprunox, 8.97; aripiprazole, 8.56. These effects were antagonized by raclopride. Following oral administration in vivo, the drugs increased prolactin release to different extents. SLV313 and haloperidol potently (ED50 0.12 and 0.22 mg/kg p.o., respectively) stimulated prolactin release up to 86 and 83 ng/ml. Aripiprazole potently (ED50 0.66 mg/kg p.o.) but partially (32 ng/ml) induced prolactin release. SSR181507 (ED50 4.9 mg/kg p.o.) also partially (23 ng/ml) enhanced prolactin release. Bifeprunox only weakly increased prolactin at high doses (13 ng/ml at 40 mg/kg) and clozapine only

  10. Fetal Alcohol Exposure Reduces Dopamine Receptor D2 and Increases Pituitary Weight and Prolactin Production via Epigenetic Mechanisms.

    Directory of Open Access Journals (Sweden)

    Omkaram Gangisetty

    Full Text Available Recent evidence indicated that alcohol exposure during the fetal period increases the susceptibility to tumor development in mammary and prostate tissues. Whether fetal alcohol exposure increases the susceptibility to prolactin-producing tumor (prolactinoma development in the pituitary was studied by employing the animal model of estradiol-induced prolactinomas in Fischer 344 female rats. We employed an animal model of fetal alcohol exposure that simulates binge alcohol drinking during the first two trimesters of human pregnancy and involves feeding pregnant rats with a liquid diet containing 6.7% alcohol during gestational day 7 to day 21. Control rats were pair-fed with isocaloric liquid diet or fed ad libitum with rat chow diet. Adult alcohol exposed and control female offspring rats were used in this study on the day of estrus or after estrogen treatment. Results show that fetal alcohol-exposed rats had increased levels of pituitary weight, pituitary prolactin (PRL protein and mRNA, and plasma PRL. However, these rats show decreased pituitary levels of dopamine D2 receptor (D2R mRNA and protein and increased pituitary levels of D2R promoter methylation. Also, they show elevated pituitary mRNA levels of DNA methylating genes (DNMT1, DNMT3b, MeCP2 and histone modifying genes (HDAC2, HDAC4, G9a. When fetal alcohol exposed rats were treated neonatally with a DNA methylation inhibitor 5-Aza deoxycytidine and/or a HDAC inhibitor trichostatin-A their pituitary D2R mRNA, pituitary weights and plasma PRL levels were normalized. These data suggest that fetal alcohol exposure programs the pituitary to increase the susceptibility to the development of prolactinomas possibly by enhancing the methylation of the D2R gene promoter and repressing the synthesis and control of D2R on PRL-producing cells.

  11. Activation of GABA B receptors in the anterior pituitary inhibits prolactin and luteinizing hormone secretion.

    Science.gov (United States)

    Lux-Lantos, V; Rey, E; Libertun, C

    1992-11-01

    Previous work from our laboratory showed that baclofen could lower serum prolactin (PRL) levels acting at the central nervous system. The present experiments were designed to evaluate whether the gamma-aminobutyric acid B agonist was also effective in inhibiting hormone release at the pituitary level. In monolayer cultures of adenohypophyseal dispersed cells, baclofen inhibited basal PRL secretion after 1 or 2 h of incubation. This inhibition was significantly abolished by three antagonists: phaclofen, 3-aminopropyl-phosphonic acid and 4-aminobutylphosphonic acid. Furthermore, baclofen inhibited the thyrotropin-releasing hormone-induced PRL release in a concentration-dependent manner. With regard to gonadotropin secretion, baclofen was unable to modify basal luteinizing hormone (LH) secretion, but significantly inhibited the LH-releasing hormone-induced LH release. These results show that baclofen, in addition to its central neuroendocrine effects, inhibits pituitary hormone secretion, under basal and/or stimulated conditions, by direct action at the pituitary level.

  12. Regional variation in aortic AT1b receptor mRNA abundance is associated with contractility but unrelated to atherosclerosis and aortic aneurysms.

    Directory of Open Access Journals (Sweden)

    Aruna Poduri

    Full Text Available BACKGROUND: Angiotensin II (AngII, the main bioactive peptide of the renin angiotensin system, exerts most of its biological actions through stimulation of AngII type 1 (AT1 receptors. This receptor is expressed as 2 structurally similar subtypes in rodents, termed AT1a and AT1b. Although AT1a receptors have been studied comprehensively, roles of AT1b receptors in the aorta have not been defined. METHODOLOGY/RESULTS: We initially compared the regional distribution of AT1b receptor mRNA with AT1a receptor mRNA in the aorta. mRNA abundance of both subtypes increased from the proximal to the distal aorta, with the greatest abundance in the infra-renal region. Corresponding to the high mRNA abundance for both receptors, only aortic rings from the infra-renal aorta contracted in response to AngII stimulation. Despite the presence of both receptor transcripts, deletion of AT1b receptors, but not AT1a receptors, diminished AngII-induced contractility. To determine whether absence of AT1b receptors influenced aortic pathologies, we bred AT1b receptor deficient mice into an LDL receptor deficient background. Mice were fed a diet enriched in saturated fat and infused with AngII (1,000 ng/kg/min. Parameters that could influence development of aortic pathologies, including systolic blood pressure and plasma cholesterol concentrations, were not impacted by AT1b receptor deficiency. Absence of AT1b receptors also had no effect on size of aortic atherosclerotic lesions and aortic aneurysms in both the ascending and abdominal regions. CONCLUSIONS/SIGNIFICANCE: Regional abundance of AT1b receptor mRNA coincided with AngII-induced regional contractility, but it was not associated with AngII-induced aortic pathologies.

  13. New insights in prolactin: pathological implications.

    Science.gov (United States)

    Bernard, Valérie; Young, Jacques; Chanson, Philippe; Binart, Nadine

    2015-05-01

    Prolactin is a hormone that is mainly secreted by lactotroph cells of the anterior pituitary gland, and is involved in many biological processes including lactation and reproduction. Animal models have provided insights into the biology of prolactin proteins and offer compelling evidence that the different prolactin isoforms each have independent biological functions. The major isoform, 23 kDa prolactin, acts via its membrane receptor, the prolactin receptor (PRL-R), which is a member of the haematopoietic cytokine superfamily and for which the mechanism of activation has been deciphered. The 16 kDa prolactin isoform is a cleavage product derived from native prolactin, which has received particular attention as a result of its newly described inhibitory effects on angiogenesis and tumorigenesis. The discovery of multiple extrapituitary sites of prolactin secretion also increases the range of known functions of this hormone. This Review summarizes current knowledge of the biology of prolactin and its receptor, as well as its physiological and pathological roles. We focus on the role of prolactin in human pathophysiology, particularly the discovery of the mechanism underlying infertility associated with hyperprolactinaemia and the identification of the first mutation in human PRLR.

  14. Two Independent Histidines One in Human Prolactin and One in Its Receptor Are Critical for pH-dependent Receptor Recognition and Activation

    Energy Technology Data Exchange (ETDEWEB)

    M Kulkarni; M Tettamanzi; J Murphy; C Keeler; D Myszka; N Chayen; E Lolis; M Hodsdon

    2011-12-31

    Human prolactin (hPRL), a member of the family of hematopoietic cytokines, functions as both an endocrine hormone and autocrine/paracrine growth factor. We have previously demonstrated that recognition of the hPRL-receptor depends strongly on solution acidity over the physiologic range from pH 6 to pH 8. The hPRL-receptor binding interface contains four histidines whose protonation is hypothesized to regulate pH-dependent receptor recognition. Here, we systematically dissect its molecular origin by characterizing the consequences of His to Ala mutations on pH-dependent receptor binding kinetics, site-specific histidine protonation, and high resolution structures of the intermolecular interface. Thermodynamic modeling of the pH dependence to receptor binding affinity reveals large changes in site-specific protonation constants for a majority of interface histidines upon complexation. Removal of individual His imidazoles reduces these perturbations in protonation constants, which is most likely explained by the introduction of solvent-filled, buried cavities in the crystallographic structures without inducing significant conformational rearrangements.

  15. Gi-protein-coupled 5-HT1B/D receptor agonist sumatriptan induces type I hyperalgesic priming.

    Science.gov (United States)

    Araldi, Dioneia; Ferrari, Luiz F; Levine, Jon D

    2016-08-01

    We have recently described a novel form of hyperalgesic priming (type II) induced by agonists at two clinically important Gi-protein-coupled receptors (Gi-GPCRs), mu-opioid and A1-adenosine. Like mu-opioids, the antimigraine triptans, which act at 5-HT1B/D Gi-GPCRs, have been implicated in pain chronification. We determined whether sumatriptan, a prototypical 5-HT1B/D agonist, produces type II priming. Characteristic of hyperalgesic priming, intradermal injection of sumatriptan (10 ng) induced a change in nociceptor function such that a subsequent injection of prostaglandin-E2 (PGE2) induces prolonged mechanical hyperalgesia. However, onset to priming was delayed 3 days, characteristic of type I priming. Also characteristic of type I priming, a protein kinase Cε, but not a protein kinase A inhibitor attenuated the prolongation phase of PGE2 hyperalgesia. The prolongation of PGE2 hyperalgesia was also permanently reversed by intradermal injection of cordycepin, a protein translation inhibitor. Also, hyperalgesic priming did not occur in animals pretreated with pertussis toxin or isolectin B4-positive nociceptor toxin, IB4-saporin. Finally, as observed for other agonists that induce type I priming, sumatriptan did not induce priming in female rats. The prolongation of PGE2 hyperalgesia induced by sumatriptan was partially prevented by coinjection of antagonists for the 5-HT1B and 5-HT1D, but not 5-HT7, serotonin receptors and completely prevented by coadministration of a combination of the 5-HT1B and 5-HT1D antagonists. Moreover, the injection of selective agonists, for 5-HT1B and 5-HT1D receptors, also induced hyperalgesic priming. Our results suggest that sumatriptan, which signals through Gi-GPCRs, induces type I hyperalgesic priming, unlike agonists at other Gi-GPCRs, which induce type II priming.

  16. Effect of Prolactin Receptor (PRLR) and Beta-Casein (CSN2) Gene Polymorphism on the Chemical Composition of Milk Sows.

    Science.gov (United States)

    Skrzypczak, Ewa; Babicz, Marek; Pastwa, Marcin

    2015-01-01

    The objective of the studies was to evaluate the impact of the prolactin receptor and β-casein genes on the basic chemical composition and pH of the colostrum and milk of sows. Experiments were carried out on 103 Złotnicka White breed sows. These animals are under the Domestic Program of Protection of Genetic Resources. Analysis of the influence of polymorphism in the PRLR and CSN2 loci revealed that sows of the TT homozygote were characterised by the highest dry matter content. Analysis of polymorphism in the PRLR locus for protein showed that the highest values were in milk of sows of the TT genotype, and GG homozygotes in the case of the CSN2 locus. Inference of the impact of polymorphism in the PRLR and CSN2 loci on the fat and lactose content of sow milk demonstrated considerable variability. These differences were statistically significant at the level of α = 0.01 and α = 0.05. Periodical changes in individual pH values were apparent for particular genotypes in both loci (PRLR and CSN2). The perceptible changes that occurred between individual genotypes were statistically significant at the levels of α = 0.01 and α = 0.05. The investigations confirmed that the nutritive values of sow colostrum and milk were determined by genetic factors. This issue warrants comprehensive analysis, especially in terms of evaluation of the breeding value of maternal breeds.

  17. Polymorphisms in the melatonin receptor 1B gene and the risk of delirium

    NARCIS (Netherlands)

    de Jonghe, A; de Rooij, S; Tanck, M W T; Sijbrands, E J G; van Munster, B C V

    2012-01-01

    BACKGROUND/AIMS: A disturbed sleep-wake rhythm cycle can be seen in delirium and as melatonin regulates this cycle via melatonin receptors, genetic variations in these receptors may contribute to susceptibility to delirium. The purpose of this study was to investigate whether genetic variants in the

  18. Prolactin and cancer: Has the orphan finally found a home?

    Directory of Open Access Journals (Sweden)

    Bipin Kumar Sethi

    2012-01-01

    Full Text Available Prolactin has, for long, been associated with galactorrhea and infertility in women while its role in men is largely unknown. Recently, expression of prolactin in various other tissues like the breast, prostate, decidua, and the brain has been recognized. This has led to evaluation of paracrine and autocrine actions of prolactin at these tissues and a possible role in development of various cancers. Increased expression of PRL receptors has also been implicated in carcinogenesis. Breast cancer has the strongest association with increased prolactin and prolactin receptor levels. Prostate cancer also has reported significant association, while the role of prolactin in colorectal, gynecological, laryngeal, and hepatocellular cancers is more tenuous. Prolactin/prolactin receptor pathway has also been implicated in development of resistance to chemotherapy. Thus, the effects of this pathway in carcinogenesis seem widespread. At the same time, they also offer an exciting new approach to hormonal manipulation of cancers, especially the treatment-resistant cancers.

  19. Effects of cannabinoid receptor 1 (brain) on lipid accumulation by transcriptional control of CPT1A and CPT1B.

    Science.gov (United States)

    Zhang, Y-F; Yuan, Z-Q; Song, D-G; Zhou, X-H; Wang, Y-Z

    2014-02-01

    CB1 (also known as CNR1), a main receptor for cannabinoids acting at PPARs, can enhance fat deposition. Carnitine palmitoyltransferase-1 (CPT1), an enzyme responsible for the transport of long-chain fatty acids for β-oxidation, is closely related to fat deposition. Whether CB1 can regulate intramuscular adipocytes lipid accumulation through regulation of CPT1 is unclear. Based on the investigation of tissue- and breed-specific CPT1A and CPT1B mRNA expression levels in Jinhua and Landrace pigs, we studied the effects of CB1 on lipid accumulation and CPT1B expression by treating porcine intramuscular adipocytes with CB1 antagonist Δ9-THC and antagonist SR141716. Results showed that muscle CPT1 mRNA was expressed at higher levels in the longissimus dorsi and subcutaneous fat. Liver CPT1A mRNA expression levels were higher in the pancreas, duodenum and liver. Compared with Landrace pigs, CPT1A and CPT1B in the longissimus dorsi of Jinhua pigs were significantly higher and positively correlated with intramuscular fat content. However, for subcutaneous fat, CPT1 levels were significantly lower and negatively correlated with body fat percentage. Δ9-THC significantly increased CB1 mRNA levels and lipid accumulation but decreased CPT1A and CPT1B mRNA levels. Conversely, SR141716 reduced CB1 mRNA levels but increased CPT1A and CPT1B mRNA levels, resulting in decreased lipid accumulation. The CPT1 antagonist etomoxir did not affect CB1 expression, suggesting that CB1 is likely upstream of CPT1A and CPT1B. Meanwhile, PPARA expression was greatly decreased when CPT1A and CPT1B were inhibited and enhanced when CPT1A and CPT1B were activated. Taken together, these data indicate that CB1 can affect intramuscular fat deposition by regulating both CPT1A and CPT1B mRNA expression, with the PPARA signal pathway likely playing a major role in this process.

  20. 5-HT1B receptor modulation of the serotonin transporter in vivo: Studies using KO mice

    OpenAIRE

    Montañez, Sylvia; Munn, Jaclyn L.; Owens, W. Anthony; Horton, Rebecca E.; Daws, Lynette C.

    2013-01-01

    The serotonin transporter (SERT) controls the strength and duration of serotonergic neurotransmission by the high-affinity uptake of ser otonin (5-HT) from extracellular fluid. SERT is a key target for many psychotherapeutic and abused drugs, therefore understanding how SERT activity and expression are regulated is of fundamental importance. A growing literature suggests that SERT activity is under regulatory control of the 5-HT1B autoreceptor. The present studies made use of mice with a cons...

  1. Interaction between Serotonin Transporter and Serotonin Receptor 1 B genes polymorphisms may be associated with antisocial alcoholism

    Directory of Open Access Journals (Sweden)

    Wang Tzu-Yun

    2012-07-01

    Full Text Available Abstract Background Several studies have hypothesized that genes regulating the components of the serotonin system, including serotonin transporter (5-HTTLPR and serotonin 1 B receptor (5-HT1B, may be associated with alcoholism, but their results are contradictory because of alcoholism’s heterogeneity. Therefore, we examined whether the 5-HTTLPR gene and 5-HT1B gene G861C polymorphism are susceptibility factors for a specific subtype of alcoholism, antisocial alcoholism in Han Chinese in Taiwan. Methods We recruited 273 Han Chinese male inmates with antisocial personality disorder (ASPD [antisocial alcoholism (AS-ALC group (n = 120 and antisocial non-alcoholism (AS-N-ALC group (n = 153] and 191 healthy male controls from the community. Genotyping was done using PCR-RFLP. Results There were no significant differences in the genotypic frequency of the 5-HT1B G861C polymorphism between the 3 groups. Although AS-ALC group members more frequently carried the 5-HTTLPR S/S, S/LG, and LG/LG genotypes than controls, the difference became non-significant after controlling for the covarying effects of age. However, the 5-HTTLPR S/S, S/LG, and LG/LG genotypes may have interacted with the 5-HT1B G861C C/C polymorphism and increased the risk of becoming antisocial alcoholism. Conclusion Our study suggests that neither the 5-HTTLPR gene nor the 5-HT1B G861C polymorphism alone is a risk factor for antisocial alcoholism in Taiwan’s Han Chinese population, but that the interaction between both genes may increase susceptibility to antisocial alcoholism.

  2. The effect of genetic variation of the serotonin 1B receptor gene on impulsive aggressive behavior and suicide.

    Science.gov (United States)

    Zouk, Hana; McGirr, Alexander; Lebel, Véronique; Benkelfat, Chawky; Rouleau, Guy; Turecki, Gustavo

    2007-12-05

    Impulsive-aggressive behaviors (IABs) are regarded as possible suicide intermediate phenotypes, mediating the relationship between genes and suicide outcome. In this study, we aimed to investigate the putative relationship between genetic variation at the 5-HT1B receptor gene, which in animal models is involved in impulse-aggression control, IABs, and suicide risk. We investigated the relationship of variation at five 5-HT1B loci and IAB measures in a sample of 696 subjects, including 338 individuals who died by suicide and 358 normal epidemiological controls. We found that variation at the 5-HT1B promoter A-161T locus had a significant effect on levels of IABs, as measured by the Buss-Durkee Hostility Inventory (BDHI). Suicides also differed from controls in distribution of variants at this locus. The A-161T locus, which seems to impact 5-HT1B transcription, could play a role in suicide predisposition by means of mediating impulsive-aggressive behaviors.

  3. Effects on prolactin secretion and binding to dopaminergic receptors in sleep-deprived lupus-prone mice

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    B.D. Palma

    2009-03-01

    Full Text Available Sleep disturbances have far-reaching effects on the neuroendocrine and immune systems and may be linked to disease manifestation. Sleep deprivation can accelerate the onset of lupus in NZB/NZWF1 mice, an animal model of severe systemic lupus erythematosus. High prolactin (PRL concentrations are involved in the pathogenesis of systemic lupus erythematosus in human beings, as well as in NZB/NZWF1 mice. We hypothesized that PRL could be involved in the earlier onset of the disease in sleep-deprived NZB/NZWF1 mice. We also investigated its binding to dopaminergic receptors, since PRL secretion is mainly controlled by dopamine. Female NZB/NZWF1 mice aged 9 weeks were deprived of sleep using the multiple platform method. Blood samples were taken for the determination of PRL concentrations and quantitative receptor autoradiography was used to map binding of the tritiated dopaminergic receptor ligands [³H]-SCH23390, [³H]-raclopride and [³H]-WIN35,428 to D1 and D2 dopaminergic receptors and dopamine transporter sites throughout the brain, respectively. Sleep deprivation induced a significant decrease in plasma PRL secretion (2.58 ± 0.95 ng/mL compared with the control group (25.25 ± 9.18 ng/mL. The binding to D1 and D2 binding sites was not significantly affected by sleep deprivation; however, dopamine transporter binding was significantly increased in subdivisions of the caudate-putamen - posterior (16.52 ± 0.5 vs 14.44 ± 0.6, dorsolateral (18.84 ± 0.7 vs 15.97 ± 0.7 and ventrolateral (24.99 ± 0.5 vs 22.54 ± 0.7 µCi/g, in the sleep-deprived mice when compared to the control group. These results suggest that PRL is not the main mechanism involved in the earlier onset of the disease observed in sleep-deprived NZB/NZWF1 mice and the reduction of PRL concentrations after sleep deprivation may be mediated by modifications in the dopamine transporter sites of the caudate-putamen.

  4. Role of prolactin in B cell regulation in multiple sclerosis.

    Science.gov (United States)

    Correale, Jorge; Farez, Mauricio F; Ysrraelit, María Célica

    2014-04-15

    The role of prolactin in MS pathogenesis was investigated. Prolactin levels were higher in MS subjects both during remission and exacerbation compared to control subjects. Prolactin increased JAK2 expression and Stat phosphorylation on B cells, up-regulated anti-MOG antibody secreting cell numbers, BAFF levels, and Bcl-2expression, and down-regulated expression of Trp63. Prolactin levels correlated positively with anti-MOG secreting cell numbers, and negatively with induced apoptotic B cells. Additionally, prolactin decreased B cell receptor-mediated activation threshold, and induced CD40 expression in B cells. These findings suggest that prolactin promotes B cell autoreactivity in MS through different mechanisms.

  5. ASD and Genetic Associations with Receptors for Oxytocin and Vasopressin—AVPR1A, AVPR1B, and OXTR

    Science.gov (United States)

    Francis, Sunday M.; Kim, Soo-Jeong; Kistner-Griffin, Emily; Guter, Stephen; Cook, Edwin H.; Jacob, Suma

    2016-01-01

    Background: There are limited treatments available for autism spectrum disorder (ASD). Studies have reported significant associations between the receptor genes of oxytocin (OT) and vasopressin (AVP) and ASD diagnosis, as well as ASD-related phenotypes. Researchers have also found the manipulation of these systems affects social and repetitive behaviors, core characteristics of ASD. Consequently, research involving the oxytocin/vasopressin pathways as intervention targets has increased. Therefore, further examination into the relationship between these neuropeptides and ASD was undertaken. In this study, we examined associations between variants in the receptor genes of vasopressin (AVPR1A, AVPR1B), oxytocin (OXTR), and ASD diagnosis along with related subphenotypes. Methods: Probands were assessed using Autism Diagnostic Interview-Revised, Autism Diagnostic Observation Schedule, and clinical DSM-IV-TR criteria. Single nucleotide polymorphisms (SNPs) in AVPR1B and OXTR, and microsatellites in AVPR1A were genotyped in ~200 families with a proband with ASD. Family-based association testing (FBAT) was utilized to determine associations between variants and ASD. Haplotypes composed of OXTR SNPs (i.e., rs53576-rs2254298-rs2268493) were also analyzed due to previously published associations. Results: Using the additive inheritance model in FBAT we found associations between AVPR1B SNPs (rs28632197, p = 0.005, rs35369693, p = 0.025) and diagnosis. As in other studies, OXTR rs2268493 (p = 0.050) was associated with diagnosis. rs2268493 was also associated with ASD subphenotypes of social withdrawal (p = 0.013) and Insistence on Sameness (p = 0.039). Further analyses demonstrated that the haplotype, rs2254298–rs2268493 was found to be significantly associated with diagnosis (A-T; p = 0.026). FBAT was also used to analyze AVPR1A microsatellites (RS1 and RS3). Both length variants were found to be associated with restrictive, repetitive behaviors, but not overall diagnosis

  6. ASD and genetic associations with receptors for oxytocin and vasopressin – AVPR1A, AVPR1B, and OXTR

    Directory of Open Access Journals (Sweden)

    Sunday M Francis

    2016-11-01

    Full Text Available Background: There are limited treatments available for autism spectrum disorder (ASD. Studies have reported significant associations between the receptor genes of oxytocin (OT and vasopressin (AVP and ASD diagnosis, as well as, ASD-related phenotypes. Researchers have also found the manipulation of these systems affect social and repetitive behaviors, core characteristics of ASD. Consequently, research involving the oxytocin/vasopressin pathways as intervention targets has increased. Therefore, further examination into the relationship between these neuropeptides and ASD was undertaken. In this study, we examined associations between variants in the receptor genes of vasopressin (AVPR1A, AVPR1B, oxytocin (OXTR and ASD diagnosis along with related subphenotypes.Methods: Probands were assessed using Autism Diagnostic Interview-Revised, Autism Diagnostic Observation Schedule, and clinical DSM-IV-TR criteria. Single nucleotide polymorphisms (SNPs in AVPR1B and OXTR, and microsatellites in AVPR1A were genotyped in ~200 families with a proband with ASD. Family-based association testing (FBAT was utilized to determine associations between variants and ASD. Haplotypes composed of OXTR SNPs (i.e. rs53576-rs2254298-rs2268493 were also analyzed due to previously published associations.Results: Using the additive inheritance model in FBAT we found associations between AVPR1B SNPs (rs28632197, p=0.005, rs35369693, p=0.025 and diagnosis. As in other studies, OXTR rs2268493 (p=0.050 was associated with diagnosis. rs2268493 was also associated with ASD subphenotypes of social withdrawal (p=0.013 and insistence on sameness (p=0.039. Further analyses demonstrated that the haplotype, rs2254298-rs2268493 was found to be significantly associated with diagnosis (A-T; p=0.026. FBAT was also used to analyze AVPR1A microsatellites (RS1 and RS3. Both length variants were found to be associated with restrictive, repetitive behaviors, but not overall diagnosis. Correction

  7. Re-evaluation of the prolactin receptor expression in human breast cancer

    DEFF Research Database (Denmark)

    Galsgaard, Elisabeth Douglas; Rasmussen, Birgitte Bruun; Folkesson, Charlotta Grånäs;

    2009-01-01

    and decidual cells in tissue sections of human placenta. Screening of 160 mammary adenocarcinomas demonstrated significant immunoreactivity in only four tumours, indicating that PRLR is generally not strongly upregulated in human breast cancer. However, even a very low level of PRLR expression was found......The pituitary hormone PRL is involved in tumorigenesis in rodents and humans. PRL promotes proliferation, survival and migration of cancer cells acting via the PRL receptor (PRLR). Aiming to perform a large-scale immunohistochemical (IHC) screening of human mammary carcinomas for PRLR expression...... specificity for PRLR and to rather recognise a PRLR-associated protein. The mAb U5 raised against the rat PRLR did not cross-react with the human receptor. Only one mAb, 1A2B1, was found useful for detection of PRLR in IHC applications. This antibody recognised PRLR expressed in human breast cancer cell lines...

  8. Polymorphisms of interleukin-1B and interleukin-1 receptor antagonist genes in patients with chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Ping-An Zhang; Yan Li; Pu Xu; Jian-Min Wu

    2004-01-01

    AIM: To investigate the relationships between polymorphisms of interleukin-1B (IL-1B) promoter region -511C/T and interleukin-1 receptor antagonist gene (IL-1RN) and susceptibility to chronic hepatitis B in Chinese population.METHODS: Genomic DNA was extracted from the peripheral blood of 190 patients with chronic hepatitis B and 249 normal controls and then subjected to polymerase chain reaction (PCR) amplification. The PCR products were digested by restriction endonuclease AvaI. The products of digestion were subjected to 20 g/L gel electrophoresis and ethidium bromide staining.RESULTS: The frequencies of IL-1B (-511) genotypes CC,CT and TT in patients with chronic hepatitis B were 23.7%,49.5% and 26.8%, while 26.1%, 47.4% and 26.5%respectively in controls. The results showed that there was no significant difference in the frequencies of alleles or genotypes in IL-1B between patients with chronic hepatitis B and controls. The distributions of IL-1B (-511) genotype CC were significantly different between the two subgroups (HBV-DNA ≤1×103 copies/mL as subgroup I, HBV-DNA > 1×103 copies/mL as subgroup Ⅱ) of chronic hepatitis B (P=0.029). Only four of the five kinds of polymorphism (1/1,1/2, 2/2 and 1/4) were found in this study. The frequencies of IL-1RN genotypes 1/1, 1/2, 2/2 and 1/4 were 88.9%, 9.0%,0.5% and 1.6% in patients with chronic hepatitis B respectively,while were 81.1%, 16.9%, 0.4% and 1.6% respectively in controls. The frequencies of genotype1/2 and IL-1RN allele 2 in patients with chronic hepatitis B were lower than those in controls (P=0.016 and P=0.029, respectively).CONCLUSION: There is an association between polymorphisms of the promoter region -511C/T of IL-1B and IL-1RN intron 2and chronic hepatitis B virus infection. Subjects with IL-1RN 2 may be resistant to HBV infection, and IL-1B(-511)genotype CC is closely related with HBV-DNA replication,which gives some new clues to the study of pathogenesis of chronic hepatitis B.

  9. Neonatal DSP-4 treatment impairs 5-HT(1B) receptor reactivity in adult rats. Behavioral and biochemical studies.

    Science.gov (United States)

    Ferdyn-Drosik, Marzena; Nowak, Przemysław; Bojanek, Kamila; Bałasz, Michał; Kasperski, Jacek; Skaba, Dariusz; Muchacki, Rafał; Kostrzewa, Richard M

    2010-01-01

    To examine the effect of a central noradrenergic lesion on the reactivity of the 5-HT(1B) receptor we compared intact male rats with rats in which noradrenergic nerve terminals were largely destroyed with the neurotoxin DSP-4 (50 mg/kg x 2, on the 1st and 3rd days of postnatal life). When rats attained 10 weeks of age, control and DSP-4 rats were divided into two subgroups receiving either saline or the serotonin (5-HT) synthesis inhibitor (p-chlorophenylalanine; p-CPA; 100 mg/kg). Employing an elevated plus maze test, we demonstrated that CP 94,253 (5-propoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-pyrrolo[3,2-b]pyridine hydrochloride) (4.0 mg/kg; 5-HT(1B) agonist) induced an anxiogenic-like action in control rats; however, it failed to elicit this effect in the DSP-4 group. Surprisingly, in p-CPA pretreated rats anxiogenic-like activity was observed both in control and DSP-4 treated rats. CP 94,253 significantly attenuated 5-HT synthesis in the medial prefrontal cortex (mPFC) of control rats, and SB 216641 (N-{3-[3-(dimethylamino)ethoxy]-4-methoxyphenyl}-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)-[1,1'-biphenyl]-4-carboxamide hydrochloride) (4.0 mg/kg; 5-HT(1B) antagonist) was able to antagonize this effect. Conversely, CP 94,253 failed to significantly inhibit the 5-HT synthesis rate in DSP-4-treated rats. In the microdialysis study CP 94,253 induced long-lasting attenuation of 5-HT release in the mPFC of control rats but had no effect in DSP-4 rats. These data lead to the proposal that presynaptic 5-HT(1B) autoreceptors underwent desensitization in DSP-4 treated rats.

  10. NXN-188, a selective nNOS inhibitor and a 5-HT1B/1D receptor agonist, inhibits CGRP release in preclinical migraine models

    DEFF Research Database (Denmark)

    Bhatt, Deepak K; Gupta, Saurabh; Jansen-Olesen, Inger;

    2013-01-01

    BackgroundNXN-188 is a combined neuronal nitric oxide synthase (nNOS) inhibitor and 5-hydroxytryptamine 1B/1D (5-HT(1B/1D)) receptor agonist. Using preclinical models, we evaluated whether these two unique therapeutic principles have a synergistic effect in attenuating stimulated calcitonin gene-...

  11. Interleukin-1B and Interleukin-1 Receptor Antagonist in Patients with Helicobacter pylori Associated Diseases

    Directory of Open Access Journals (Sweden)

    Elizaveta S. Ageeva, PhD

    2012-06-01

    Full Text Available The ethnic people of the Republic of Khakassia (the Khakas with ulcer disease show a significant T-cell activation and humoral immune response when compared with the Europoids. The reasons for such differences could be due to certain ethno-specific allelic variants of the interleukins, which considerably change the degree of cytokine expression. The aim was to study the peculiarities of the association of the interleukin-1 (IL-1 gene polymorphisms and interleukin-1 receptor antagonist (IL-1Ra. Patients with chronic gastritis and ulcer disease were examined using the restriction analysis method. The most wide-spread allelic variants among the Khakas were discovered to be С�� IL-1β and R4R4 IL-1Ra. In this study, we suggest the necessity to define the population’s risk and the protective genotypes that promote Helicobacter pylori-associated ulcer disease among the Khakas people.

  12. Rat insulinoma cells express both a 115-kDa growth hormone receptor and a 95-kDa prolactin receptor structurally related to the hepatic receptors

    DEFF Research Database (Denmark)

    Møldrup, Annette; Billestrup, N; Nielsen, Jens Høiriis

    1990-01-01

    Insulin-producing rat islet RIN-5AH tumor cells express multiple binding sites for human growth hormone (hGH). The effect of rat growth hormone (rGH), rat prolactin (rPRL), and human placental lactogen (hPL) on the binding of 125I-labeled hGH (125I-hGH) to RIN-5AH cells revealed the presence...

  13. Expression of a constitutively active prolactin receptor causes histone trimethylation of the p53 gene in breast cancer

    Institute of Scientific and Technical Information of China (English)

    Tan Dunyong; Tang Peizhi; Huang Jianjun; Zhang Jie; Zhou Weihua; Ameae M.Walker

    2014-01-01

    Background Prolactin (PRL) is a pituitary polypeptide hormone characterized by multiple biological actions including stimulation of growth in the prostate and formation of secretory alveoli and stimulation of milk protein gene expression in the mammary gland.PRL exerts its effect by dimerizing its receptor (PRLR) on the plasma membrane and regulating gene expression through the JAK-Stat signal pathway.We have previously described a natural variant of the PRLR in which the S2 subdomain of the extracellular domain is missing (Delta S2).Delta S2 PRLRs are dimerized in the absence of PRL and have constitutive activity in the promotion of breast cancer cell growth.Enhancer of zeste homolog 2 (EZH2),as one of the histone-modifying enzymes,is a key factor regulating gene expression by epigenetic modification.We hypothesized that these constitutive activated Delta S2 PRLRs played a pathogenic role in breast cancer in part through alterations in the expression of EZH2 and the trimethylation of histone 3 on lysine 27 (H3K27Me3).Methods In order to verify the clinical significance and to establish the link between Delta S2 PRLR expression and epigenetic change,EZH2,H3K27Me3,and Delta S2 PRLR were detected in both normal and cancerous human breast tissues.Also,overexpression of Delta S2 PRLR in breast epithelial cells was achieved by infection with adenovirus carrying the cDNA.Western blotting and chromatin immunoprecipitation (ChIP assay) and acid histone extraction were applied to detect the expression of EZH2 and the trimethylation of histone 3,respectively.Results In breast tissue,higher EZH2 expression and higher H3K27Me3 were found associated with higher Delta S2 expression in breast cancer samples.In breast epithelial cells,overexpression of Delta S2 PRLR increased EZH2 methyltransferase mRNA and protein,induced EZH2 methyltransferase recruitment to chromatin,increased the trimethylation of H3K27Me3,and decreased the expression of p53 gene.Conclusions Delta S2 PRLR

  14. Protein kinase C inhibition prevents upregulation of vascular ET(B) and 5-HT(1B) receptors and reverses cerebral blood flow reduction after subarachnoid haemorrhage in rats

    DEFF Research Database (Denmark)

    Beg, Saema S; Hansen-Schwartz, Jacob A; Vikman, Petter J;

    2007-01-01

    type 1B (5-HT(1B)) receptor upregulation and prevent the associated cerebral blood flow (CBF) reduction. The PKC inhibitor RO-31-7549 or vehicle was injected intracisternally after the induced SAH in rats (n=3 to 10 in each groups for each method). The involvement of the PKC isoforms was investigated...... by quantitative real-time polymerase chain reaction and immunohistochemistry, respectively. Administration of RO-31-7549 prevented the upregulated contraction elicited by application of ET-1 and 5-CT in cerebral arteries and kept the ET(B) and 5-HT(1B) receptor mRNA and protein levels at pre-SAH levels. Regional...

  15. Adenosine A1 receptor-mediated inhibition of in vitro prolactin secretion from the rat anterior pituitary

    Directory of Open Access Journals (Sweden)

    D.L.W. Picanço-Diniz

    2006-11-01

    Full Text Available In previous studies, we demonstrated biphasic purinergic effects on prolactin (PRL secretion stimulated by an adenosine A2 agonist. In the present study, we investigated the role of the activation of adenosine A1 receptors by (R-N6-(2-phenylisopropyladenosine (R-PIA at the pituitary level in in vitro PRL secretion. Hemipituitaries (one per cuvette in five replicates from adult male rats were incubated. Administration of R-PIA (0.001, 0.01, 0.1, 1, and 10 µM induced a reduction of PRL secretion into the medium in a U-shaped dose-response curve. The maximal reduction was obtained with 0.1 µM R-PIA (mean ± SEM, 36.01 ± 5.53 ng/mg tissue weight (t.w. treatment compared to control (264.56 ± 15.46 ng/mg t.w.. R-PIA inhibition (0.01 µM = 141.97 ± 15.79 vs control = 244.77 ± 13.79 ng/mg t.w. of PRL release was blocked by 1 µM cyclopentyltheophylline, a specific A1 receptor antagonist (1 µM = 212.360 ± 26.560 ng/mg t.w., whereas cyclopentyltheophylline alone (0.01, 0.1, 1 µM had no effect. R-PIA (0.001, 0.01, 0.1, 1 µM produced inhibition of PRL secretion stimulated by both phospholipase C (0.5 IU/mL; 977.44 ± 76.17 ng/mg t.w. and dibutyryl cAMP (1 mM; 415.93 ± 37.66 ng/mg t.w. with nadir established at the dose of 0.1 µM (225.55 ± 71.42 and 201.9 ± 19.08 ng/mg t.w., respectively. Similarly, R-PIA (0.01 µM decreased (242.00 ± 24.00 ng/mg t.w. the PRL secretion stimulated by cholera toxin (0.5 mg/mL; 1050.00 ± 70.00 ng/mg t.w.. In contrast, R-PIA had no effect (468.00 ± 34.00 ng/mg t.w. on PRL secretion stimulation by pertussis toxin (0.5 mg/mL; 430.00 ± 26.00 ng/mg t.w.. These results suggest that inhibition of PRL secretion after A1 receptor activation by R-PIA is mediated by a Gi protein-dependent mechanism.

  16. Relationship between melatonin receptor 1B and insulin receptor substrate 1 polymorphisms with gestational diabetes mellitus: a systematic review and meta-analysis.

    Science.gov (United States)

    Zhang, Yan; Sun, Cheng-Ming; Hu, Xiang-Qin; Zhao, Yue

    2014-08-22

    Studies have investigated the relationship between genetic variants and risk of gestational diabetes mellitus (GDM). However, the results remain inconclusive. The aim of this study was to investigate the association of rs10830963 and rs1387153 variants in melatonin receptor 1B (MTNR1B) and rs1801278 variant in insulin receptor substrate 1 (IRS1) with GDM susceptibility. Electronic database of PubMed, Medline, Embase, and CNKI (China National Knowledge Infrastructure) were searched for relevant studies between 2005 and 2014. The odds ratio (OR) with its 95% confidence interval (CI) were employed to estimate the association. Total ten case-control studies, including 3428 GDM cases and 4637 healthy controls, met the inclusion criteria. Our results showed a significant association between the three genetic variants and GDM risk, rs10830963 with a P-value less than 0.0001, rs1387153 with a P-value of 0.0002, and rs1801278 with a P-value of 0.001. Furthermore, all the genetic models in these three polymorphisms were associated with increased risks of GDM as well (P< = 0.009). In conclusion, our study found that the genetic polymorphisms rs10830963 and rs1387153 in MTNR1B and rs1801278 in IRS1 were associated with an increased risk of developing GDM. However, further studies with gene-gene and gene-environmental interactions should be considered.

  17. Operant learning and differential-reinforcement-of-low-rate 36-s responding in 5-HT1A and 5-HT1B receptor knockout mice.

    NARCIS (Netherlands)

    Pattij, T.; Broersen, L.M.; Linde, J. van der; Groenink, L.; Gugten, J. van der; Maes, R.A.A.; Olivier, B.

    2003-01-01

    Previous studies with mice lacking 5-HT(1A) (1AKO) and 5-HT(1B) (1BKO) receptors in hippocampus-dependent learning and memory paradigms, suggest that these receptors play an important role in learning and memory, although their precise role is unclear. In the present study, 1AKO and 1BKO mice were s

  18. Crystal Structure of Botulinum Neurotoxin Type a in Complex With the Cell Surface Co-Receptor GT1b-Insight Into the Toxin-Neuron Interaction

    Energy Technology Data Exchange (ETDEWEB)

    Stenmark, P.; Dupuy, J.; Inamura, A.; Kiso, M.; Stevens, R.C.

    2009-05-26

    Botulinum neurotoxins have a very high affinity and specificity for their target cells requiring two different co-receptors located on the neuronal cell surface. Different toxin serotypes have different protein receptors; yet, most share a common ganglioside co-receptor, GT1b. We determined the crystal structure of the botulinum neurotoxin serotype A binding domain (residues 873-1297) alone and in complex with a GT1b analog at 1.7 A and 1.6 A, respectively. The ganglioside GT1b forms several key hydrogen bonds to conserved residues and binds in a shallow groove lined by Tryptophan 1266. GT1b binding does not induce any large structural changes in the toxin; therefore, it is unlikely that allosteric effects play a major role in the dual receptor recognition. Together with the previously published structures of botulinum neurotoxin serotype B in complex with its protein co-receptor, we can now generate a detailed model of botulinum neurotoxin's interaction with the neuronal cell surface. The two branches of the GT1b polysaccharide, together with the protein receptor site, impose strict geometric constraints on the mode of interaction with the membrane surface and strongly support a model where one end of the 100 A long translocation domain helix bundle swing into contact with the membrane, initiating the membrane anchoring event.

  19. A PrP(C)-caveolin-Lyn complex negatively controls neuronal GSK3β and serotonin 1B receptor.

    Science.gov (United States)

    Hernandez-Rapp, Julia; Martin-Lannerée, Séverine; Hirsch, Théo Z; Pradines, Elodie; Alleaume-Butaux, Aurélie; Schneider, Benoît; Baudry, Anne; Launay, Jean-Marie; Mouillet-Richard, Sophie

    2014-05-08

    The cellular prion protein, PrP(C), is a glycosylphosphatidylinositol-anchored protein, abundant in lipid rafts and highly expressed in the brain. While PrP(C) is much studied for its involvement under its abnormal PrP(Sc) isoform in Transmissible Spongiform Encephalopathies, its physiological role remains unclear. Here, we report that GSK3β, a multifunctional kinase whose inhibition is neuroprotective, is a downstream target of PrP(C) signalling in serotonergic neuronal cells. We show that the PrP(C)-dependent inactivation of GSK3β is relayed by a caveolin-Lyn platform located on neuronal cell bodies. Furthermore, the coupling of PrP(C) to GSK3β potentiates serotonergic signalling by altering the distribution and activity of the serotonin 1B receptor (5-HT1BR), a receptor that limits neurotransmitter release. In vivo, our data reveal an increased GSK3β kinase activity in PrP-deficient mouse brain, as well as sustained 5-HT1BR activity, whose inhibition promotes an anxiogenic behavioural response. Collectively, our data unveil a new facet of PrP(C) signalling that strengthens neurotransmission.

  20. The effect of the Taq1A variant in the dopamine D-2 receptor gene and common CYP2D6 alleles on prolactin levels in risperidone-treated boys

    NARCIS (Netherlands)

    Roke, Yvette; van Harten, Peter N.; Franke, Barbara; Galesloot, Tessel E.; Boot, Annemieke M.; Buitelaar, Jan K.

    2013-01-01

    Objective To investigate the effect of the Taq1A variant in the Dopamine D2 receptor gene (DRD2) and common functional genetic variants in the cytochrome P450 2D6 gene (CYP2D6) on prolactin levels in risperidone-treated boys with autism spectrum disorders and disruptive behavior disorders.Methods Fo

  1. The effect of the Taq1A variant in the dopamine D2 receptor gene and common CYP2D6 alleles on prolactin levels in risperidone-treated boys

    NARCIS (Netherlands)

    Roke, Y.; Harten, P.N. van; Franke, B.; Galesloot, T.E.; Boot, A.M.; Buitelaar, J.K.

    2013-01-01

    OBJECTIVE: To investigate the effect of the Taq1A variant in the Dopamine D2 receptor gene (DRD2) and common functional genetic variants in the cytochrome P450 2D6 gene (CYP2D6) on prolactin levels in risperidone-treated boys with autism spectrum disorders and disruptive behavior disorders. METHODS:

  2. Freud-2/CC2D1B mediates dual repression of the serotonin-1A receptor gene.

    Science.gov (United States)

    Hadjighassem, Mahmoud R; Galaraga, Kimberly; Albert, Paul R

    2011-01-01

    The serotonin-1A (5-HT1A) receptor functions as a pre-synaptic autoreceptor in serotonin neurons that regulates their activity, and is also widely expressed on non-serotonergic neurons as a post-synaptic heteroreceptor to mediate serotonin action. The 5-HT1A receptor gene is strongly repressed by a dual repressor element (DRE), which is recognized by two proteins: Freud-1/CC2D1A and another unknown protein. Here we identify mouse Freud-2/CC2D1B as the second repressor of the 5-HT1A-DRE. Freud-2 shares 50% amino acid identity with Freud-1, and contains conserved structural domains. Mouse Freud-2 bound specifically to the rat 5-HT1A-DRE adjacent to, and partially overlapping, the Freud-1 binding site. By supershift assay using nuclear extracts from L6 myoblasts, Freud-2-DRE complexes were distinguished from Freud-1-DRE complexes. Freud-2 mRNA and protein were detected throughout mouse brain and peripheral tissues. Freud-2 repressed 5-HT1A promoter-reporter constructs in a DRE-dependent manner in non-neuronal (L6) or 5-HT1A-expressing neuronal (NG108-15, RN46A) cell models. In NG108-15 cells, knockdown of Freud-2 using a specific short-interfering RNA reduced endogenous Freud-2 protein levels and decreased Freud-2 bound to the 5-HT1A-DRE as detected by chromatin immunoprecipitation assay, but increased 5-HT1A promoter activity and 5-HT1A protein levels. Taken together, these data show that Freud-2 is the second component that, with Freud-1, mediates dual repression of the 5-HT1A receptor gene at the DRE.

  3. Role of 5-HT1B, 5-HT2A and 5-HT2C receptors in learning.

    Science.gov (United States)

    Meneses, A; Hong, E

    1997-08-01

    The effects of post-training (i.p.) injection of TFMPP, mCPP, DOI or 1-NP in the autoshaping learning task was explored. Furthermore, the post-training effects of these agonists after treatment with the antagonists (+/-)-pindolol, (+/-)-propranolol, NAN-190, ketanserin, ritanserin, mesulergine, MDL-72222 or p-chloroamphetamine (5-HT depleter) were studied. Rats were individually trained with a lever-press response (conditioned response; CR) on the autoshaping task and tested 24 h later. The results showed that the injection of TFMPP (1-10 mg/kg), mCPP (1-10 mg/kg), 1-NP (0.1-1.0 mg/kg) or mesulergine (0.4 mg/kg) decreased the rate of CR, while DOI (0.01-0.1 mg/kg) and ritanserin (0.5 mg/kg) and ketanserin (0.001-0.1 mg/kg) increased it. However, the effect induced by TFMPP was reversed by (+/-)-pindolol, ketanserin, ritanserin and PCA; the mCPP-induced effect was antagonized by (+/-)-propranolol, ketanserin, ritanserin and MDL-72222; and the effect produced by 1-NP was reversed by ketanserin, ritanserin and PCA. In addition, the increment in CR provoked by DOI was enhanced by ketanserin, and reversed by ritanserin, mesulergine and PCA. These findings suggest that TFMPP, 1-NP and DOI exerted their effects via stimulation of presynaptic 5-HT receptors. The effects of mCPP most probably reflect activation of postsynaptic receptors. The present data suggest that both 5-HT1B and 5-HT2A-2C receptors play a significant role in the consolidation of learning.

  4. Epidermal growth factor receptor cross-talks with ligand-occupied estrogen receptor-α to modulate both lactotroph proliferation and prolactin gene expression

    Science.gov (United States)

    Chen, Shenglin; Bangaru, Madhavi Latha Yadav; Sneade, Leighton; Dunckley, Joseph A.; Ben-Jonathan, Nira; Kansra, Sanjay

    2009-01-01

    Both estrogen (E2) and EGF regulate lactotrophs, and we recently demonstrated that EGF phosphorylates S118 on estrogen receptor-α (ERα) and requires ERα to stimulate prolactin (PRL) release. However, the interactions between ligand-occupied ERα and activated ErbB1 and its impact on lactotroph function are unknown. Using rat GH3 lactotrophs, we found that both E2 and EGF independently stimulated proliferation and PRL gene expression. Furthermore, their combination resulted in an enhanced stimulatory effect on both cell proliferation and PRL gene expression. Inhibitors of ER as well as ErbB1 blocked the combined effects of E2 and EGF. Pretreatment with UO126 abolished the combined effects, demonstrating Erk1/2 requirement. Although bidirectionality in ER-ErbB1 cross-talk is a well-accepted paradigm, interestingly in lactotrophs, ErbB1 kinase inhibitor failed to block the effect of E2 on proliferation and stimulation of PRL gene expression, suggesting that ER does not require ErbB1 to mediate its effects. Furthermore, E2 did not affect the ability of EGF to induce c-Fos expression or modulate AP-1 activity. However, both E2 and EGF combine to enhance S118 phosphorylation of ERα, leading to enhanced E2-mediated estrogen response element transactivation. Taken together, our results suggest that, in lactotrophs, activated ErbB1 phosphorylates ERα to enhance the stimulatory effect of E2, thereby providing the molecular basis by which EGF amplifies the response of E2. PMID:19470835

  5. The pituitary mediates the anxiolytic-like effects of the vasopressin V1B receptor antagonist, SSR149415, in a social interaction test in rats.

    Science.gov (United States)

    Shimazaki, Toshiharu; Iijima, Michihiko; Chaki, Shigeyuki

    2006-08-14

    A vasopressin V(1B) receptor antagonist has been shown to exhibit anxiolytic effects in a variety of animal models of anxiety. In the present study, we examined the involvement of the pituitary in the anxiolytic effects of a vasopressin V(1B) receptor antagonist by conducting a social interaction test in rats. In the sham-operated rats, both the vasopressin V(1B) receptor antagonist SSR149415 and the benzodiazepine chlordiazepoxide significantly increased the social behavior of a pair of unfamiliar rats, and the blood adrenocorticotropic hormone levels were markedly increased during the social interaction test. Hypophysectomy also increased the length of time that the animals engaged in social behavior to the same extent as that observed after treatment of the sham-operated rats with anxiolytics. However, while chlordiazepoxide further increased the duration of social interaction in the hypophysectomized rats, the anxiolytic effects of SSR149415 was no longer observed in these animals. These results suggest that the anxiolytic effects of the vasopressin V(1B) receptor antagonist in the social interaction test are mediated through blockade of the vasopressin V(1B) receptor in the pituitary.

  6. Heterogeneous Downregulation of Angiotensin II AT1-A and AT1-B Receptors in Arterioles in STZ-Induced Diabetic Rat Kidneys

    Directory of Open Access Journals (Sweden)

    Zsolt Razga

    2014-01-01

    Full Text Available Introduction. The renin granulation of kidney arterioles is enhanced in diabetes despite the fact that the level of angiotensin II in the diabetic kidney is elevated. Therefore, the number of angiotensin II AT1-A and AT1-B receptors in afferent and efferent arteriole’s renin-positive and renin-negative smooth muscle cells (SMC was estimated. Method. Immunohistochemistry at the electron microscopic level was combined with 3D stereological sampling techniques. Results. In diabetes the enhanced downregulation of AT1-B receptors in the renin-positive than in the renin-negative SMCs in both arterioles was resulted: the significant difference in the number of AT1 (AT1-A + AT1-B receptors between the two types of SMCs in the normal rats was further increased in diabetes and in contrast with the significant difference observed between the afferent and efferent arterioles in the normal animals, there was no such difference in diabetes. Conclusions. The enhanced downregulation of the AT1-B receptors in the renin-negative SMCs in the efferent arterioles demonstrates that the regulation of the glomerular filtration rate by the pre- and postglomerular arterioles is changed in diabetes. The enhanced downregulation of the AT1-B receptors in the renin-positive SMCs in the arterioles may result in an enhanced level of renin granulation in the arterioles.

  7. Effects of the 5-HT receptor antagonists GR127935 (5-HT1B/1D) and MDL100907 (5-HT2A) in the consolidation of learning.

    Science.gov (United States)

    Meneses, A; Terrón, J A; Hong, E

    1997-12-01

    We have previously reported that 5-HT1B/1D and 5-HT2A/2B/2C receptors play a role in learning and memory. The present investigation was devoted to analyze further in the autoshaping learning task: (1) the effects of the 5-HT1A/1B/1D receptor agonist, GR46611, the 5-HT1B/1D receptor antagonist, GR127935, and the selective 5-HT2A receptor antagonist, MDL100907. Consistent with a role of 5-HT1B/1D receptors in learning, the post-training injection of GR46611 (1-10 mg/kg) decreased the consolidation of learning whereas GR127935 (10 mg/kg) increased it; the effects of both drugs were reversed by PCA pretreatment. GR127935 abolished the decrease induced by GR46611, TFMPP and mCPP, whereas MDL100907 (0.1-3.0 mg/kg) had no effect by itself but abolished the effects of DOI, ketanserin and TFMPP and moderately inhibited the effects elicited by mCPP, 1-NP and mesulergine. Neither did GR127935 nor MDL100907 significantly modify the increase in the consolidation of learning induced by 8-OH-DPAT. Thus, the present findings suggest that stimulation of presynaptic 5-HT1B/1D receptors impairs the consolidation of learning whilst stimulation of 5-HT2A/2C receptors enhances it; the blockade of 5-HT2A receptors has no effects. In addition, 5-HT2 receptors seem to modulate this cognitive stage.

  8. Summary data of potency and parameter information from semi-mechanistic PKPD modeling of prolactin release following administration of the dopamine D2 receptor antagonists risperidone, paliperidone and remoxipride in rats

    Directory of Open Access Journals (Sweden)

    Amit Taneja

    2016-09-01

    Full Text Available We provide the reader with relevant data related to our recently published paper, comparing two mathematical models to describe prolactin turnover in rats following one or two doses of the dopamine D2 receptor antagonists risperidone, paliperidone and remoxipride, “A comparison of two semi-mechanistic models for prolactin release and prediction of receptor occupancy following administration of dopamine D2 receptor antagonists in rats” (Taneja et al., 2016 [1]. All information is tabulated. Summary level data on the in vitro potencies and the physicochemical properties is presented in Table 1. Model parameters required to explore the precursor pool model are presented in Table 2. In Table 3, estimated parameter comparisons for both models are presented, when separate potencies are estimated for risperidone and paliperidone, as compared to a common potency for both drugs. In Table 4, parameter estimates are compared when the drug effect is parameterized in terms of drug concentration or receptor occupancy.

  9. Differential involvement of 5-HT(1A) and 5-HT(1B/1D) receptors in human interferon-alpha-induced immobility in the mouse forced swimming test.

    Science.gov (United States)

    Zhang, Hongmei; Wang, Wei; Jiang, Zhenzhou; Shang, Jing; Zhang, Luyong

    2010-01-01

    Although Interferon-alpha (IFN-alpha, CAS 9008-11-1) is a powerful drug in treating several viral infections and certain tumors, a considerable amount of neuropsychiatric side-effects such as depression and anxiety are an unavoidable consequence. Combination with the selective serotonin (5-HT) reuptake inhibitor (SSRI) fluoxetine (CAS 56296-78-7) significantly improved the situation. However, the potential 5-HT(1A) receptor- and 5-HT(1B) receptor-signals involved in the antidepressant effects are still unclear. The effects of 5-HT(1A) receptor- and 5-HT(1B) receptor signals were analyzed by using the mouse forced swimming test (FST), a predictive test of antidepressant-like action. The present results indicated that (1) fluoxetine (administrated intragastrically, 30 mg/kg; not subactive dose: 15 mg/kg) significantly reduced IFN-alpha-induced increase of the immobility time in the forced swimming test; (2) 5-HT(1A) receptor- and 5-HT(1B) receptor ligands alone or in combination had no effects on IFN-alpha-induced increase of the immobility time in the FST; (3) surprisingly, WAY 100635 (5-HT(1A) receptor antagonist, 634908-75-1) and 8-OH-DPAT(5-HT(1A) receptor agonist, CAS 78950-78-4) markedly enhanced the antidepressant effect of fluoxetine at the subactive dose (15 mg/kg, i. g.) on the IFN-alpha-treated mice in the FST. Further investigations showed that fluoxetine combined with WAY 100635 and 8-OH-DPAT failed to produce antidepressant effects in the FST. (4) Co-application of CGS 12066A (5-HT(1B) receptor agonist, CAS 109028-09-3) or GR 127935 (5-HT(1B/1D) receptor antagonist, CAS 148642-42-6) with fluoxetine had no synergistic effects on the IFN-alpha-induced increase of immobility time in FST. (5) Interestingly, co-administration of GR 127935, WAY 100635 and fluoxetine significantly reduced the IFN-alpha-induced increase in immobility time of FST, being more effective than co-administration of WAY 100635 and fluoxetine. All results suggest that (1) compared to

  10. Estimated glomerular filtration rate in sickle cell anemia is associated with polymorphisms of bone morphogenetic protein receptor 1B.

    Science.gov (United States)

    Nolan, Vikki G; Ma, Qianli; Cohen, Herbert T; Adewoye, Adeboye; Rybicki, Anne C; Baldwin, Clinton; Mahabir, Rhea N; Homan, Erica P; Wyszynski, Diego F; Fabry, Mary E; Nagel, Ronald L; Farrer, Lindsay A; Steinberg, Martin H

    2007-03-01

    Renal disease is common in sickle cell anemia. In this exploratory work, we used data from a longitudinal study of the natural history of sickle cell disease to examine the hypothesis that polymorphisms (SNPs) in selected candidate genes are associated with glomerular filtration rate (GFR). DNA samples and clinical and laboratory data were available for 1,140 patients with sickle cell anemia. GFR was estimated using the Cockcroft-Gault and Schwartz formulas for adults and children, respectively. We examined approximately 175 haplotype tagging (ht) SNPs in about 70 genes of the TGFbeta/BMP pathway for their association with GFR using linear regression. Four SNPs in BMPR1B, a bone morphogenetic protein (BMP) receptor gene, yielded statistically significant associations (P values ranging from 0.015 to 0.046). Three haplotypes in this gene were also associated with GFR. The TGF-beta/BMP pathway has been associated with the development of diabetic nephropathy, which has some features in common with sickle cell nephropathy. Our results suggest that, as with other subphenotypes of sickle cell disease, renal function may be genetically modulated.

  11. α1B-Adrenergic receptor signaling controls circadian expression of Tnfrsf11b by regulating clock genes in osteoblasts

    Directory of Open Access Journals (Sweden)

    Takao Hirai

    2015-11-01

    Full Text Available Circadian clocks are endogenous and biological oscillations that occur with a period of <24 h. In mammals, the central circadian pacemaker is localized in the suprachiasmatic nucleus (SCN and is linked to peripheral tissues through neural and hormonal signals. In the present study, we investigated the physiological function of the molecular clock on bone remodeling. The results of loss-of-function and gain-of-function experiments both indicated that the rhythmic expression of Tnfrsf11b, which encodes osteoprotegerin (OPG, was regulated by Bmal1 in MC3T3-E1 cells. We also showed that REV-ERBα negatively regulated Tnfrsf11b as well as Bmal1 in MC3T3-E1 cells. We systematically investigated the relationship between the sympathetic nervous system and the circadian clock in osteoblasts. The administration of phenylephrine, a nonspecific α1-adrenergic receptor (AR agonist, stimulated the expression of Tnfrsf11b, whereas the genetic ablation of α1B-AR signaling led to the alteration of Tnfrsf11b expression concomitant with Bmal1 and Per2 in bone. Thus, this study demonstrated that the circadian regulation of Tnfrsf11b was regulated by the clock genes encoding REV-ERBα (Nr1d1 and Bmal1 (Bmal1, also known as Arntl, which are components of the core loop of the circadian clock in osteoblasts.

  12. Combinations of physiologic estrogens with xenoestrogens alter calcium and kinase responses, prolactin release, and membrane estrogen receptor trafficking in rat pituitary cells

    Directory of Open Access Journals (Sweden)

    Watson Cheryl S

    2010-10-01

    Full Text Available Abstract Background Xenoestrogens such as alkylphenols and the structurally related plastic byproduct bisphenol A have recently been shown to act potently via nongenomic signaling pathways and the membrane version of estrogen receptor-α. Though the responses to these compounds are typically measured individually, they usually contaminate organisms that already have endogenous estrogens present. Therefore, we used quantitative medium-throughput screening assays to measure the effects of physiologic estrogens in combination with these xenoestrogens. Methods We studied the effects of low concentrations of endogenous estrogens (estradiol, estriol, and estrone at 10 pM (representing pre-development levels, and 1 nM (representing higher cycle-dependent and pregnancy levels in combinations with the same levels of xenoestrogens in GH3/B6/F10 pituitary cells. These levels of xenoestrogens represent extremely low contamination levels. We monitored calcium entry into cells using Fura-2 fluorescence imaging of single cells. Prolactin release was measured by radio-immunoassay. Extracellular-regulated kinase (1 and 2 phospho-activations and the levels of three estrogen receptors in the cell membrane (ERα, ERβ, and GPER were measured using a quantitative plate immunoassay of fixed cells either permeabilized or nonpermeabilized (respectively. Results All xenoestrogens caused responses at these concentrations, and had disruptive effects on the actions of physiologic estrogens. Xenoestrogens reduced the % of cells that responded to estradiol via calcium channel opening. They also inhibited the activation (phosphorylation of extracellular-regulated kinases at some concentrations. They either inhibited or enhanced rapid prolactin release, depending upon concentration. These latter two dose-responses were nonmonotonic, a characteristic of nongenomic estrogenic responses. Conclusions Responses mediated by endogenous estrogens representing different life stages are

  13. Prolactin receptor attenuation induces zinc pool redistribution through ZnT2 and decreases invasion in MDA-MB-453 breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Bostanci, Zeynep, E-mail: zbostanci@hmc.psu.edu [The Pennsylvania State University, Department of Nutritional Sciences, 209 Chandlee Lab, University Park, PA 16802 (United States); The Pennsylvania State University Milton S. Hershey Medical Center, Department of Surgery, 500 University Dr., Hershey, PA 17033 (United States); Alam, Samina, E-mail: sra116@psu.edu [The Pennsylvania State University, Department of Nutritional Sciences, 209 Chandlee Lab, University Park, PA 16802 (United States); The Pennsylvania State University Milton S. Hershey Medical Center, Department of Surgery, 500 University Dr., Hershey, PA 17033 (United States); Soybel, David I., E-mail: dsoybel@hmc.psu.edu [The Pennsylvania State University, Department of Nutritional Sciences, 209 Chandlee Lab, University Park, PA 16802 (United States); The Pennsylvania State University Milton S. Hershey Medical Center, Department of Surgery, 500 University Dr., Hershey, PA 17033 (United States); The Pennsylvania State University College of Medicine, Department of Cell and Molecular Physiology, 500 University Dr., Hershey, PA 17033 (United States); Kelleher, Shannon L., E-mail: slk39@psu.edu [The Pennsylvania State University, Department of Nutritional Sciences, 209 Chandlee Lab, University Park, PA 16802 (United States); The Pennsylvania State University Milton S. Hershey Medical Center, Department of Surgery, 500 University Dr., Hershey, PA 17033 (United States); The Pennsylvania State University College of Medicine, Department of Cell and Molecular Physiology, 500 University Dr., Hershey, PA 17033 (United States)

    2014-02-15

    Prolactin receptor (PRL-R) activation regulates cell differentiation, proliferation, cell survival and motility of breast cells. Prolactin (PRL) and PRL-R over-expression are strongly implicated in breast cancer, particularly contributing to tumor growth and invasion in the more aggressive estrogen-receptor negative (ER−) disease. PRL-R antagonists have been suggested as potential therapeutic agents; however, mechanisms through which PRL-R antagonists exert their actions are not well-understood. Zinc (Zn) is a regulatory factor for over 10% of the proteome, regulating critical cell processes such as proliferation, cell signaling, transcription, apoptosis and autophagy. PRL-R signaling regulates Zn metabolism in breast cells. Herein we determined effects of PRL-R attenuation on cellular Zn metabolism and cell function in a model of ER-, PRL-R over-expressing breast cancer cells (MDA-MB-453). PRL-R attenuation post-transcriptionally increased ZnT2 abundance and redistributed intracellular Zn pools into lysosomes and mitochondria. ZnT2-mediated lysosomal Zn sequestration was associated with reduced matrix metalloproteinase 2 (MMP-2) activity and decreased invasion. ZnT2-mediated Zn accumulation in mitochondria was associated with increased mitochondrial oxidation. Our results suggest that PRL-R antagonism in PRL-R over-expressing breast cancer cells may reduce invasion through the redistribution of intracellular Zn pools critical for cellular function. - Highlights: • PRL-R attenuation increased ZnT2 expression. • PRL-R attenuation increased lysosomal and mitochondrial Zn accumulation. • PRL-R attenuation decreased MMP-2 and invasion. • PRL-R antagonists may modulate lysosomal and mitochondrial Zn pools.

  14. Polysynaptic excitatory postsynaptic potentials that trigger spasms after spinal cord injury in rats are inhibited by 5-HT1B and 5-HT1F receptors.

    Science.gov (United States)

    Murray, Katherine C; Stephens, Marilee J; Rank, Michelle; D'Amico, Jessica; Gorassini, Monica A; Bennett, David J

    2011-08-01

    Sensory afferent transmission and associated spinal reflexes are normally inhibited by serotonin (5-HT) derived from the brain stem. Spinal cord injury (SCI) that eliminates this 5-HT innervation leads to a disinhibition of sensory transmission and a consequent emergence of unusually long polysynaptic excitatory postsynaptic potentials (EPSPs) in motoneurons. These EPSPs play a critical role in triggering long polysynaptic reflexes (LPRs) that initiate muscles spasms. In the present study we examined which 5-HT receptors modulate the EPSPs and whether these receptors adapt to a loss of 5-HT after chronic spinal transection in rats. The EPSPs and associated LPRs recorded in vitro in spinal cords from chronic spinal rats were consistently inhibited by 5-HT(1B) or 5-HT(1F) receptor agonists, including zolmitriptan (5-HT(1B/1D/1F)) and LY344864 (5-HT(1F)), with a sigmoidal dose-response relation, from which we computed the 50% inhibition (EC(50)) and potency (-log EC(50)). The potencies of 5-HT receptor agonists were highly correlated with their binding affinity to 5-HT(1B) and 5-HT(1F) receptors, and not to other 5-HT receptors. Zolmitriptan also inhibited the LPRs and general muscle spasms recorded in vivo in the awake chronic spinal rat. The 5-HT(1B) receptor antagonists SB216641 and GR127935 and the inverse agonist SB224289 reduced the inhibition of LPRs by 5-HT(1B) agonists (zolmitriptan). However, when applied alone, SB224289, SB216641, and GR127935 had no effect on the LPRs, indicating that 5-HT(1B) receptors do not adapt to chronic injury, remaining silent, without constitutive activity. The reduction in EPSPs with zolmitriptan unmasked a large glycine-mediated inhibitory postsynaptic current (IPSC) after SCI. This IPSC and associated chloride current reversed at -73 mV, slightly below the resting membrane potential. Zolmitriptan did not change motoneuron properties. Our results demonstrate that 5-HT(1B/1F) agonists, such as zolmitriptan, can restore inhibition

  15. Periaqueductal gray knockdown of V2, not V1a and V1b receptor influences nociception in the rat. yj6676@yahoo.com.

    Science.gov (United States)

    Yang, Jun; Yang, Yu; Chen, Jian-Min; Wang, Gen; Xu, Hong-Tao; Liu, Wen-Yan; Lin, Bao-Cheng

    2007-01-01

    Our pervious study has proved that arginine vasopressin (AVP) in periaqueductal gray (PAG) plays a role in antinociception. After establishing a model of local special gene knockdown, the nociceptive effect of vasopressin receptor subunit in PAG was investigated in the rat. Microinjection of short-interfering RNA (siRNA) into PAG, which targeted vasopressin receptor subtypes (V(1a), V(1b) and V(2)), locally weakened the associated mRNA expression and depressed the related receptor synthesis in a dose-dependent manner, in which the significant inhibitive effect occurred on from 7th day to 14th day following 1microg or 2microg siRNA administration. PAG knockdown of V(2) receptor gene markedly decreased pain threshold in from 6th day to 13th day after siRNA administration, whereas local knockdown of either V(1a) or V(1b) receptor gene could not influence pain threshold. The data suggest that V(2) rather than V(1a) and V(1b) receptor in PAG involves in nociception.

  16. Endothelium-dependent relaxant responses to selective 5-HT(1B/1D) receptor agonists in the isolated middle cerebral artery of the rat

    DEFF Research Database (Denmark)

    Hansen-Schwartz, Jacob; Løvland Hoel, Natalie; Nilsson, Elisabeth;

    2003-01-01

    perfused. Luminally added 5- hydroxytryptamine (5-HT), sumatriptan and rizatriptan induced maximal dilatations of 22 +/- 4, 10 +/- 2 and 13 +/- 5%, respectively, compared to the resting diameter. The relaxant effect of sumatriptan was blocked by the 5- HT(1B/1D) receptor selective antagonist GR 55562 (10...

  17. Protein kinase mediated upregulation of endothelin A, endothelin B and 5-hydroxytryptamine 1B/1D receptors during organ culture in rat basilar artery

    DEFF Research Database (Denmark)

    Hansen-Schwartz, Jacob; Svensson, Carl-Lennart; Xu, Cang-Bao;

    2002-01-01

    had an enhancing effect on the induced changes giving rise to a 7-25% increase in E(max) in response to ET-1, S6c and 5-CT as compared to the cultured control. 5. Staurosporine inhibited the culture induced upregulation of the response of both the ET(A) and the 5-HT(1B/1D) receptors, but had...

  18. Activation of 5-HT1B receptors suppresses low but not high frequency synaptic transmission in the rat subicular cortex in vitro

    NARCIS (Netherlands)

    Boeijinga, PH; Boddeke, HWGM

    1996-01-01

    We have shown previously that activation of 5-HT1B serotonin receptors mediates suppression of the amplitude of evoked potentials in the subiculum [2]. Here we show that after application of 5-HT (10 mu M), excitatory postsynaptic potentials of subicular neurons have reduced amplitudes with no chang

  19. Activation of 5-HT(1B) receptors suppresses low but not high frequency synaptic transmission in the rat subicular cortex in vitro

    NARCIS (Netherlands)

    Boeijinga, P.H.; Boddeke, H.W.G.M.

    1996-01-01

    We have shown previously that activation of 5-HT(1B) serotonin receptors mediates suppression of the amplitude of evoked potentials in the subiculum [2]. Here we show that after application of 5-HT (10 μM), excitatory postsynaptic potentials of subicular neurons have reduced amplitudes with no chang

  20. Role of alpha 1- and alpha 2-adrenergic receptors in the growth hormone and prolactin response to insulin-induced hypoglycemia in man.

    Science.gov (United States)

    Tatár, P; Vigas, M

    1984-09-01

    The effects of intravenous infusion of the nonselective alpha-adrenergic antagonist phentolamine or of the selective alpha 2-adrenergic antagonist yohimbine on growth hormone (GH), prolactin (PRL) and cortisol secretion during insulin-induced hypoglycemia were studied in 11 healthy young men. The GH response was blunted following each antagonist used, PRL secretion was higher after yohimbine and diminished after phentolamine when compared to controls. The plasma cortisol response was not influenced by either compound. In another series of experiments no effect of an oral administration of prazosin, a selective alpha 1-adrenergic antagonist, on the secretion of GH, PRL and cortisol was found in any of 7 subjects. Prazosin inhibited blood pressure increase during hypoglycemia and induced slight drowsiness and fatigue in the subjects. It is concluded that in man alpha-adrenergic stimulation of GH secretion during hypoglycemia is transmitted via alpha 2-receptors, PRL secretion is mediated via alpha 1-receptors, whereas inhibition of PRL release is mediated via alpha 2-receptors. In this experiment no effect of alpha 1- or alpha 2-blockade on cortisol response to hypoglycemia was seen.

  1. Metformin suppresses CYP1A1 and CYP1B1 expression in breast cancer cells by down-regulating aryl hydrocarbon receptor expression

    Energy Technology Data Exchange (ETDEWEB)

    Do, Minh Truong; Kim, Hyung Gyun; Tran, Thi Thu Phuong; Khanal, Tilak; Choi, Jae Ho [Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon (Korea, Republic of); Chung, Young Chul [Department of Food Science and Culinary, International University of Korea, Jinju (Korea, Republic of); Jeong, Tae Cheon, E-mail: taecheon@ynu.ac.kr [College of Pharmacy, Yeungnam University, Gyeongsan (Korea, Republic of); Jeong, Hye Gwang, E-mail: hgjeong@cnu.ac.kr [Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon (Korea, Republic of)

    2014-10-01

    Induction of cytochrome P450 (CYP) 1A1 and CYP1B1 by environmental xenobiotic chemicals or endogenous ligands through the activation of the aryl hydrocarbon receptor (AhR) has been implicated in a variety of cellular processes related to cancer, such as transformation and tumorigenesis. Here, we investigated the effects of the anti-diabetes drug metformin on expression of CYP1A1 and CYP1B1 in breast cancer cells under constitutive and inducible conditions. Our results indicated that metformin down-regulated the expression of CYP1A1 and CYP1B1 in breast cancer cells under constitutive and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced conditions. Down-regulation of AhR expression was required for metformin-mediated decreases in CYP1A1 and CYP1B1 expression, and the metformin-mediated CYP1A1 and CYP1B1 reduction is irrelevant to estrogen receptor α (ERα) signaling. Furthermore, we found that metformin markedly down-regulated Sp1 protein levels in breast cancer cells. The use of genetic and pharmacological tools revealed that metformin-mediated down-regulation of AhR expression was mediated through the reduction of Sp1 protein. Metformin inhibited endogenous AhR ligand-induced CYP1A1 and CYP1B1 expression by suppressing tryptophan-2,3-dioxygenase (TDO) expression in MCF-7 cells. Finally, metformin inhibits TDO expression through a down-regulation of Sp1 and glucocorticoid receptor (GR) protein levels. Our findings demonstrate that metformin reduces CYP1A1 and CYP1B1 expression in breast cancer cells by down-regulating AhR signaling. Metformin would be able to act as a potential chemopreventive agent against CYP1A1 and CYP1B1-mediated carcinogenesis and development of cancer. - Graphical abstract: Schematic of the CYP1A1 and CYP1B1 gene regulation by metformin. - Highlights: • Metformin inhibits CYP1A1 and CYP1B1 expression. • Metformin down-regulates the AhR signaling. • Metformin reduces Sp1 protein expression. • Metformin suppresses TDO expression.

  2. Development of a PET radioligand for the central 5-HT{sub 1B} receptor: radiosynthesis and characterization in cynomolgus monkeys of eight radiolabeled compounds

    Energy Technology Data Exchange (ETDEWEB)

    Andersson, Jan D., E-mail: j.d.andersson@ki.s [Psychiatry Section, Department of Clinical Neuroscience, Karolinska Institutet, Karolinska University Hospital, SE-17176 Stockholm (Sweden); Pierson, M. Edward [AstraZeneca Pharmaceuticals, CNS Discovery, Wilmington, DE 19850 (United States); Finnema, Sjoerd J.; Gulyas, Balazs [Psychiatry Section, Department of Clinical Neuroscience, Karolinska Institutet, Karolinska University Hospital, SE-17176 Stockholm (Sweden); Heys, Richard; Elmore, Charles S. [AstraZeneca Pharmaceuticals, CNS Discovery, Wilmington, DE 19850 (United States); Farde, Lars [AstraZeneca Pharmaceuticals, Neuroscience Clinical, SE-15185 Soedertaelje (Sweden); Halldin, Christer [Psychiatry Section, Department of Clinical Neuroscience, Karolinska Institutet, Karolinska University Hospital, SE-17176 Stockholm (Sweden)

    2011-02-15

    Introduction: The serotonin 1B (5-HT{sub 1B}) receptor has been implicated in several psychiatric disorders and is a potential pharmacological target in the treatment of depression. The aim of this study was to develop a radioligand for positron emission tomography (PET) imaging of the 5-HT{sub 1B} receptor in the primate brain in vivo. Methods: Eight carboxamide radioligands (1-8) from three different core structures were radiolabeled with carbon-11 employing N-methylation with [{sup 11}C]methyl triflate on the piperazine structural moiety. In vivo PET evaluation of each radioligand was performed in cynomolgus monkeys and included analysis of radioactive metabolites measured in plasma using high-performance liquid chromatography. Results: In a total of 12 radiosynthesis of the eight radioligands, the mean decay corrected yield was 11%, and the mean specific radioactivity was 299 GBq/{mu}mol (8075 Ci/mmol) at time of administration. Of the eight tested candidates, [{sup 11}C]6 demonstrated the most promising in vivo characteristics, showing high binding in 5-HT{sub 1B} receptor-rich regions and low binding in the cerebellum. When inspecting data from all eight compounds, lipophilicity appeared as a physicochemical property that could be related to favorable in vivo imaging characteristics. Conclusion: Candidate [{sup 11}C]6, i.e., [{sup 11}C]AZ10419369, exhibited high binding potentials in regions known to contain 5-HT{sub 1B} receptors and was nominated for further preclinical characterization and PET examination in human subjects.

  3. Structural and thermodynamic bases for the design of pure prolactin receptor antagonists: X-ray structure of Del1-9-G129R-hPRL

    DEFF Research Database (Denmark)

    Jomain, Jean-Baptiste; Tallet, Estelle; Broutin, Isabelle;

    2007-01-01

    Competitive antagonists of the human prolactin (hPRL) receptor are a novel class of molecules of potential therapeutic interest in the context of cancer. We recently developed the pure antagonist Del1-9-G129R-hPRL by deleting the nine N-terminal residues of G129R-hPRL, a first generation partial...... antagonist. We determined the crystallographic structure of Del1-9-G129R-hPRL, which revealed no major change compared with wild type hPRL, indicating that its pure antagonistic properties are intrinsically due to the mutations. To decipher the molecular bases of pure antagonism, we compared the biological...... agonism can be abolished either by further disrupting hormone site 2-receptor contacts by N-terminal deletion, as in Del1-9-G129R-hPRL, or by stabilizing hPRL and constraining its intrinsic flexibility, as in G129V-hPRL. Udgivelsesdato: 2007-Nov-9...

  4. Correlation of prolactin levels and PRL-receptor expression with Stat and Mapk cell signaling in the prostate of long-term sexually active rats.

    Science.gov (United States)

    Rojas-Durán, Fausto; Pascual-Mathey, Luz I; Serrano, Karina; Aranda-Abreu, Gonzalo E; Manzo, Jorge; Soto-Cid, Abraham H; Hernandez, Ma Elena

    2015-01-01

    Prolactin (PRL) is a key hormone for prostate function, with a basal level in serum and associated with two characteristic circadian peaks. In the male rat, the execution of one bout of sexual behavior with consecutive ejaculations produces a significant transient increase in PRL. However, the impact of a constant sexual life on both PRL levels and prostate function is unknown. Thus, by using constantly copulating males we analyzed the levels of serum PRL, the effect on prostate PRL receptors, and activation of pStat3, pStat5 and Mapk signaling pathways. Sexually experienced Wistar male rats were used, which underwent periodic sessions of sexual behavior tests. Males were subjected to a session of sexual behavior to achieve at least one and up to four ejaculations. Of these, a blood sample was collected from randomly selected males and the ventral prostate was removed for analysis. Serum PRL was quantified, the mRNA for PRL receptors was determined, and signaling pathways were analyzed. Data show that a constant sexual life produced a constant elevation of PRL in serum during four consecutive ejaculations. The ventral prostate showed a different mRNA expression profile for the long and short isoform of the PRL receptor, and both mRNA levels increased. Although the gland did not show modification of the activation of the pStat5 signaling pathway, the levels of pStat3 increased, and the Mapk pathway showed one significant elevation after the third ejaculation. Thus, we showed that an active and constant sexual life produces a sustained increase in serum PRL, its receptors, and the pStat3 signaling pathway. These responses seem to underlie the required physiological need to produce the quantity and quality of prostatic semen to ensure the appropriate environment for sperm to reach and fertilize the ovum.

  5. The tumor necrosis factor receptor superfamily member 1B polymorphisms predict response to anti-TNF therapy in patients with autoimmune disease: A meta-analysis.

    Science.gov (United States)

    Chen, Wenjuan; Xu, Hui; Wang, Xiuxiu; Gu, Junying; Xiong, Huizi; Shi, Yuling

    2015-09-01

    Numerous published data on the tumor necrosis factor receptor superfamily member 1B (TNFRSF1B) gene polymorphisms are shown to be associated with response or non-response to anti-TNF therapy in autoimmune diseases such as rheumatoid arthritis (RA), psoriasis and Crohn's Disease (CD). The aim of this study is to investigate whether the TNFRSF1B rs1061622 T/G or TNFRSF1A A/G rs767455 polymorphisms can predict the response to anti-TNF-based therapy in patients with autoimmune diseases. We conducted a meta-analysis of studies on the association between TNFRSF1B rs1061622 T/G polymorphism or TNFRSF1A A/G rs767455 polymorphism and non-responsiveness to anti-TNF therapy in autoimmune diseases. A total of 8 studies involving 929 subjects for TNFRSF1B rs1061622 and 564 subjects for TNFRSF1A rs767455 were finally considered. These studies consisted of seven studies on the TNFRSF1B polymorphism and four studies on the TNFRSF1A polymorphism. Meta-analysis showed significant association between the TNFRSF1B rs1061622 allele and non-responders to anti-TNF therapy [T/G odds ratio (OR) 0.72, 95% confidence interval (CI) 0.57-0.93, p=0.01]. Stratification by disease type indicated an association between the TNFRSF1B rs1061622 allele and non-responders to TNF antagonist in RA (T/G OR 0.69, 95% CI 0.48-0.99, pautoimmune diseases. The genotyping of this polymorphism could help to optimize the treatment by identifying patients with a likely poor response to biological drugs.

  6. Down-regulation of 5-HT1B and 5-HT1D receptors inhibits proliferation, clonogenicity and invasion of human pancreatic cancer cells.

    Directory of Open Access Journals (Sweden)

    Nilgun Gurbuz

    Full Text Available Pancreatic ductal adenocarcinoma is characterized by extensive local tumor invasion, metastasis and early systemic dissemination. The vast majority of pancreatic cancer (PaCa patients already have metastatic complications at the time of diagnosis, and the death rate of this lethal type of cancer has increased over the past decades. Thus, efforts at identifying novel molecularly targeted therapies are priorities. Recent studies have suggested that serotonin (5-HT contributes to the tumor growth in a variety of cancers including prostate, colon, bladder and liver cancer. However, there is lack of evidence about the impact of 5-HT receptors on promoting pancreatic cancer. Having considered the role of 5-HT-1 receptors, especially 5-HT1B and 5-HT1D subtypes in different types of malignancies, the aim of this study was to investigate the role of 5-HT1B and 5-HT1D receptors in PaCa growth and progression and analyze their potential as cytotoxic targets. We found that knockdown of 5-HT1B and 5-HT1D receptors expression, using specific small interfering RNA (siRNA, induced significant inhibition of proliferation and clonogenicity of PaCa cells. Also, it significantly suppressed PaCa cells invasion and reduced the activity of uPAR/MMP-2 signaling and Integrin/Src/Fak-mediated signaling, as integral tumor cell pathways associated with invasion, migration, adhesion, and proliferation. Moreover, targeting 5-HT1B and 5-HT1D receptors down-regulates zinc finger ZEB1 and Snail proteins, the hallmarks transcription factors regulating epithelial-mesenchymal transition (EMT, concomitantly with up-regulating of claudin-1 and E-Cadherin. In conclusion, our data suggests that 5-HT1B- and 5-HT1D-mediated signaling play an important role in the regulation of the proliferative and invasive phenotype of PaCa. It also highlights the therapeutic potential of targeting of 5-HT1B/1D receptors in the treatment of PaCa, and opens a new avenue for biomarkers identification

  7. Role of 5-HT(1A) and 5-HT(1B) receptors in the antidepressant-like effect of piperine in the forced swim test.

    Science.gov (United States)

    Mao, Qing-Qiu; Huang, Zhen; Ip, Siu-Po; Xian, Yan-Fang; Che, Chun-Tao

    2011-10-24

    Our previous studies have showed that treating mice with piperine significantly decreased the immobility time of the animals in the forced swim test and tail suspension test, which was related to up-regulation of serotonin (5-HT) level in the brain. The purpose of this study is to explore the contribution of 5-HT receptors in the antidepressant-like effect of piperine. The results showed that pre-treating mice with methiothepin (a non-selective 5-HT receptor antagonist, 0.1mg/kg, intraperitoneally), 4-(2'-methoxy-phenyl)-1-[2'-(n-2″-pyridinyl)-p-iodobenzamino-]ethyl-piperazine (a selective 5-HT(1A) receptor antagonist, 1mg/kg, subcutaneously) or 1-(2-(1-pyrrolyl)-phenoxy)-3-isopropylamino-2-propanol (a 5-HT(1B) receptor antagonist, 2.5mg/kg, intraperitoneally) was found to abolish the anti-immobility effect of piperine (10mg/kg, intraperitoneally) in the forced swim test. On the other hand, a sub-effective dose of piperine (1mg/kg, intraperitoneally) produced a synergistic antidepressant-like effect with (+)-8-hydroxy-2-(di-n-propylamino)tetralin (a 5-HT(1A) receptor agonist, 1mg/kg, intraperitoneally) or anpirtoline (a 5-HT(1B) receptor agonist, 0.25mg/kg, intraperitoneally). Taken together, these results suggest that the antidepressant-like effect of piperine in the mouse forced swim test may be mediated, at least in part, by the activation of 5-HT(1A) and 5-HT(1B) receptors.

  8. Effects of sex and pregnancy hormones on growth hormone and prolactin receptor gene expression in insulin-producing cells

    DEFF Research Database (Denmark)

    Møldrup, Annette; Petersen, Elisabeth D.; Nielsen, Jens Høiriis

    1993-01-01

    of islet cells to these hormones is regulated on the receptor level, GH and PRL receptor gene expression was studied in pancreata from male rats and virgin, pregnant, and lactating female rats and in cultured islets and insulinoma cells (RIN-5AH) in response to various hormones. The mRNA levels were...... quantitated by ribonuclease protection assay, using probes specific for mRNA encoding, extracellular and intracellular domains of the GH receptor, and short and long forms of the PRL receptor, respectively. Specific transcripts for the GH receptor were present in pancreas, islets, and RIN-5AH cells...

  9. High-resolution imaging of brain 5-HT{sub 1B} receptors in the rhesus monkey using [{sup 11}C]P943

    Energy Technology Data Exchange (ETDEWEB)

    Nabulsi, Nabeel; Huang Yiyun; Weinzimmer, David; Ropchan, Jim; Frost, James J. [Yale PET Center, Department of Diagnostic Radiology and Psychiatry, Yale University School of Medicine, P.O. Box 208048, New Haven, CT 06520-8048 (United States); McCarthy, Timothy [Pfizer Global R and D, Groton, CT 06340 (United States); Carson, Richard E.; Ding Yushin [Yale PET Center, Department of Diagnostic Radiology and Psychiatry, Yale University School of Medicine, P.O. Box 208048, New Haven, CT 06520-8048 (United States)

    2010-02-15

    The serotonin 5-HT{sub 1B} receptors regulate the release of serotonin and are involved in various disease states, including depression and schizophrenia. The goal of the study was to evaluate a high affinity and high selectivity antagonist, [{sup 11}C]P943, as a positron emission tomography (PET) tracer for imaging the 5-HT{sub 1B} receptor. [{sup 11}C]P943 was synthesized via N-methylation of the precursor with [{sup 11}C]methyl iodide or [{sup 11}C]methyl triflate using automated modules. The average radiochemical yield was approx. 10% with radiochemical purity of >99% and specific activity of 8.8{+-}3.6 mCi/nmol at the end-of-synthesis (n=37). PET imaging was performed in non-human primates with a high-resolution research tomograph scanner with a bolus/infusion paradigm. Binding potential (BP{sub ND}) was calculated using the equilibrium ratios of regions to cerebellum. The tracer uptake was highest in the globus pallidus and occipital cortex, moderate in basal ganglia and thalamus, and lowest in the cerebellum, which is consistent with the known brain distribution of 5-HT{sub 1B} receptors. Infusion of tracer at different specific activities (by adding various amount of unlabeled P943) reduced BP{sub ND} values in a dose-dependent manner, demonstrating the saturability of the tracer binding. Blocking studies with GR127935 (2 mg/kg iv), a selective 5-HT{sub 1B}/5-HT{sub 1D} antagonist, resulted in reduction of BP{sub ND} values by 42-95% across regions; for an example, in occipital region from 0.71 to 0.03, indicating a complete blockade. These results demonstrate the saturability and specificity of [{sup 11}C]P943 for 5-HT{sub 1B} receptors, suggesting its suitability as a PET radiotracer for in vivo evaluations of the 5-HT{sub 1B} receptor system in humans.

  10. ERK1/2 inhibition attenuates cerebral blood flow reduction and abolishes ET(B) and 5-HT(1B) receptor upregulation after subarachnoid hemorrhage in rat

    DEFF Research Database (Denmark)

    Beg, Saema A S; Hansen-Schwartz, Jacob A; Vikman, Petter J

    2006-01-01

    -regulated kinase (ERK1/2). In the present study, we hypothesized that inhibition of ERK1/2 alters the ET(B) and 5-HT(1B) receptor upregulation and at the same time prevents the sustained cerebral blood flow (CBF) reduction associated with SAH. The ERK1/2 inhibitor SB386023-b was injected intracisternally...... in conjunction with and after the induced SAH in rats. At 2 days after the SAH, cerebral arteries were harvested for quantitative real-time polymerase chain reaction, immunohistochemistry and analysis of contractile responses to endothelin-1 (ET-1; ET(A) and ET(B) receptor agonist) and 5-carboxamidotryptamine (5...

  11. The relevance of preclinical research models for the development of antimigraine drugs: Focus on 5-HT1B/1D and CGRP receptors

    DEFF Research Database (Denmark)

    Gupta, S.; Villalon, C.M.

    2010-01-01

    approaches, have significantly contributed to the two antimigraine principles in therapeutics, namely: 5-HT1B/1D receptor agonists (known as triptans) and CGRP receptor antagonists (known as gepants). This review will analyze the preclinical experimental models currently known for the development...... of these therapeutic principles, which are mainly based on the vascular and/or neurogenic theories of migraine pathogenesis. These include models based on the involvement of cranial vasodilatation and/or the trigeminovascular system in migraine. Clearly, the preclinical strategies should involve both approaches, while...

  12. Permanent Distal Occlusion of Middle Cerebral Artery in Rat Causes Local Increased ETB, 5-HT1B and AT1 Receptor-Mediated Contractility Downstream of Occlusion

    DEFF Research Database (Denmark)

    Rasmussen, Marianne N P; Hornbak, Malene; Larsen, Stine S;

    2013-01-01

    a model of permanent distal occlusion of rat middle cerebral arteries, we investigated whether there was a regional difference in receptor-mediated contractility of segments located upstream and downstream of the occlusion site. The contractile response to endothelin, angiotensin and 5-hydroxytryptamine...... occlusion without significant visible infarct resulted in locally increased ETB, angiotensin type 1 and 5-hydroxytryptamine 1B receptor-mediated contractile responses only in segments located downstream of the occlusion site. This suggests lack of wall stress as an initiating trigger leading to regulation...

  13. Antiproliferative effect of the Ginkgo biloba extract is associated with the enhancement of cytochrome P450 1B1 expression in estrogen receptor-negative breast cancer cells.

    Science.gov (United States)

    Zhao, Xiao-Dan; Dong, Ni; Man, Hong-Tao; Fu, Zhong-Lin; Zhang, Mei-Hong; Kou, Shuang; Ma, Shi-Liang

    2013-09-01

    Ginkgo biloba is a dioecious tree and its extract is a complex mixture that has been used for thousands of years to treat a variety of ailments in traditional Chinese medicine. The aim of this study was to present our observations on the inhibitory effects of different Ginkgo biloba extracts on human breast cancer cell proliferation and growth. Our results demonstrated that treatment of MCF-7 and MDA-MB-231 human breast cancer cells with Ginkgo biloba leaves and ginkgo fruit extract inhibited cell proliferation. It was also observed that this inhibition was accompanied by the enhancement of cytochrome P450 (CYP) 1B1 expression in MDA-MB-231 cells. In addition, treatment with ginkgo fruit extract resulted in a higher CYP1B1 expression in MDA-MB-231 cells compared to treatment with the Ginkgo biloba leaves extract. Our results suggested that the inhibitory effects of the Ginkgo biloba extract on estrogen receptor-negative breast cancer proliferation and the induction of CYP1B1 expression may be exerted through an alternative pathway, independent of the estrogen receptor or the aryl hydrocarbon receptor pathway.

  14. The association between the melatonin receptor 1B gene polymorphism rs10830963 and glucose levels in type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Tarek S Heshmat

    2014-01-01

    Conclusion The study confirmed that individuals having the MTNR1B gene polymorphism are at a greater risk of developing type 2 diabetes and having higher blood glucose levels and are more prone to be dyslipidemic than others who have no polymorphism.

  15. Association between the melatonin receptor 1B gene polymorphism on the risk of type 2 diabetes, impaired glucose regulation: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Qing Xia

    Full Text Available BACKGROUND: Melatonin receptor 1B (MTNR1B belongs to the seven-transmembrane G protein-coupled receptor superfamily involved in insulin secretion, which has attracted considerable attention as a candidate gene for type 2 diabetes (T2D since it was first identified as a loci associated with fasting plasma glucose level through genome wide association approach. The relationship between MTNR1B and T2D has been reported in various ethnic groups. The aim of this study was to consolidate and summarize published data on the potential of MTNR1B polymorphisms in T2D risk prediction. METHODS: PubMed, EMBASE, ISI web of science and the CNKI databases were systematically searched to identify relevant studies. Odds ratios (ORs and 95% confidence intervals (95% CIs were calculated. Heterogeneity and publication bias were also tested. RESULTS: A total of 23 studies involving 172,963 subjects for two common polymorphisms (rs10830963, rs1387153 on MTNR1B were included. An overall random effects per-allele OR of 1.05 (95% CI: 1.02-1.08; P<10(-4 and 1.04 (95% CI: 0.98-1.10; P = 0.20 were found for the two variants respectively. Similar results were also observed using dominant or recessive genetic model. There was strong evidence of heterogeneity, which largely disappeared after stratification by ethnicity. Significant results were found in Caucasians when stratified by ethnicity; while no significant associations were observed in East Asians and South Asians. Besides, we found that the rs10830963 polymorphism is a risk factor associated with increased impaired glucose regulation susceptibility. CONCLUSIONS: This meta-analysis demonstrated that the rs10830963 polymorphism is a risk factor for developing impaired glucose regulation and T2D.

  16. Insulin-like growth factor 1 (IGF-1) regulates prolactin, growth hormone, and IGF-1 receptor expression in the pituitary gland of the gilthead sea bream Sparus aurata.

    Science.gov (United States)

    Mohammed-Geba, Khaled; Martos-Sitcha, J A; Galal-Khallaf, A; Mancera, J M; Martínez-Rodríguez, G

    2016-02-01

    The role of insulin-like growth factor 1 (IGF-1) on regulation of growth hormone (GH) and prolactin (PRL) as well as the possible involvement of IGF-1 receptor subtype a (IGF-1Ra) mRNA was assessed in juvenile specimens of Sparus aurata. IGF-1Ra was successfully cloned, and active receptor domains were localized in its mRNA precursor. Also, phylogenetic analysis of the protein sequence indicated a closer proximity to IGF-1Ra isoform found in zebrafish and other teleosts, than to the isoform IGF-1Rb. The most abundant presence of IGF-1Ra mRNA was detected in white muscle, whereas head kidney showed the lowest gene expression among 24 different studied tissues. Pituitaries of juvenile specimens of S. aurata were incubated in vitro with different doses of IGF-1 (0, 1, 100, and 1000 ng mL(-1)) during a period of 10 h. Total RNA with a high quality could be obtained from these pituitaries. PRL mRNA expression significantly increased with increasing IGF-1 doses. Similarly, IGF-1Ra mRNA increased its expression in response to IGF-1. However, GH mRNA levels decreased in a dose-dependent manner after IGF-1 treatment. The contradictory responses of GH and PRL expressions to IGF-1 in our experiment are possibly mediated by IGF-1Ra presence on the somatotrophs and prolactotrophs. The increase in IGF-1Ra mRNA levels may be related to the proper activation of the PI3-K/Akt signal transduction pathways which are normally involved in GH and PRL regulation.

  17. 偏头痛治疗曙光初现5-HT1B/1D受体激动剂的临床应用%Clinical application of 5-HT1B/1D receptor agonist(triptan) to the treatment of migraine--a ray of sunlight

    Institute of Scientific and Technical Information of China (English)

    张石革; 马国辉

    2004-01-01

    OBJECTIVE:Migraine is a common and frequently-occurring disease in neuromedicine.with understading of mechanism of migraine,new anti-migraine drugs have been found constantly to summarize the aspect of clinical application and progress on 5-HT1B/1D receptor agonist(Triptan).METHODS: To collecte medical literatures in recent years at home and abroad.CONCLUSION:Advance in 5-HT1B/1D receptor agonist has been swiftly in recent years, it has higher selectivity to 5-HT1B/1D receptor, contraction of cerebral vessel and arteriae temporalis, efficacy being related to dosage, promoting distribution of blood flow,so 5-HT1B/1D receptor agonist(triptan) plays an important roles in treatment of migraine.

  18. 5-HT1A/1B receptors as targets for optimizing pigmentary responses in C57BL/6 mouse skin to stress.

    Directory of Open Access Journals (Sweden)

    Hua-Li Wu

    Full Text Available Stress has been reported to induce alterations of skin pigmentary response. Acute stress is associated with increased turnover of serotonin (5-hydroxytryptamine; 5-HT whereas chronic stress causes a decrease. 5-HT receptors have been detected in pigment cells, indicating their role in skin pigmentation. To ascertain the precise role of 5-HT in stress-induced pigmentary responses, C57BL/6 mice were subjected to chronic restraint stress and chronic unpredictable mild stress (CRS and CUMS, two models of chronic stress for 21 days, finally resulting in abnormal pigmentary responses. Subsequently, stressed mice were characterized by the absence of a black pigment in dorsal coat. The down-regulation of tyrosinase (TYR and tyrosinase-related proteins (TRP1 and TRP2 expression in stressed skin was accompanied by reduced levels of 5-HT and decreased expression of 5-HT receptor (5-HTR system. In both murine B16F10 melanoma cells and normal human melanocytes (NHMCs, 5-HT had a stimulatory effect on melanin production, dendricity and migration. When treated with 5-HT in cultured hair follicles (HFs, the increased expression of melanogenesis-related genes and the activation of 5-HT1A, 1B and 7 receptors also occurred. The serum obtained from stressed mice showed significantly decreased tyrosinase activity in NHMCs compared to that from nonstressed mice. The decrease in tyrosinase activity was further augmented in the presence of 5-HTR1A, 1B and 7 antagonists, WAY100635, SB216641 and SB269970. In vivo, stressed mice received 5-HT precursor 5-hydroxy-l-tryptophan (5-HTP, a member of the class of selective serotonin reuptake inhibitors (fluoxetine; FX and 5-HTR1A/1B agonists (8-OH-DPAT/CP94253, finally contributing to the normalization of pigmentary responses. Taken together, these data strongly suggest that the serotoninergic system plays an important role in the regulation of stress-induced depigmentation, which can be mediated by 5-HT1A/1B receptors. 5-HT

  19. Association of rs10830963 and rs10830962 SNPs in the melatonin receptor (MTNR1B) gene among Han Chinese women with polycystic ovary syndrome.

    Science.gov (United States)

    Li, Chao; Shi, Yuhua; You, Li; Wang, Laicheng; Chen, Zi-Jiang

    2011-03-01

    The aim of the present study was to determine whether or not the 'melatonin receptor (MTNR1B)' gene polymorphisms are associated with a predisposition for polycystic ovary syndrome (PCOS). The single-nucleotide polymorphisms (SNPs), rs10830963 and rs10830962, in the MTNR1B gene were detected in 526 patients with PCOS and 547 healthy Chinese Han women. The association between MTNR1B gene variants and plasma glucose and insulin levels during the oral glucose tolerance test (OGTT) and hormone levels was investigated. The frequencies of three genotypes and two allelotypes of the SNP, rs10830963, differed significantly between women with PCOS and healthy controls (P insulin resistance (HOMA-IR; P = 0.027). No significant differences were observed in the genotypes and allele distributions of rs10830962 polymorphisms between the PCOS and the control groups (P = 0.311 and P = 0.178, respectively). There was no significant difference in the clinical and the metabolic characteristics in women with PCOS with different genotypes in the SNP, rs10830962 (all P > 0.005). The present study suggest that the SNP, rs10830963, in the MTNR1B gene is not only associated with susceptibility to PCOS, but also contributes to the PCOS phenotype.

  20. An overview of SSR149415, a selective nonpeptide vasopressin V(1b) receptor antagonist for the treatment of stress-related disorders.

    Science.gov (United States)

    Serradeil-Le Gal, Claudine; Wagnon, Jean; Tonnerre, Bernard; Roux, Richard; Garcia, Georges; Griebel, Guy; Aulombard, Alain

    2005-01-01

    Vasopressin (AVP) and corticotropin-releasing factor (CRF) are key mediators in the organism's neuro-adaptive response to stress. Through pituitary and central vasopressin V(1b) receptors, AVP participates in the control of the hypothalamic-pituitary-adrenal axis (HPA) and is involved in various emotional processes. SSR149415 is the first selective, orally active vasopressin V(1b) receptor antagonist yet described. It is a competitive antagonist with nanomolar affinity for animal and human V(1b) receptors and displays a highly selective profile with regard to a large number of receptors or enzymes. In vitro, SSR149415 potently antagonizes functional cellular events associated with V(1b) receptor activation by AVP, such as intracellular Ca(2+) increase or proliferation in various cell systems. Pharmacological studies, performed by measuring ACTH secretion induced by various stimulants such as hormones (AVP or AVP + CRF) or physical stress (restraint or forced swimming stress and dehydration) in conscious rats or mice, confirm the antagonist profile of SSR149415 and its efficacy in normalizing ACTH secretion in vivo. SSR149415 is active by the oral route, at doses from 3 mg/kg, it potentiates CRF effect and displays a long-lasting oral effect in the different models. At 10 mg/kg p.o. its duration of action is longer than 4 h. This molecule also decreases anxiety and exerts marked antidepressant-like activity in several predictive animal models. The anxiolytic effects of SSR149415 have been demonstrated in various Generalized Anxiety Disorders (GAD) models (four-plate, punished drinking, elevated plus-maze, light dark, mouse defense test battery, fear-potentiated startle and social interaction tests). It is as effective as the benzodiazepine diazepam in the acute stress exposure test. SSR149415 has similar efficacy to the reference antidepressant drug, fluoxetine, in acute (forced-swimming) and chronic (chronic mild stress and subordination stress) situations in

  1. A Molecular Case-Control Study on the Association of Melatonin Hormone and rs#10830963 Single Nucleotide Polymorphism in its Receptor MTNR1B Gene with Breast Cancer

    Directory of Open Access Journals (Sweden)

    Nadia A Abd El Moneim

    2015-01-01

    Full Text Available Background: The main function of the pineal hormone melatonin which is mediated via its two receptors, MTNR1A and MTNR1B, is to mediate dark signals in addition to anti-oxidation, immune system enhancement, protection from radiation, and anti-cancer functions. A common single nucleotide polymorphism in the MTNR1B gene is rs#10830963, which is well known as a risk factor for type 2 diabetes mellitus. This study intends to figure out the role of melatonin and its receptor MTNR1B gene rs#10830963 polymorphism in breast cancer incidence, diagnosis and prognosis. Methods: This study included 43 females with breast cancer and 45 apparently normal healthy females. Restriction fragment length polymorphism-PCR was used for amplification and genotyping of the MTNR1B gene rs#10830963 polymorphism in whole blood. Serum melatonin levels were measured using a ready-for-use radioimmunoassay kit. Results: For the MTNR1B gene rs#10830963 polymorphism, we observed a significantly higher GG genotype frequency among cases (72.1% than controls (13.3%, with a diagnostic sensitivity of 83.78% and specificity of 76.47%. The cases had a frequency of 11.6% for the CC genotype and 16.3% for the CG genotype which was significantly lower compared to controls that had a 44.4% frequency of the CC genotype and 42.2% frequency of the CG genotype. The GG genotype had a significant association with larger tumor volume (P=0.048. Serum melatonin levels were significantly lower among breast cancer patients than controls. Using the ROC curve analysis, serum melatonin showed a significant AUC (72.6%, P39.5 pg/ml. Conclusion: The risk for breast cancer incidence increased as the serum levels of melatonin decreased and in females homozygous for the G allele (GG genotype of the MTNR1B gene rs#10830963 polymorphism. The GG genotype was found to be associated with increased breast tumor volume as a marker of a poor prognosis breast cancer.

  2. MAP1B binds to the NMDA receptor subunit NR3A and affects NR3A protein concentrations

    DEFF Research Database (Denmark)

    Eriksson, Maria; Samuelsson, Helena; Björklund, Stefan;

    2010-01-01

    Incorporation of the N-methyl-d-aspartate receptor (NMDAR) subunit NR3A into functional NMDARs results in reduced channel conductance and Ca(2+) permeability. To further investigate the function of NR3A, we have set out to characterize its intracellular binding partners. Here, we report a novel p...

  3. Serotonergic modulation of neurotransmission in the rat subicular cortex in vitro: A role for 5-HT(1B) receptors

    NARCIS (Netherlands)

    Boeijinga, P.H.; Boddeke, H.W.G.M.

    1993-01-01

    We have studied the effect of serotonin on synaptic transmission in rat hippocampal subiculum slices. Electrical stimulation of the alveus induced a field potential in the subiculum. The non-NMDA glutamate receptor antagonist, NBQX (3 x 10-6mol/l) suppressed the response by 78%, indicating that the

  4. SEROTONERGIC MODULATION OF NEUROTRANSMISSION IN THE RAT SUBICULAR CORTEX IN-VITRO - A ROLE FOR 5-HT(1B) RECEPTORS

    NARCIS (Netherlands)

    BOEIJINGA, PH; BODDEKE, HWGM

    1993-01-01

    We have studied the effect of serotonin on synaptic transmission in rat hippocampal subiculum slices. Electrical stimulation of the alveus induced a field potential in the subiculum. The non-NMDA glutamate receptor antagonist, NBQX (3 x 10(-6) mol/l) suppressed the response by 78%, indicating that t

  5. The Nogo-C2/Nogo receptor complex regulates the morphogenesis of zebrafish lateral line primordium through modulating the expression of dkk1b, a Wnt signal inhibitor.

    Directory of Open Access Journals (Sweden)

    Hao-Wei Han

    Full Text Available The fish lateral line (LL is a mechanosensory system closely related to the hearing system of higher vertebrates, and it is composed of several neuromasts located on the surface of the fish. These neuromasts can detect changes in external water flow, to assist fish in maintaining a stationary position in a stream. In the present study, we identified a novel function of Nogo/Nogo receptor signaling in the formation of zebrafish neuromasts. Nogo signaling in zebrafish, like that in mammals, involves three ligands and four receptors, as well as three co-receptors (TROY, p75, and LINGO-1. We first demonstrated that Nogo-C2, NgRH1a, p75, and TROY are able to form a Nogo-C2 complex, and that disintegration of this complex causes defective neuromast formation in zebrafish. Time-lapse recording of the CldnB::lynEGFP transgenic line revealed that functional obstruction of the Nogo-C2 complex causes disordered morphogenesis, and reduces rosette formation in the posterior LL (PLL primordium during migration. Consistent with these findings, hair-cell progenitors were lost from the PLL primordium in p75, TROY, and Nogo-C2/NgRH1a morphants. Notably, the expression levels of pea3, a downstream marker of Fgf signaling, and dkk1b, a Wnt signaling inhibitor, were both decreased in p75, TROY, and Nogo-C2/NgRH1a morphants; moreover, dkk1b mRNA injection could rescue the defects in neuromast formation resulting from knockdown of p75 or TROY. We thus suggest that a novel Nogo-C2 complex, consisting of Nogo-C2, NgRH1a, p75, and TROY, regulates Fgf signaling and dkk1b expression, thereby ensuring stable organization of the PLL primordium.

  6. Xenoestrogens at picomolar to nanomolar concentrations trigger membrane estrogen receptor-alpha-mediated Ca2+ fluxes and prolactin release in GH3/B6 pituitary tumor cells.

    Science.gov (United States)

    Wozniak, Ann L; Bulayeva, Nataliya N; Watson, Cheryl S

    2005-04-01

    Xenoestrogens (XEs) are widespread in our environment and are known to have deleterious effects in animal (and perhaps human) populations. Acting as inappropriate estrogens, XEs are thought to interfere with endogenous estrogens such as estradiol (E2) to disrupt normal estrogenic signaling. We investigated the effects of E2 versus several XEs representing organochlorine pesticides (dieldrin, endosulfan, o',p'-dichlorodiphenylethylene), plastics manufacturing by-products/detergents (nonylphenol, bisphenol A), a phytoestrogen (coumestrol), and a synthetic estrogen (diethylstilbestrol) on the pituitary tumor cell subline GH3/B6/F10, previously selected for expression of high levels of membrane estrogen receptor-alpha. Picomolar to nanomolar concentrations of both E2 and XEs caused intracellular Ca2+ changes within 30 sec of administration. Each XE produced a unique temporal pattern of Ca2+ elevation. Removing Ca2+ from the extracellular solution abolished both spontaneous and XE-induced intracellular Ca2+ changes, as did 10 microM nifedipine. This suggests that XEs mediate their actions via voltage-dependent L-type Ca2+ channels in the plasma membrane. None of the Ca2+ fluxes came from intracellular Ca2+ stores. E2 and each XE also caused unique time- and concentration-dependent patterns of prolactin (PRL) secretion that were largely complete within 3 min of administration. PRL secretion was also blocked by nifedipine, demonstrating a correlation between Ca2+ influx and PRL secretion. These data indicate that at very low concentrations, XEs mediate membrane-initiated intracellular CCa2+ increases resulting in PRL secretion via a mechanism similar to that for E2, but with distinct patterns and potencies that could explain their abilities to disrupt endocrine functions.

  7. The inhibitory effect of combination treatment with leptin and cannabinoid CB1 receptor agonist on food intake and body weight gain is mediated by serotonin 1B and 2C receptors.

    Science.gov (United States)

    Wierucka-Rybak, M; Wolak, M; Juszczak, M; Drobnik, J; Bojanowska, E

    2016-06-01

    Previous studies reported that the co-injection of leptin and cannabinoid CB1 receptor antagonists reduces food intake and body weight in rats, and this effect is more profound than that induced by these compounds individually. Additionally, serotonin mediates the effects of numerous anorectic drugs. To investigate whether serotonin interacts with leptin and endocannabinoids to affect food intake and body weight, we administered 5-hydroxytryptamine(HT)1B and 5-hydroxytryptamine(HT)2C serotonin receptor antagonists (3 mg/kg GR 127935 and 0.5 mg/kg SB 242084, respectively) to male Wistar rats treated simultaneously with leptin (100 μg/kg) and the CB1 receptor inverse agonist AM 251 (1 mg/kg) for 3 days. In accordance with previous findings, the co-injection of leptin and AM 251, but not the individual injection of each drug, resulted in a significant decrease in food intake and body weight gain. Blockade of the 5-HT1B and 5-HT2C receptors completely abolished the leptin- and AM 251-induced anorectic and body-weight-reducing effects. These results suggest that serotonin mediates the leptin- and AM 251-dependent regulation of feeding behavior in rats via the 5-HT1B and 5-HT2C receptors.

  8. Prolactin levels and adverse events in patients treated with risperidone.

    Science.gov (United States)

    Kleinberg, D L; Davis, J M; de Coster, R; Van Baelen, B; Brecher, M

    1999-02-01

    Hyperprolactinemia is a common clinical disorder that may lead to sexual dysfunction or galactorrhea. It may arise from a variety of etiologies, including the use of antipsychotic agents, presumably because of a dopamine receptor blockade. This analysis was designed to characterize the relationship between risperidone, serum prolactin levels, and possible clinical sequelae. All data from randomized, double-blind studies of risperidone in patients with chronic schizophrenia were analyzed. The two largest studies (the North American and multinational trials) included 841 patients (259 women, 582 men) with paired prolactin level data and 1,884 patients (554 women, 1,330 men) with data on six adverse events possibly associated with increased prolactin levels (amenorrhea, galactorrhea, and decreased libido in women; erectile dysfunction, ejaculatory dysfunction, gynecomastia, and decreased libido in men). Both risperidone and haloperidol produced dose-related increases in plasma prolactin levels in men and women. Among women, the risperidone dose was not correlated with adverse events, nor were the adverse events correlated with endpoint prolactin levels. Among men, the incidence of adverse events was positively correlated with risperidone dose; however, at risperidone doses of 4 to 10 mg/day the incidence of adverse events was not significantly higher than that observed in patients receiving placebo. Furthermore, adverse events in men were unrelated to plasma prolactin levels. Risperidone-associated increase in serum prolactin levels was not significantly correlated to the emergence of possible prolactin-related side effects.

  9. Prophylactic effects of asiaticoside-based standardized extract of Centella asiatica (L.) Urban leaves on experimental migraine: Involvement of 5HT1A/1B receptors.

    Science.gov (United States)

    Bobade, Vijeta; Bodhankar, Subhash L; Aswar, Urmila; Vishwaraman, Mohan; Thakurdesai, Prasad

    2015-04-01

    The present study aimed at evaluation of prophylactic efficacy and possible mechanisms of asiaticoside (AS) based standardized extract of Centella asiatica (L.) Urban leaves (INDCA) in animal models of migraine. The effects of oral and intranasal (i.n.) pretreatment of INDCA (acute and 7-days subacute) were evaluated against nitroglycerine (NTG, 10 mg·kg(-1), i.p.) and bradykinin (BK, 10 μg, intra-arterial) induced hyperalgesia in rats. Tail flick latencies (from 0 to 240 min) post-NTG treatment and the number of vocalizations post-BK treatment were recorded as a measure of hyperalgesia. Separate groups of rats for negative (Normal) and positive (sumatriptan, 42 mg·kg(-1), s.c.) controls were included. The interaction of INDCA with selective 5-HT1A, 5-HT1B, and 5-HT1D receptor antagonists (NAN-190, Isamoltane hemifumarate, and BRL-15572 respectively) against NTG-induced hyperalgesia was also evaluated. Acute and sub-acute pre-treatment of INDCA [10 and 30 mg·kg(-1) (oral) and 100 μg/rat (i.n.) showed significant anti-nociception activity, and reversal of the NTG-induced hyperalgesia and brain 5-HT concentration decline. Oral pre-treatment with INDCA (30 mg·kg(-1), 7 d) showed significant reduction in the number of vocalization. The anti-nociceptive effects of INDCA were blocked by 5-HT1A and 5-HT1B but not 5-HT1D receptor antagonists. In conclusion, INDCA demonstrated promising anti-nociceptive effects in animal models of migraine, probably through 5-HT1A/1B medicated action.

  10. mRNA expression of 5-hydroxytryptamine 1B, 1D, and 1F receptors and their role in controlling the release of calcitonin gene-related peptide in the rat trigeminovascular system

    DEFF Research Database (Denmark)

    Amrutkar, Dipak V; Ploug, Kenneth B; Hay-Schmidt, Anders;

    2012-01-01

    Triptans, a family of 5-hydroxytryptamine (5-HT) 1B, 1D, and 1F receptor agonists, are used in the acute treatment of migraine attacks. The site of action and subtypes of the 5-HT(1) receptor that mediate the antimigraine effect have still to be identified. This study investigated the mRNA expres......Triptans, a family of 5-hydroxytryptamine (5-HT) 1B, 1D, and 1F receptor agonists, are used in the acute treatment of migraine attacks. The site of action and subtypes of the 5-HT(1) receptor that mediate the antimigraine effect have still to be identified. This study investigated the m...

  11. Pharmacological characterization of homobaclofen on wild type and mutant GABA(B)1b receptors coexpressed with the GABA(B)2 receptor

    DEFF Research Database (Denmark)

    Jensen, Anders A.; Madsen, Bo E.; Krogsgaard-Larsen, P;

    2001-01-01

    Homobaclofen (5-amino-3-(4-chlorophenyl) pentanoic acid) is a homologue of the classical GABA(B) receptor agonist baclofen. In a recent study, the two enantiomers of this compound were tested in a GABA(B) receptor selective [3H]gamma-aminobutyric acid ([3H]GABA) binding assay using rat brain homo...

  12. Stress-induced release of anterior pituitary hormones: Effect of H3 receptor-mediated inhibition of histaminergic activity or posterior hypothalamic lesion

    DEFF Research Database (Denmark)

    Knigge, U.; Søe-Jensen, P.; Jørgensen, Henrik;

    1999-01-01

    Histamine receptors, corticotropin, *Gb-endorphin, prolactin, adrenal steroids, stress, endotoxin, serotonin......Histamine receptors, corticotropin, *Gb-endorphin, prolactin, adrenal steroids, stress, endotoxin, serotonin...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1987-03-02

    In the present study, the ability of three direct GABA agonists, muscimol, THIP and SL 76002 to displace /sup 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 /sup 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 /sup 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 /sup 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.

  14. Test-retest reliability of the novel 5-HT{sub 1B} receptor PET radioligand [{sup 11}C]P943

    Energy Technology Data Exchange (ETDEWEB)

    Saricicek, Aybala [Yale University, Department of Psychiatry, New Haven, CT (United States); Connecticut Mental Health Center, Abraham Ribicoff Research Facilities, New Haven, CT (United States); Izmir Katip Celebi University, Department of Psychiatry, Izmir (Turkey); Chen, Jason; Ruf, Barbara [Yale University, Department of Psychiatry, New Haven, CT (United States); Planeta, Beata; Labaree, David; Gallezot, Jean-Dominique; Huang, Yiyun [Yale University, PET Center, Department of Diagnostic Radiology, New Haven, CT (United States); Subramanyam, Kalyani; Maloney, Kathleen [Yale University, Department of Psychiatry, New Haven, CT (United States); Connecticut Mental Health Center, Abraham Ribicoff Research Facilities, New Haven, CT (United States); Matuskey, David [Yale University, Department of Psychiatry, New Haven, CT (United States); Connecticut Mental Health Center, Abraham Ribicoff Research Facilities, New Haven, CT (United States); Yale University, PET Center, Department of Diagnostic Radiology, New Haven, CT (United States); Deserno, Lorenz [Charite - Universitaetsmedizin Berlin, Department of Psychiatry and Psychotherapy, Campus Charite Mitte, Berlin (Germany); Max-Planck-Institute for Human Cognitive and Brain Sciences, Leipzig, Berlin (Germany); Neumeister, Alexander [Yale University, Department of Psychiatry, New Haven, CT (United States); Mount Sinai School of Medicine, Department of Psychiatry, New York, NY (United States); VA Connecticut Healthcare System, Clinical Neuroscience Division, VA National Center for PTSD, West Haven, CT (United States); Krystal, John H. [Yale University, Department of Psychiatry, New Haven, CT (United States); Connecticut Mental Health Center, Abraham Ribicoff Research Facilities, New Haven, CT (United States); VA Connecticut Healthcare System, Clinical Neuroscience Division, VA National Center for PTSD, West Haven, CT (United States); Carson, Richard E. [Connecticut Mental Health Center, Abraham Ribicoff Research Facilities, New Haven, CT (United States); Bhagwagar, Zubin [Yale University, Department of Psychiatry, New Haven, CT (United States); Connecticut Mental Health Center, Abraham Ribicoff Research Facilities, New Haven, CT (United States); Bristol-Myers Squibb, Wallingford, CT (United States)

    2014-11-27

    [{sup 11}C]P943 is a novel, highly selective 5-HT{sub 1B} PET radioligand. The aim of this study was to determine the test-retest reliability of [{sup 11}C]P943 using two different modeling methods and to perform a power analysis with each quantification technique. Seven healthy volunteers underwent two PET scans on the same day. Regions of interest (ROIs) were the amygdala, hippocampus, pallidum, putamen, insula, frontal, anterior cingulate, parietal, temporal and occipital cortices, and cerebellum. Two multilinear radioligand quantification techniques were used to estimate binding potential: MA1, using arterial input function data, and the second version of the multilinear reference tissue model analysis (MRTM2), using the cerebellum as the reference region. Between-scan percent variability and intraclass correlation coefficients (ICC) were used to assess test-retest reliability. We also performed power analyses to determine the method that would allow the least number of subjects using within-subject or between-subject study designs. A voxel-wise ICC analysis for MRTM2 BP{sub ND} was performed for the whole brain and all the ROIs studied. Mean percent variability between two scans across regions ranged between 0.4 % and 12.4 % for MA1 BP{sub ND}, 0.5 % and 11.5 % for MA1 BP{sub P}, 16.7 % and 28.3 % for MA1 BP{sub F}, and between 0.2 % and 5.4 % for MRTM2 BP{sub ND}. The power analyses showed a greater number of subjects were required using MA1 BP{sub F} compared with other outcome measures for both within-subject and between-subject study designs. ICC values were the highest using MRTM2 BP{sub ND} and the lowest with MA1 BP{sub F} in ten ROIs. Small regions and regions with low binding had lower ICC values than large regions and regions with high binding. Reliable measures of 5-HT{sub 1B} receptor binding can be obtained using the novel PET radioligand [{sup 11}C]P943. Quantification of 5-HT{sub 1B} receptor binding with MRTM2 BP{sub ND} and with MA1 BP{sub P

  15. The relevance of preclinical research models for the development of antimigraine drugs: focus on 5-HT(1B/1D) and CGRP receptors.

    Science.gov (United States)

    Gupta, Saurabh; Villalón, Carlos M

    2010-10-01

    Migraine is a complex neurovascular syndrome, causing a unilateral pulsating headache with accompanying symptoms. The past four decades have contributed immensely to our present understanding of migraine pathophysiology and have led to the introduction of specific antimigraine therapies, much to the relief of migraineurs. Pathophysiological factors culminating into migraine headaches have not yet been completely deciphered and, thus, pose an additional challenge for preclinical research in the absence of any direct experimental marker. Migraine provocation experiments in humans use a head-score to evaluate migraine, as articulated by the volunteer, which cannot be applied to laboratory animals. Therefore, basic research focuses on different symptoms and putative mechanisms, one at a time or in combination, to validate the hypotheses. Studies in several species, utilizing different preclinical approaches, have significantly contributed to the two antimigraine principles in therapeutics, namely: 5-HT(1B/1D) receptor agonists (known as triptans) and CGRP receptor antagonists (known as gepants). This review will analyze the preclinical experimental models currently known for the development of these therapeutic principles, which are mainly based on the vascular and/or neurogenic theories of migraine pathogenesis. These include models based on the involvement of cranial vasodilatation and/or the trigeminovascular system in migraine. Clearly, the preclinical strategies should involve both approaches, while incorporating the newer ideas/techniques in order to get better insights into migraine pathophysiology.

  16. Recent Research Advances in Receptor of Prolactin Releasing Peptide%催乳素释放肽受体的研究进展

    Institute of Scientific and Technical Information of China (English)

    陈宇; 朱河水

    2009-01-01

    催乳素释放肽(Prolactin Releasing Peptide,PrRP)是一种RF肽,催乳素释放肽受体(PrRP-R)为G蛋白偶联受体(GPCR).综述了PrRP-R基因特点以及PrRP-R在体内的分布、表达以及亲和性等.

  17. Hyperprolactinemia (Prolactin Excess)

    Science.gov (United States)

    ... When men or women who are not pregnant produce breast milk. Hypothyroidism : Underactive thyroid. Pituitary : A walnut-sized gland that sits at the bottom of the brain and releases hormones related to reproduction and growth. Prolactin inhibiting factor (PIF): A hormone that stops ...

  18. Gestational chronodisruption impairs hippocampal expression of NMDA receptor subunits Grin1b/Grin3a and spatial memory in the adult offspring.

    Directory of Open Access Journals (Sweden)

    Nelson Vilches

    Full Text Available Epidemiological and experimental evidence correlates adverse intrauterine conditions with the onset of disease later in life. For a fetus to achieve a successful transition to extrauterine life, a myriad of temporally integrated humoral/biophysical signals must be accurately provided by the mother. We and others have shown the existence of daily rhythms in the fetus, with peripheral clocks being entrained by maternal cues, such as transplacental melatonin signaling. Among developing tissues, the fetal hippocampus is a key structure for learning and memory processing that may be anticipated as a sensitive target of gestational chronodisruption. Here, we used pregnant rats exposed to constant light treated with or without melatonin as a model of gestational chronodisruption, to investigate effects on the putative fetal hippocampus clock, as well as on adult offspring's rhythms, endocrine and spatial memory outcomes. The hippocampus of fetuses gestated under light:dark photoperiod (12:12 LD displayed daily oscillatory expression of the clock genes Bmal1 and Per2, clock-controlled genes Mtnr1b, Slc2a4, Nr3c1 and NMDA receptor subunits 1B-3A-3B. In contrast, in the hippocampus of fetuses gestated under constant light (LL, these oscillations were suppressed. In the adult LL offspring (reared in LD during postpartum, we observed complete lack of day/night differences in plasma melatonin and decreased day/night differences in plasma corticosterone. In the adult LL offspring, overall hippocampal day/night difference of gene expression was decreased, which was accompanied by a significant deficit of spatial memory. Notably, maternal melatonin replacement to dams subjected to gestational chronodisruption prevented the effects observed in both, LL fetuses and adult LL offspring. Collectively, the present data point to adverse effects of gestational chronodisruption on long-term cognitive function; raising challenging questions about the consequences of

  19. Glucocorticoid receptor 1B and 1C mRNA transcript alterations in schizophrenia and bipolar disorder, and their possible regulation by GR gene variants.

    Directory of Open Access Journals (Sweden)

    Duncan Sinclair

    Full Text Available Abnormal patterns of HPA axis activation, under basal conditions and in response to stress, are found in individuals with schizophrenia and bipolar disorder. Altered glucocorticoid receptor (GR mRNA and protein expression in the dorsolateral prefrontal cortex (DLPFC in psychiatric illness have also been reported, but the cause of these abnormalities is not known. We quantified expression of GR mRNA transcript variants which employ different 5' promoters, in 35 schizophrenia cases, 31 bipolar disorder cases and 34 controls. We also explored whether sequence variation within the NR3C1 (GR gene is related to GR mRNA variant expression. Total GR mRNA was decreased in the DLPFC in schizophrenia cases relative to controls (15.1%, p<0.0005 and also relative to bipolar disorder cases (8.9%, p<0.05. GR-1B mRNA was decreased in schizophrenia cases relative to controls (20.2%, p<0.05, while GR-1C mRNA was decreased in both schizophrenia and bipolar disorder cases relative to controls (16.1% and 17.2% respectively, both p<0.005. A dose-dependent effect of rs10052957 genotype on GR-1B mRNA expression was observed, where CC homozygotes displayed 18.4% lower expression than TC heterozygotes (p<0.05, and 31.8% lower expression than TT homozygotes (p<0.005. Similarly, a relationship between rs6190 (R23K genotype and GR-1C expression was seen, with 24.8% lower expression in GG homozygotes than GA heterozygotes (p<0.01. We also observed an effect of rs41423247 (Bcl1 SNP on expression of 67 kDa GRα isoform, the most abundant GRα isoform in the DLPFC. These findings suggest possible roles for the GR-1B and GR-1C promoter regions in mediating GR gene expression changes in psychotic illness, and highlight the potential importance of sequence variation within the NR3C1 gene in modulating GR mRNA expression in the DLPFC.

  20. Improvement in neurological outcome and abolition of cerebrovascular endothelin B and 5-hydroxytryptamine 1B receptor upregulation through mitogen-activated protein kinase kinase 1/2 inhibition after subarachnoid hemorrhage in rats

    DEFF Research Database (Denmark)

    Larsen, Carl Christian; Povlsen, Gro Klitgaard; Rasmussen, Marianne Nelly Paola;

    2011-01-01

    )) and 5-hydroxytryptamine 1B (5-HT(1B)) receptors has been demonstrated in cerebral artery smooth muscles in the delayed ischemic phase after experimental SAH, and intracellular signaling via the mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase 1/2 pathway has been shown......Delayed cerebral ischemia after subarachnoid hemorrhage (SAH) remains a major cause of death and disability. It has been hypothesized that cerebrovascular upregulation of vasoconstrictor receptors is a key step in the development of delayed cerebral ischemia. Upregulation of endothelin-B (ET(B...

  1. Preparation of polycolonal antibody against goose prolactin receptor and the receptor expression in goose tissues%鹅催乳素受体多克隆抗体制备及组织表达分析

    Institute of Scientific and Technical Information of China (English)

    邢光东; 杨廷桂; 段修军; 宦海琳; 闫俊书; 王根林

    2011-01-01

    To study the functions of prolactin receptor( PRLR) in goose,we constructed a prokaryotic expression vector exPRLR-Pet-28a( +) that contains exPRLR, the coding sequences of the whole extracellular domain of goose PRLR. Transformed into host bacteria E. Coli Roster and induced by IPTG,ex:PRLR-Pet-28a( +)expressed recombinant protein exPRLR. By immunizing rabbit with the re-combinant protein, we obtained rabbit anti-goose exPRLR polycolonal serum. Western blot assay revealed that the anti-serum recognized the recombinant protein expressed by the transformed bacteria specifically. Analyzing the proteins isolated from adult female goose tissues with the anti-serum, we found that adult geese might have at least three isoforms of PRLR with different relative molecular mass.%为深入研究鹅催乳素受体(PRLR)的功能,构建了含鹅PRLR胞外域编码序列exPRLR的原核表达质粒exPRLR-pET-28a(+),通过转化E coli Roster建立了稳定的原核表达系统,在IPTG诱导下获得了PRLR胞外域的重组exPRLR.以重组exPRLR为抗原免疫家兔,获得了兔抗鹅exPRLR的抗血清.Western blot分析证明该抗血清可特异识别由原核生物表达的重组exPRLR.进一步分析成年母鹅的组织蛋白,发现成年鹅中可能至少存在3种相对分子质量不同的PRLR蛋白异形体.

  2. Aryl hydrocarbon receptor-dependent upregulation of Cyp1b1 by TCDD and diesel exhaust particles in rat brain microvessels

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    Jacob Aude

    2011-08-01

    Full Text Available Abstract Background AhR activates the transcription of several target genes including CYP1B1. Recently, we showed CYP1B1 as the major cytochrome P450 (CYP enzyme expressed in human brain microvessels. Here, we studied the effect of AhR activation by environmental pollutants on the expression of Cyp1b1 in rat brain microvessels. Methods Expression of AhR and Cyp1b1 was detected in isolated rat brain microvessels. AhR was immunovisualised in brain microvessel endothelial cells. The effect of AhR ligands on Cyp1b1 expression was studied using isolated brain microvessels after ex vivo and/or in vivo exposure to TCDD, heavy hydrocarbons containing diesel exhaust particles (DEP or Δ9-tetrahydrocannabinol (Δ9-THC. Results After ex vivo exposure to TCDD (a highly potent AhR ligand for 3 h, Cyp1b1 expression was significantly increased by 2.3-fold in brain microvessels. A single i.p. dose of TCDD also increased Cyp1b1 transcripts (22-fold and Cyp1b1 protein (2-fold in rat brain microvessels at 72 h after TCDD. Likewise, DEP treatment (in vivo and ex vivo strongly induced Cyp1b1 protein in brain microvessels. DEP-mediated Cyp1b1 induction was inhibited by actinomycin D, cycloheximide, or by an AhR antagonist. In contrast, a sub-chronic in vivo treatment with Δ9-THC once daily for 7 seven days had no effect on Cyp1b1 expression Conclusions Our results show that TCDD and DEP strongly induced Cyp1b1 in rat brain microvessels, likely through AhR activation.

  3. 桥本甲状腺炎患者外周血单个核细胞上催乳素受体mRNA的表达%Expression of prolactin receptor messenger ribonucleic acid on peripheral blood mononuclear cells in patients with Hashimoto's thyroiditis

    Institute of Scientific and Technical Information of China (English)

    孔艳华; 任安; 杨静; 陈若平; 荆春艳; 陈燕; 郑海兰; 王艳燕

    2013-01-01

    探讨催乳素及其受体在桥本甲状腺炎发病机制中的作用.选取新诊断桥本甲状腺炎甲状腺功能正常者33例,正常对照者32名,用荧光实时定量PCR定量检测催乳素受体mRNA,化学发光法测定血清催乳素,酶联免疫法检测白细胞介素2.与对照组相比,桥本甲状腺炎组患者外周血单个核细胞上催乳素受体mRNA含量、催乳素及白细胞介素2水平明显增高[1.190±0.913对0.149±0.130,(13.941±7.109对11.022±3.461)ng/ml,(102.165±43.716对81.862±32.128)pg/ml,P<0.05],提示催乳素可能通过与其受体结合参与人体免疫反应,影响细胞因子的表达,参与桥本甲状腺炎的发生发展.%[Summary] To investigate the role played by serum prolactin and prolactin receptor in the pathogenesis of Hashimoto's thyroiditis(HT).33 newly diagnosed patients with HT with euthyroidism and 32 healthy subjects were enrolled as HT group and normal control group respectively.The expression of prolactin receptor mRNA on peripheral blood mononuclear cells (PBMC) were detected by realtime fluorescence quantitative PCR,serum prolactin was determinated by immunochemiluminescence assay and interleukin 2 was detected by Enzyme-linked immunosorbent.Compared with the controls,the level of prolactin receptor mRNA on PBMC,serum prolactin,interleukin 2 in HT patients were significantly higher[1.190 ± 0.913 vs 0.149 ± 0.130,(13.941 ± 7.109 vs 11.022 ±3.461)ng/ml,(102.165 ±43.716 vs 81.862 ± 32.128) pg/ml,P<0.05] ; it implies that prolactin may be involved in the body's immune defences through combing with its receptor,promoting the activation of lymphocytes,and participating in the development of Hashimoto's thyroiditis.

  4. Characterization of Δ7/11, a functional prolactin-binding protein

    Science.gov (United States)

    Fleming, JM; Ginsburg, E; McAndrew, CW; Heger, CD; Cheston, L; Rodriguez-Canales, J; Vonderhaar, BK; Goldsmith, P

    2012-01-01

    Prolactin is essential for normal mammary gland development and differentiation, and has been shown to promote tumor cell proliferation and chemotherapeutic resistance. Soluble isoforms of the prolactin receptor have been reported to regulate prolactin bioavailability by functioning as “prolactin binding proteins.” Included in this category is Δ7/11, a product of alternate splicing of the prolactin receptor primary transcript. However, the direct interactions of prolactin withΔ7/11, and the resulting effect on cell behavior, have not been investigated. Herein, we demonstrate the ability of Δ7/11 to bind prolactin using a novel proximity ligation assay and traditional immunoprecipitation techniques. Biochemical analyses demonstrated that Δ7/11 was heavily glycosylated, similar to the extracellular domain of the primary prolactin receptor, and that glycosylation regulated the cellular localization and secretion of Δ7/11. Low levels of Δ7/11 were detected in serum samples of healthy volunteers, but were undetectable in human milk samples. Expression of Δ7/11 was also detected in six of the 62 primary breast tumor biopsies analyzed; however, no correlation was found with Δ7/11 expression and tumor histotype or other patient demographics. Functional analysis demonstrated the ability of Δ7/11 to inhibit prolactin-induced cell proliferation as well as alter prolactin-induced rescue of cell cycle arrest/early senescence events in breast epithelial cells. Collectively, these data demonstrate that Δ7/11 is a novel regulatory mechanism of prolactin bioavailability and signaling. PMID:23048206

  5. Effects of 5-HT1B/1D receptor agonist rizatriptan on cerebral blood flow and blood volume in normal circulation.

    Science.gov (United States)

    Okazawa, Hidehiko; Tsuchida, Tatsuro; Pagani, Marco; Mori, Tetsuya; Kobayashi, Masato; Tanaka, Fumiko; Yonekura, Yoshiharu

    2006-01-01

    To investigate the vasoconstrictor effect of 5-hydroxytryptamine (5-HT1B/1D) receptor agonists for migraine treatment, changes in cerebral blood flow (CBF) and blood volume induced by rizatriptan were assessed by positron emission tomography (PET). Eleven healthy volunteers underwent PET studies before and after rizatriptan administration. Dynamic PET data were acquired after bolus injection of H2(15)O to analyze CBF and arterial-to-capillary blood volume (V0) images using the three-weighted integral method. After a baseline scan, three further acquisitions were performed at 40 to 50, 60 and 70 to 80 mins after drug administration. Global and regional differences in CBF and V0 between conditions were compared using absolute values in the whole brain and cortical regions, as well as statistical parametric mapping (SPM) analysis. The global and regional values for CBF and V0 decreased significantly after rizatriptan administration compared with the baseline condition. However, both values recovered to baseline within 80 mins after treatment. The maximal reduction in global CBF and V0 was approximately 13% of baseline value. The greatest decrease in CBF was observed approximately 60 mins after drug administration, whereas the maximal reduction in V0 was observed approximately 5 mins earlier. Statistical parametric mapping did not highlight any regional differences between conditions. Thus, in brain circulation, rizatriptan caused significant CBF and V0 decreases, which are consistent with the vasoconstrictor effect of triptans on the large cerebral arteries. The gradual recovery in the late phase from the maximal CBF and V0 decrease suggests that rizatriptan does not affect the cerebral autoregulatory response in small arteries induced by CBF reduction.

  6. Test-retest reliability of [{sup 11}C]AZ10419369 binding to 5-HT{sub 1B} receptors in human brain

    Energy Technology Data Exchange (ETDEWEB)

    Nord, Magdalena; Finnema, Sjoerd J.; Schain, Martin; Halldin, Christer; Farde, Lars [Karolinska Institutet, Center for Psychiatric Research, R5:00, Karolinska University Hospital, Department of Clinical Neuroscience, Stockholm (Sweden)

    2014-02-15

    [{sup 11}C]AZ10419369 is a recently developed 5-HT{sub 1B} receptor radioligand that is sensitive to changes in endogenous serotonin concentrations in the primate brain. Thus, [{sup 11}C] AZ10419369 may serve as a useful tool in clinical studies of the pathophysiology and pharmacological treatment of diseases related to the serotonin system, such as depression and anxiety disorders. The aim of this study was to evaluate the test-retest reliability of [{sup 11}C]AZ10419369. Eight men were examined with PET and [{sup 11}C] AZ10419369 twice on the same day. The binding potentials (BP{sub ND}) of [{sup 11}C]AZ10419369 in selected serotonergic projection areas and in the raphe nuclei (RN) were determined using the simplified reference tissue model, and for comparison also using a wavelet-aided parametric imaging approach. The BP{sub ND} values obtained from the first and second PET scans were compared by means of descriptive statistics, difference, absolute variability and intraclass correlation coefficient. Similar BP{sub ND} values were obtained with the two methods. The absolute mean differences in BP{sub ND} between PET 1 and PET 2 were less than 3 % in all serotonergic projection regions. Absolute variabilities were low in cortical regions (5 - 7 %), low to moderate (7 - 14 %) in subcortical regions, but higher (20 %) in the RN. The BP{sub ND} of [{sup 11}C]AZ10419369 is highly reproducible in cortical regions and satisfactory in subcortical projection areas. The variability in the RN is higher. Thus larger sample sizes or larger divergences are required to assess a potential difference between subjects or between experimental conditions in this region. (orig.)

  7. Skatole (3-Methylindole Is a Partial Aryl Hydrocarbon Receptor Agonist and Induces CYP1A1/2 and CYP1B1 Expression in Primary Human Hepatocytes.

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    Martin Krøyer Rasmussen

    Full Text Available Skatole (3-methylindole is a product of bacterial fermentation of tryptophan in the intestine. A significant amount of skatole can also be inhaled during cigarette smoking. Skatole is a pulmonary toxin that induces the expression of aryl hydrocarbon receptor (AhR regulated genes, such as cytochrome P450 1A1 (CYP1A1, in human bronchial cells. The liver has a high metabolic capacity for skatole and is the first organ encountered by the absorbed skatole; however, the effect of skatole in the liver is unknown. Therefore, we investigated the impact of skatole on hepatic AhR activity and AhR-regulated gene expression. Using reporter gene assays, we showed that skatole activates AhR and that this is accompanied by an increase of CYP1A1, CYP1A2 and CYP1B1 expression in HepG2-C3 and primary human hepatocytes. Specific AhR antagonists and siRNA-mediated AhR silencing demonstrated that skatole-induced CYP1A1 expression is dependent on AhR activation. The effect of skatole was reduced by blocking intrinsic cytochrome P450 activity and indole-3-carbinole, a known skatole metabolite, was a more potent inducer than skatole. Finally, skatole could reduce TCDD-induced CYP1A1 expression, suggesting that skatole is a partial AhR agonist. In conclusion, our findings suggest that skatole and its metabolites affect liver homeostasis by modulating the AhR pathway.

  8. Aldose reductase (AKR1B3) regulates the accumulation of advanced glycosylation end products (AGEs) and the expression of AGE receptor (RAGE).

    Science.gov (United States)

    Baba, Shahid P; Hellmann, Jason; Srivastava, Sanjay; Bhatnagar, Aruni

    2011-05-30

    Diabetes results in enhanced chemical modification of proteins by advanced lipoxidation end products (ALEs) and advanced glycation end products (AGEs) precursors. These modifications have been linked to the development of several secondary diabetic complications. Our previous studies showed that aldose reductase (AR; AKR1B3) catalyzes the reduction of ALEs and AGEs precursors; however, the in vivo significance of this metabolic pathway during diabetes and obesity has not been fully assessed. Therefore we examined the role of AR in regulating ALEs and AGEs formation in murine models of diet-induced obesity and streptozotocin-induced diabetes. In comparison with wild-type (WT) and AR-null mice fed normal chow, mice fed a high-fat (HF) diet (42% kcal fat) showed increased accumulation of AGEs and protein-acrolein adducts in the plasma. AGEs and acrolein adducts were also increased in the epididymal fat of WT and AR-null mice fed a HF diet. Deletion of AR increased the accumulation of 4-hydroxy-trans-2-nonenal (HNE) protein adduct in the plasma and increased the expression of the AGE receptor (RAGE) in HF fed mice. No change in AGEs formation was observed in the kidneys of HF-fed mice. In comparison, renal tissue from AR-null mice treated with streptozotocin showed greater AGE accumulation than streptozotocin-treated WT mice. These data indicated that AR regulated the accumulation of lipid peroxidation derived aldehydes and AGEs under conditions of severe, but not mild, hyperglycemia and that deletion of AR increased RAGE-induction via mechanisms that were independent of AGEs accumulation.

  9. Role of thyrotropin-releasing hormone in prolactin-producing cell models.

    Science.gov (United States)

    Kanasaki, Haruhiko; Oride, Aki; Mijiddorj, Tselmeg; Kyo, Satoru

    2015-12-01

    Thyrotropin-releasing hormone (TRH) is a hypothalamic hypophysiotropic neuropeptide that was named for its ability to stimulate the release of thyroid-stimulating hormone in mammals. It later became apparent that it exerts a number of species-dependent hypophysiotropic activities that regulate other pituitary hormones. TRH also regulates the synthesis and release of prolactin, although whether it is a physiological regulator of prolactin that remains unclear. Occupation of the Gq protein-coupled TRH receptor in the prolactin-producing lactotroph increases the turnover of inositol, which in turn activates the protein kinase C pathway and the release of Ca(2+) from storage sites. TRH-induced signaling events also include the activation of extracellular signal-regulated kinase (ERK) and induction of MAP kinase phosphatase, an inactivator of activated ERK. TRH stimulates prolactin synthesis through the activation of ERK, whereas prolactin release occurs via elevation of intracellular Ca(2+). We have been investigating the role of TRH in a pituitary prolactin-producing cell model. Rat pituitary somatolactotroph GH3 cells, which produce and release both prolactin and growth hormone (GH), are widely used as a model for the study of prolactin- and GH-secreting cells. In this review, we describe the general action of TRH as a hypophysiotropic factor in vertebrates and focus on the role of TRH in prolactin synthesis using GH3 cells.

  10. Effects of the prototype serotonin 5-HT(1B/1D) receptor agonist sumatriptan and the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP(8-37) on myocardial reactive hyperemic response in conscious dogs.

    Science.gov (United States)

    Lynch, Joseph J; Shen, You-Tang; Pittman, Tamara J; Anderson, Kenneth D; Koblan, Kenneth S; Gould, Robert J; Regan, Christopher P; Kane, Stefanie A

    2009-11-25

    The triptans, serotonin 5-HT(1B/1D) receptor agonists exemplified by sumatriptan, are a mainstay migraine therapy but have class labeling contraindicating their use in patients with coronary artery disease. Triptans constrict human coronary artery in vitro, and there are case reports of myocardial infarction in patients using sumatriptan. However, preclinical studies with sumatriptan in normal dogs have failed to demonstrate effects on resting coronary flow. Calcitonin gene-related peptide (CGRP) receptor antagonism, exemplified by the prototype CGRP receptor antagonist peptide CGRP(8-37), is a new antimigraine mechanism which also has been reported to have no effect on coronary flow in normal, non-stressed animals. The goal of the present studies was to compare the effects of sumatriptan (10microg/kg/min i.v.) and CGRP(8-37) (30microg/kg/min i.v.) on systemic and coronary hemodynamics in conscious dogs under resting conditions and during myocardial reactive hyperemia following a brief 15s of coronary artery occlusion. Neither CGRP(8-37) nor sumatriptan affected resting coronary flow. However, whereas CGRP(8-37) had no effect on myocardial reactive hyperemic response, sumatriptan reduced peak reactive hyperemic coronary artery blood flow (baseline vs treatment: 75.4+/-12.7 vs 60.0+/-10.3ml/min, Ptriptan effects on coronary vascular function.

  11. Aryl hydrocarbon receptor regulates CYP1B1 but not ABCB1 and ABCG2 in hCMEC/D3 human cerebral microvascular endothelial cells after TCDD exposure.

    Science.gov (United States)

    Jacob, Aude; Potin, Sophie; Chapy, Hélène; Crete, Dominique; Glacial, Fabienne; Ganeshamoorthy, Kayathiri; Couraud, Pierre-Olivier; Scherrmann, Jean-Michel; Declèves, Xavier

    2015-07-10

    The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor activated by a variety of widespread persistent environmental pollutants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). It can transactivate the expression of several target genes. Recently AhR transcripts were detected in isolated human brain microvessels and in the hCMEC/D3 human cerebral microvascular endothelial cell line, an in vitro model of the human cerebral endothelium. To date AhR implication in the co-regulation of ABCB1, ABCG2 and CYP1B1 at human cerebral endothelium has not been addressed. Here we investigated whether AhR could co-regulate ABCB1, ABCG2 and CYP1B1 expressions in the hCMEC/D3 cell line. Exposure to TCDD induced a concentration-dependent increase in CYP1B1 expression. We demonstrated AhR involvement in the TCDD-mediated increase in CYP1B1 expression by using small interfering RNA against AhR. Western blotting analysis also revealed an increase in CYP1B1 protein expression following TCDD exposure in hCMEC/D3. Regarding ABCB1 and ABCG2, exposure to TCDD had no effect on their protein expressions and functional activities. In conclusion our data indicated a differential modulation of CYP1B1 and ABCB1/ABCG2 expressions in hCMEC/D3 cells following TCDD exposure.

  12. Possible crosstalk between leptin and prolactin during pregnancy.

    Science.gov (United States)

    Nagaishi, V S; Cardinali, L I; Zampieri, T T; Furigo, I C; Metzger, M; Donato, J

    2014-02-14

    Rodents exhibit leptin resistance and high levels of prolactin/placental lactogens during pregnancy. A crosstalk between prolactin and leptin signaling has been proposed as a possible mechanism to explain the changes in energy balance during gestation. However, it remains unclear if specific neuronal populations co-express leptin and prolactin receptors. Therefore, our present study was undertaken to identify in the mouse brain prolactin-responsive cells that possibly express the leptin receptor (LepR). In addition, we assessed the leptin response in different brain nuclei of pregnant and nulliparous mice. We used a LepR-reporter mouse to visualize LepR-expressing cells with the tdTomato fluorescent protein. Prolactin-responsive cells were visualized with the immunohistochemical detection of the phosphorylated form of the signal transducer and activator of transcription-5 (pSTAT5-ir). Notably, many neurons that co-expressed tdTomato and pSTAT5-ir were observed in the medial preoptic area (MPA, 27-48% of tdTomato cells), the retrochiasmatic area (34-51%) and the nucleus of the solitary tract (NTS, 16-24%) of prolactin-treated nulliparous mice, pregnant mice and prolactin-treated leptin-deficient (ob/ob) mice. The arcuate nucleus of the hypothalamus (8-22%), the medial tuberal nucleus (11-15%) and the ventral premammillary nucleus (4-10%) showed smaller percentages of double-labeled cells among the groups. Other brain nuclei did not show significant percentages of neurons that co-expressed tdTomato and pSTAT5-ir. Late pregnant mice exhibited a reduced leptin response in the MPA and NTS when compared with nulliparous mice; however, a normal leptin response was observed in other brain nuclei. In conclusion, our findings shed light on how the brain integrates the information conveyed by leptin and prolactin. Our results corroborate the hypothesis that high levels of prolactin or placental lactogens during pregnancy may directly interfere with LepR signaling, possibly

  13. Progress on Prolactin Receptor and Its Gene%催乳素受体及其基因的研究进展

    Institute of Scientific and Technical Information of China (English)

    张跟喜; 储明星; 王金玉

    2007-01-01

    催乳素(prolactin,PRL)是一种垂体前叶肽类激素,已报道的催乳素作用有300多种,可将它们分为六大类:繁殖和泌乳、生长和发育、内分泌和代谢、脑和行为、免疫调节和电解质平衡。这些作用均由催乳素受体(prolactin receptor,PRLR)调节。在脑、子宫、胚盘、卵巢等组织中已检测到了催乳素受体。催乳素受体属于细胞因子受体家族成员。国内外对催乳素受体的研究日益深入。文章主要对催乳素受体及其基因的研究进展作一简要介绍。

  14. Increased STAT5 signaling in the ring dove brain in response to prolactin administration and spontaneous elevations in prolactin during the breeding cycle.

    Science.gov (United States)

    Buntin, John D; Buntin, Linda

    2014-05-01

    Prolactin acts on target cells in the central nervous system (CNS) to stimulate behavioral changes associated with parental care in birds, but the signaling mechanisms that mediate these actions have not been characterized. In mammals, the Janus Kinase 2-Signal Transducer and Activator of Transcription 5 (JAK2-STAT5) signaling pathway mediates many of the actions of prolactin. To assess the importance of this pathway in prolactin-sensitive target cells in the avian brain, we measured changes in activated (phosphorylated) STAT5 (pSTAT5) in the forebrain of female ring doves sampled as plasma prolactin levels change during the breeding cycle and in prolactin-treated, non-breeding females. The anatomical distribution of cells exhibiting pSTAT5 immunoreactivity in dove brain closely paralleled the distribution of prolactin receptors in this species. The density of pSTAT5 immunoreactive (pSTAT5-ir) cells was highest in the preoptic area, the suprachiasmatic, paraventricular, and ventromedial hypothalamic nuclei, the lateral and tuberal hypothalamic regions, the lateral bed nucleus of the stria terminalis, and the lateral septum. Mean pSTAT5-ir cell densities in these eight brain areas were several fold higher in breeding females during late incubation/early post-hatching when plasma prolactin levels have been observed to peak than in non-breeding females or breeding females sampled at earlier stages when prolactin titers have been reported to be lower. Similar differences were observed between prolactin-treated and vehicle-treated females in all three of the forebrain regions that were compared. We conclude that JAK2-STAT5 signaling is strongly activated in response to prolactin stimulation in the ring dove brain and could potentially mediate some of the centrally-mediated behavioral effects of this hormone.

  15. Molecular characterization of two suppressor of cytokine signaling 1 genes (SOCS1a and SOCS1b in chickens

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    Xue XU,Jiannan ZHANG,Juan LI,Yajun WANG

    2015-03-01

    Full Text Available Suppressor of cytokine signaling 1 (SOCS1 protein can inhibit the signal transduction triggered by some cytokines or hormones and thus are important in many physiological/pathological processes, including innate and adaptive immunity, inflammation, and development in mammals. However, there is sparse information about their structure, tissue expression, in birds, where their biological functions remain unknown. In this study, we cloned and characterized two SOCS1 genes (named cSOCS1a and cSOCS1b from chickens. SOCS1a is predicted to encode a 207-amino acid protein, which shares high amino acid sequence identity (64%–67% with human and mouse SOCS1. Besides SOCS1a, a novel SOCS1b gene was also identified in chickens and other non-mammalian vertebrates including Xenopus tropicalis. Chicken SOCS1b is predicted to encode a 212-amino acid protein, which shares only 30%–32% amino acid sequence identity with human SOCS1 and cSOCS1a. RT-PCR assay revealed that both cSOCS1a and cSOCS1b are widely expressed in all chicken tissues. Using a luciferase reporter assay system, we further demonstrated that transient expression of cSOCS1a and cSOCS1b can significantly inhibit chicken growth hormone (GH- or prolactin (PRL-induced luciferase activities of Hep G2 cells expressing cGH receptor (or cPRL receptor, indicating that SOCS1a and SOCS1b proteins can negatively regulate GH/PRL signaling. Taken together, these data suggest that both cSOCS1a and cSOCS1b may function as negative regulators of cytokine/hormone actions, such as modulation of GH/PRL actions in chickens.

  16. Prior reproductive experience alters prolactin-induced macrophage responses in pregnant rats.

    Science.gov (United States)

    Carvalho-Freitas, Maria Isabel Roth; Anselmo-Franci, Janete A; Palermo-Neto, João; Felicio, Luciano F

    2013-09-01

    Reproductive experience (i.e., pregnancy and lactation) induces physiological changes in mammals. A previous reproductive experience was recently shown to modulate the activity of dopaminergic hypothalamic systems while decreasing serum prolactin levels and oxidative burst activity in peritoneal macrophages. Dopamine receptor antagonists increase serum prolactin levels, and both prolactin and dopamine receptors may be involved in the modulation of macrophage activity, providing a means of communication between the nervous and immune systems. The present study evaluated the in vitro effects of prolactin and a dopamine D2 receptor antagonist on the peritoneal activity of macrophages from primigravid and multigravid female rats during the third trimester of pregnancy. Oxidative bursts and phagocytosis in peritoneal macrophages were evaluated by flow cytometry. Primigravid and multigravid Wistar rats, during the third trimester of pregnancy (i.e., days 17-21), were used. Peritoneal fluid samples from these rats were first incubated with prolactin (10 and 100 nM) for different periods of time. The same procedure was repeated to evaluate the effects of domperidone (10 and 100 nM) on macrophage activity. Our results showed that macrophages from multigravid rats responded more effectively to in vitro incubation with prolactin, especially with regard to the intensity and percentage of phagocytosis. Additionally, these effects were more pronounced after incubation periods of 30 min or 4 h. These data suggest that macrophages during a second pregnancy become more sensitive to the phagocytotic effects of prolactin.

  17. The Combination of Marketed Antagonists of α1b-Adrenergic and 5-HT2A Receptors Inhibits Behavioral Sensitization and Preference to Alcohol in Mice: A Promising Approach for the Treatment of Alcohol Dependence.

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    Fabrice Trovero

    Full Text Available Alcohol-dependence is a chronic disease with a dramatic and expensive social impact. Previous studies have indicated that the blockade of two monoaminergic receptors, α1b-adrenergic and 5-HT2A, could inhibit the development of behavioral sensitization to drugs of abuse, a hallmark of drug-seeking and drug-taking behaviors in rodents. Here, in order to develop a potential therapeutic treatment of alcohol dependence in humans, we have blocked these two monoaminergic receptors by a combination of antagonists already approved by Health Agencies. We show that the association of ifenprodil (1 mg/kg and cyproheptadine (1 mg/kg (α1-adrenergic and 5-HT2 receptor antagonists marketed as Vadilex ® and Periactine ® in France, respectively blocks behavioral sensitization to amphetamine in C57Bl6 mice and to alcohol in DBA2 mice. Moreover, this combination of antagonists inhibits alcohol intake in mice habituated to alcohol (10% v/v and reverses their alcohol preference. Finally, in order to verify that the effect of ifenprodil was not due to its anti-NMDA receptors property, we have shown that a combination of prazosin (0.5 mg/kg, an α1b-adrenergic antagonist, Mini-Press ® in France and cyproheptadine (1 mg/kg could also reverse alcohol preference. Altogether these findings strongly suggest that combined prazosin and cyproheptadine could be efficient as a therapy to treat alcoholism in humans. Finally, because α1b-adrenergic and 5-HT2A receptors blockade also inhibits behavioral sensitization to psychostimulants, opioids and tobacco, it cannot be excluded that this combination will exhibit some efficacy in the treatment of addiction to other abused drugs.

  18. Receptor-mediated stimulation of lipid signalling pathways in CHO cells elicits the rapid transient induction of the PDE1B isoform of Ca2+/calmodulin-stimulated cAMP phosphodiesterase.

    Science.gov (United States)

    Spence, S; Rena, G; Sullivan, M; Erdogan, S; Houslay, M D

    1997-01-01

    Chinese hamster ovary cells (CHO cells) do not exhibit any Ca2+/calmodulin-stimulated cAMP phosphodiesterase (PDE1) activity. Challenge of CHO cells with agonists for endogenous P2-purinoceptors, lysophosphatidic acid receptors and thrombin receptors caused a similar rapid transient induction of PDE1 activity in each instance. This was also evident on noradrenaline challenge of a cloned CHO cell line transfected so as to overexpress alpha 1B-adrenoceptors. This novel PDE1 activity appeared within about 15 min of exposure to ligands, rose to a maximum value within 30 min to 1 h and then rapidly decreased. In each case, the expression of novel PDE1 activity was blocked by the transcriptional inhibitor actinomycin D. Challenge with insulin of either native CHO cells or a CHO cell line transfected so as to overexpress the human insulin receptor failed to induce PDE1 activity. Reverse transcriptase-PCR analyses, using degenerate primers able to detect the PDE1C isoform, did not amplify any fragment from RNA preparations of CHO cells expressing PDE1 activity, although they did so from the human thyroid carcinoma FTC133 cell line. Reverse transcriptase-PCR analyses, using degenerate primers able to detect the PDE1A and PDE1B isoforms, successfully amplified a fragment of the predicted size from RNA preparations of both CHO cells expressing PDE1 activity and human Jurkat T-cells. Sequencing of the PCR products, generated using the PDE1A/B primers, yielded a novel sequence which, by analogy with sequences reported for bovine and murine PDE1B forms, suggests that the PDE1 species induced in CHO cells through protein kinase C activation and that expressed in Jurkat T-cells are PDE1B forms.

  19. Functionally reciprocal mutations of the prolactin signalling pathway define hairy and slick cattle.

    Science.gov (United States)

    Littlejohn, Mathew D; Henty, Kristen M; Tiplady, Kathryn; Johnson, Thomas; Harland, Chad; Lopdell, Thomas; Sherlock, Richard G; Li, Wanbo; Lukefahr, Steven D; Shanks, Bruce C; Garrick, Dorian J; Snell, Russell G; Spelman, Richard J; Davis, Stephen R

    2014-12-18

    Lactation, hair development and homeothermy are characteristic evolutionary features that define mammals from other vertebrate species. Here we describe the discovery of two autosomal dominant mutations with antagonistic, pleiotropic effects on all three of these biological processes, mediated through the prolactin signalling pathway. Most conspicuously, mutations in prolactin (PRL) and its receptor (PRLR) have an impact on thermoregulation and hair morphology phenotypes, giving prominence to this pathway outside of its classical roles in lactation.

  20. Triclosan activates aryl hydrocarbon receptor (AhR)-dependent apoptosis and affects Cyp1a1 and Cyp1b1 expression in mouse neocortical neurons.

    Science.gov (United States)

    Szychowski, Konrad A; Wnuk, Agnieszka; Kajta, Małgorzata; Wójtowicz, Anna K

    2016-11-01

    Triclosan (TCS) is an antimicrobial agent that is used extensively in personal care and in sanitizing products, such as soaps, toothpastes, and hair products. A number of studies have revealed the presence of TCS in human tissues, such as fat, liver and brain, in addition to blood and breast milk. The aim of the present study was to investigate the impact of TCS on AhR and Cyp1a1/Cyp1b1 signaling in mouse neocortical neurons in primary cultures. In addition to the use of selective ligands and siRNAs, expression levels of mRNA and proteins as well as caspase-3 activity, reactive oxygen species (ROS) formation, and lactate dehydrogenase (LDH) release have been measured. We also studied the involvement of the AhR in TCS-induced LDH release and caspase-3 activation as well as the effect of TCS on ROS generation. Cultures of neocortical neurons were prepared from Swiss mouse embryos on day 15/16 of gestation. The cells were cultured in phenol red-free Neurobasal medium with B27 and glutamine, and the neurons were exposed to 1 and 10µM TCS. Our experiments showed that the expression of AhR and Cyp1a1 mRNA decreased in cells exposed to 10µM TCS for 3 or 6h. In the case of Cyp1b1, mRNA expression remained unchanged compared with the control group following 3h of exposure to TCS, but after 6h, the mRNA expression of Cyp1b1 was decreased. Our results confirmed that the AhR is involved in the TCS mechanism of action, and our data demonstrated that after the cells were transfected with AhR siRNA, the cytotoxic and pro-apoptotic properties of TCS were decreased. The decrease in Cyp1a1 mRNA and protein expression levels accompanied by a decrease in its activity. The stimulation of Cyp1a1 activity produced by the application of an AhR agonist (βNF) was attenuated by TCS, whereas the addition of AhR antagonist (αNF) reversed the inhibitory effects of TCS. In our experiments, TCS diminished Cyp1b1 mRNA and enhanced its protein expression. In case of Cyp1a1 we observed

  1. 17-beta-estradiol-dependent regulation of somatostatin receptor subtype expression in the 7315b prolactin secreting rat pituitary tumor in vitro and in vivo

    NARCIS (Netherlands)

    H.A. Visser-Wisselaar (Heleen); C.J. van Uffelen; P.M. van Koetsveld (Peter); E.G. Lichtenauer-Kaligis; A.M. Waaijers (Annet); P. Uitterlinden (Piet); D.M. Mooy; S.W.J. Lamberts (Steven); L.J. Hofland (Leo)

    1997-01-01

    textabstractIn the present study, we have investigated the role of estrogens in the regulation of somatostatin receptor subtype (sst) expression in 7315b PRL-secreting rat pituitary tumor cells in vitro and in vivo. sst were undetectable in freshly dispersed cells of the transplant

  2. Zolmitriptan (a 5-HT1B/1D receptor agonist with central action) does not increase symptoms in obsessive compulsive disorder

    NARCIS (Netherlands)

    Boshuisen, ML; den Boer, JA

    2000-01-01

    Rationale: Non-selective serotonin (5-HT) receptor agonists like meta-chlorophenylpiperazine and MK-212 have been used to explore the role of 5-HT in obsessive compulsive disorder (OCD). The results of these studies and the findings of autoradiography and neuroimaging studies, pointed to a possible

  3. [THE THYROID STATUS OF RATS IMMUNIZED WITH PEPTIDES DERIVED FROM THE EXTRACELLULAR REGIONS OF THE TYPES 3 AND 4 MELANOCORTIN RECEPTORS AND THE 1B-SUBTYPE 5-HYDROXYTRYPTAMINE RECEPTOR].

    Science.gov (United States)

    Derkach, K V; Moyseuk, I V; Shpakova, E A; Sphakov, A O

    2015-01-01

    The activity of the hypothalamic-pituitary-thyroid (HPT) axis is controlled by the brain neurotransmitter systems, including the melanocortin signaling system. Pharmacological inhibition of type 4 melanocortin receptor (M4R) leads to disruption of the functioning of HPT axis and to reduction of the level of thyroid hormones. At the same time, the data on how prolonged inhibition of M4R affects this axis and on its role in regulation of M3R are absent. The relationship between the thyroid status and the activity of 1B-subtype 5-hydroxytryptamine receptor (5-HT1BR) is scarcely explored. The aim of this work to study the effects of chronic inhibition of M3R, M4R and 5-HT1BR induced by immunization of rats with BSA-conjugated peptide derived from the extracellular regions of these receptors on the thyroid status and the activity of thyroid stimulating hormone (TSH)-sensitive adenylyl cyclase signaling system (ACSS) in the thyroid glarid (TG) of the immunized animals. In rats immunized with the peptides K-[TSLHL WNRSSHGLHG11-25]-A of M4R, A[PTNPYCICTTAH269-280]-A of M3R and. [QAKAEE-EVSEC(Acm)-VVNTDH189-205]-A of 5-HT1BR levels of thyroid hormones such as fT4, tT4 and tT3 were significantly reduced. In rats immunized with M4R and M3R peptides, an increase of TSH was detected whereas in the animals immunized with 5-HT1BR peptide the level of TSH, on the contrary, was reduced. In the TG of rats immunized with M4R and M3R peptides, the stimulatory effects of hormones (TSH, PA-CAP-3 8) and GppNHp on adenylyl cyclase activity were attenuated, and the changes were most pronounced in the case M4R peptide immunization. After immunization with 5-HT1BR peptide the stimulatory effects of TSH, PACAP-38 and GppNHp were retained. Thus, the main cause of thyroid hormones deficit in rats immunized with M4R and M3R peptides was the decreased sensitivity of ACSS thyrocytes to TSH, whereas in rats iimunized with 5-HT1BR peptide the deficit of thyroid hormones was associated with decreased

  4. Pindolol pretreatment blocks stimulation by meta-chlorophenylpiperazine of prolactin but not cortisol secretion in normal men.

    Science.gov (United States)

    Meltzer, H Y; Maes, M

    1995-09-29

    Previous reports from this laboratory have shown that pindolol, a partial serotonin1A receptor agonist, inhibited prolactin, but not cortisol secretion induced by administration of the serotonin (5-HT) precursor L-5-hydroxytryptophan or the direct-acting 5-HT2A/5HT2C receptor agonist MK-212. The findings suggest additive or interactive effects of 5-HT1A and 5-HT2A/5-HT2C receptors in modulating 5-HT-related prolactin, but not cortisol, responsivity. To examine further the role of 5-HT1A and 5-HT2A/5-HT2C receptors in prolactin and cortisol secretion in healthy men, the effects of meta-chlorophenylpiperazine (mCPP), a potent 5-HT receptor agonist, on the above hormones were studied in eight healthy men with and without pindolol pretreatment. It has previously been demonstrated that ketanserin, a 5-HT2A antagonist, and ritanserin, a 5-HT2A/5-HT2C antagonist, block the prolactin and attenuate the hypothalamic-pituitary-adrenal axis responses to mCPP in man or rodents. Administration of mCPP induced a significant increase in plasma concentrations of prolactin and cortisol. The mCPP-induced prolactin concentrations were significantly blocked by pretreatment with pindolol, whereas mCPP-stimulated cortisol levels were not diminished by pindolol pretreatment. Thus, mCPP-induced prolactin secretion appears to require the availability of both 5-HT2C and 5-HT1A receptor activation, since blockade of either of these receptors may diminish the mCPP-induced prolactin response. Cortisol secretion stimulated by mCPP may occur following 5-HT2C receptor stimulation in the presence of 5-HT1A receptor blockade.

  5. Prolactin inhibits a major tumor-suppressive function of wild type BRCA1.

    Science.gov (United States)

    Chen, Kuan-Hui Ethan; Walker, Ameae M

    2016-06-01

    Even though mutations in the tumor suppressor, BRCA1, markedly increase the risk of breast and ovarian cancer, most breast and ovarian cancers express wild type BRCA1. An important question is therefore how the tumor-suppressive function of normal BRCA1 is overcome during development of most cancers. Because prolactin promotes these and other cancers, we investigated the hypothesis that prolactin interferes with the ability of BRCA1 to inhibit the cell cycle. Examining six different cancer cell lines with wild type BRCA1, and making use of both prolactin and the growth-inhibiting selective prolactin receptor modulator, S179D PRL, we demonstrate that prolactin activation of Stat5 results in the formation of a complex between phospho-Stat5 and BRCA1. Formation of this complex does not interfere with nuclear translocation or binding of BRCA1 to the p21 promoter, but does interfere with the ability of BRCA1 to transactivate the p21 promoter. Overexpression of a dominant-negative Stat5 in prolactin-stimulated cells resulted in increased p21 expression. We conclude that prolactin inhibits a major tumor-suppressive function of BRCA1 by interfering with BRCA1's upregulation of expression of the cell cycle inhibitor, p21.

  6. Social approach behaviors are similar on conventional versus reverse lighting cycles, and in replications across cohorts, in BTBR T+ tf/J, C57BL/6J, and vasopressin receptor 1B mutant mice

    Directory of Open Access Journals (Sweden)

    Mu Yang

    2007-11-01

    Full Text Available Mice are a nocturnal species, whose social behaviors occur primarily during the dark phase of the circadian cycle. However, laboratory rodents are frequently tested during their light phase, for practical reasons. We investigated the question of whether light phase testing presents a methodological pitfall for investigating mouse social approach behaviors. Three lines of mice were systematically compared. One cohort of each line was raised in a conventional lighting schedule and tested during the light phase, under white light illumination; another cohort was raised in a reverse lighting schedule and tested during their dark phase, under dim red light. Male C57BL/6J (B6 displayed high levels of sociability in our three-chambered automated social approach task when tested in either phase. BTBR T+ tf/J (BTBR displayed low levels of sociability in either phase. Five cohorts of vasopressin receptor subtype 1b (Avpr1b null mutants, heterozygotes, and wildtype littermate controls were tested in the same social approach paradigm: three in the dark phase and two in the light phase. All three genotypes displayed normal sociability in four out of the five replications. In the juvenile play test, testing phase had no effect on play soliciting behaviors in Avpr1b mice, but had modest effects on nose sniff and huddling. Taken together, these findings indicate that testing phase is not a crucial factor for studying some forms of social approach in juvenile and adult mice.

  7. The brain vasopressin system mediates maternal behaviour in lactating rats - impact of V1b receptors in hypothalamic and limbic brain regions

    OpenAIRE

    Bayerl, Doris

    2017-01-01

    Adequate maternal behaviour offers the best chance for the offspring to survive to maturity. This pro-social behaviour is known to be regulated by the nonapeptide arginine-vasopressin (AVP) amongst other peptidergic and non-peptidergic systems in rodents as well as in humans. Most research regarding the AVP system in maternal behaviour has focussed on the peptide itself and its V1a receptor (V1aR), and revealed a pivotal involvement in the regulation of different aspects of maternal behaviour...

  8. Interplay between progesterone and prolactin in mammary development and implications for breast cancer.

    Science.gov (United States)

    Lee, Heather J; Ormandy, Christopher J

    2012-06-24

    Progesterone and prolactin remodel mammary morphology during pregnancy by acting on the mammary epithelial cell hierarchy. The roles of each hormone in mammary development have been well studied, but evidence of signalling cross-talk between progesterone and prolactin is still emerging. Factors such as receptor activator of NFkB ligand (RANKL) may integrate signals from both hormones to orchestrate their joint actions on the epithelial cell hierarchy. Common targets of progesterone and prolactin signalling are also likely to integrate their pro-proliferative actions in breast cancer. Therefore, a thorough understanding of the interplay between progesterone and prolactin in mammary development may reveal therapeutic targets for breast cancer. This review summarises our understanding of Pg and PRL action in mammary gland development before focusing on molecular mechanisms of signalling cross-talk and the implications for breast cancer.

  9. An Unexpected Mode Of Binding Defines BMS948 as A Full Retinoic Acid Receptor β (RARβ, NR1B2 Selective Agonist.

    Directory of Open Access Journals (Sweden)

    Eswarkumar Nadendla

    Full Text Available Retinoic acid is an important regulator of cell differentiation which plays major roles in embryonic development and tissue remodeling. The biological action of retinoic acid is mediated by three nuclear receptors denoted RARα, β and γ. Multiple studies support that RARβ possesses functional characteristics of a tumor suppressor and indeed, its expression is frequently lost in neoplastic tissues. However, it has been recently reported that RARβ could also play a role in mammary gland tumorigenesis, thus demonstrating the important but yet incompletely understood function of this receptor in cancer development. As a consequence, there is a great need for RARβ-selective agonists and antagonists as tools to facilitate the pharmacological analysis of this protein in vitro and in vivo as well as for potential therapeutic interventions. Here we provide experimental evidences that the novel synthetic retinoid BMS948 is an RARβ-selective ligand exhibiting a full transcriptional agonistic activity and activating RARβ as efficiently as the reference agonist TTNPB. In addition, we solved the crystal structures of the RARβ ligand-binding domain in complex with BMS948 and two related compounds, BMS641 and BMS411. These structures provided a rationale to explain how a single retinoid can be at the same time an RARα antagonist and an RARβ full agonist, and revealed the structural basis of partial agonism. Finally, in addition to revealing that a flip by 180° of the amide linker, that usually confers RARα selectivity, accounts for the RARβ selectivity of BMS948, the structural analysis uncovers guidelines for the rational design of RARβ-selective antagonists.

  10. Glucocorticoid receptor 1B and 1C mRNA transcript alterations in schizophrenia and bipolar disorder, and their possible regulation by GR gene variants.

    Science.gov (United States)

    Sinclair, Duncan; Fullerton, Janice M; Webster, Maree J; Shannon Weickert, Cynthia

    2012-01-01

    Abnormal patterns of HPA axis activation, under basal conditions and in response to stress, are found in individuals with schizophrenia and bipolar disorder. Altered glucocorticoid receptor (GR) mRNA and protein expression in the dorsolateral prefrontal cortex (DLPFC) in psychiatric illness have also been reported, but the cause of these abnormalities is not known. We quantified expression of GR mRNA transcript variants which employ different 5' promoters, in 35 schizophrenia cases, 31 bipolar disorder cases and 34 controls. We also explored whether sequence variation within the NR3C1 (GR) gene is related to GR mRNA variant expression. Total GR mRNA was decreased in the DLPFC in schizophrenia cases relative to controls (15.1%, pbipolar disorder cases (8.9%, pschizophrenia cases relative to controls (20.2%, pschizophrenia and bipolar disorder cases relative to controls (16.1% and 17.2% respectively, both pgene expression changes in psychotic illness, and highlight the potential importance of sequence variation within the NR3C1 gene in modulating GR mRNA expression in the DLPFC.

  11. Prolactin has a pathogenic role in systemic lupus erythematosus.

    Science.gov (United States)

    Jara, Luis J; Medina, Gabriela; Saavedra, Miguel A; Vera-Lastra, Olga; Torres-Aguilar, Honorio; Navarro, Carmen; Vazquez Del Mercado, Monica; Espinoza, Luis R

    2017-01-28

    Prolactin, a 23-kDa peptide hormone, is produced by the anterior pituitary gland and extrapituitary sites including the immune cells. Prolactin (PRL) participates in innate and adaptive immune response. PRL stimulates the immune cells by binding to receptor (PRL-R). Binding of PRL to its receptor activates the Janus kinase-signal transducer (JAK-STAT). Activation of these cascades results in endpoints such as immunoestimulator and immunosupressor action. Prolactin belongs to the network of immune-neuroendocrine interaction. Hyperprolactinemia has been found in patients with systemic lupus erythematosus (SLE), and new evidence has confirmed a significant correlation between serum PRL levels and disease activity. PRL participates in activation of SLE during pregnancy and in pathogenesis of lupus nephritis, neuropsychiatric, serosal, hematologic, articular, and cutaneous involvement. Hyperprolactinemia was associated with increase IgG concentrations, anti-DNA antibodies, immune complex, glomerulonephritis, and accelerated mortality in murine lupus. Bromocriptine, a dopamine analog that suppresses PRL secretion, was associated with decreased lupus activity, prolonged lifespan, and restoration of immune competence in experimental model. In clinical trials, bromocriptine and derivative drugs showed beneficial therapeutic effect in treating human lupus, including pregnancy. Taken together, clinical and experimental results leave little doubt that PRL indeed contributes to the pathogenesis and clinical expression of SLE.

  12. 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

    2008-01-01

    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

  13. MGC9753 gene, located within PPP1R1B-STARD3-ERBB2-GRB7 amplicon on human chromosome 17q12, encodes the seven-transmembrane receptor with extracellular six-cystein domain.

    Science.gov (United States)

    Katoh, Masuko; Katoh, Masaru

    2003-06-01

    MYC, ERBB2, MET, FGFR2, CCNE1, MYCN, WNT2, CD44, MDM2, NCOA3, IQGAP1 and STK6 loci are amplified in human gastric cancer. It has been reported that the gene corresponding to EST H16094 is co-amplified with ERBB2 gene in human gastric cancer. Here, we identified and characterized the gene corresponding to EST H16094 by using bioinformatics. BLAST programs revealed that EST H16094 was derived from the uncharacterized MGC9753 gene. Two ORFs were predicted within human MGC9753 mRNA, and ORF1 (nucleotide position 18-980 of NM_033419.1) was predicted as the coding region of human MGC9753 mRNA based on comparative genomics. Nucleotide sequence of mouse Mgc9753 mRNA was next determined in silico by modification of AK052486 cDNA (deleting C at the nucleotide position 37). Human MGC9753 and mouse Mgc9753 proteins were 320-amino-acid seven-transmembrane receptors with the N-terminal six-cysteine domain and an N-glycosylation site (85.0% total-amino-acid identity). Human MGC9753 protein showed 90.6% total-amino-acid identity with human CAB2 aberrant protein, which lacked the third-transmembrane domain of MGC9753 due to frame shifts within ORF. Human MGC9753 gene, consisting of eight exons, were clustered with PPP1R1B, STARD3, TCAP, PNMT, ERBB2, MGC14832 and GRB7 genes within the 120-kb region. PPP1R1B, STARD3, MGC9753, ERBB2 and GRB7 genes are co-amplified in several cases of gastric cancer. This is the first report on comprehensive characterization of the amplicon around the PPP1R1B-STARD3-TCAP-PNMT-MGC9753-ERBB2-MGC14832-GRB7 locus on human chromosome 17q12.

  14. Effects of the 5-HT1B receptor antagonist NAS-181 on extracellular levels of acetylcholine, glutamate and GABA in the frontal cortex and ventral hippocampus of awake rats: a microdialysis study.

    Science.gov (United States)

    Hu, Xiao Jing; Wang, Fu-Hua; Stenfors, Carina; Ogren, Sven Ove; Kehr, Jan

    2007-09-01

    The purpose of this study was to investigate the effects of the 5-HT(1B) receptor antagonist NAS-181 ((R)-(+)-2-(3-morpholinomethyl-2H-chromen-8-yl) oxymethyl-morpholine methanesulfonate) on cholinergic, glutamatergic and GABA-ergic neurotransmission in the rat brain in vivo. Extracellular levels of acetylcholine, glutamate and GABA were monitored by microdialysis in the frontal cortex (FC) and ventral hippocampus (VHipp) in separate groups of freely moving rats. NAS-181 (1, 5 or 10 mg/kg, s.c.) caused a dose-dependent increase in ACh levels, reaching the maximal values of 500% (FC) and 230% (VHipp) of controls at 80 min post-injection. On the contrary, NAS-181 injected at doses of 10 or 20 mg/kg s.c. had no effect on basal extracellular levels of Glu and GABA in these areas. The present data suggest that ACh neurotransmission in the FC and VHipp, the brain structures strongly implicated in cognitive function, is under tonic inhibitory control of 5-HT(1B) heteroreceptors localized at the cholinergic terminals in these areas.

  15. Interferon Gamma-1b Injection

    Science.gov (United States)

    Interferon gamma-1b injection is used to reduce the frequency and severity of serious infections in people with ... with severe, malignant osteopetrosis (an inherited bone disease). Interferon gamma-1b is in a class of medications called ...

  16. Stimulation of 5-HT1A, 5-HT1B, 5-HT2A/2C, 5-HT3 and 5-HT4 receptors or 5-HT uptake inhibition: short- and long-term memory.

    Science.gov (United States)

    Meneses, Alfredo

    2007-11-22

    In order to determine whether short- (STM) and long-term memory (LTM) function in serial or parallel manner, serotonin (5-hydroxtryptamine, 5-HT) receptor agonists were tested in autoshaping task. Results show that control-vehicle animals were modestly but significantly mastering the autoshaping task as illustrated by memory scores between STM and LTM. Thus, post-training administration of 8-OHDPAT (agonist for 5-HT(1A/7) receptors) only at 0.250 and 0.500 mg/kg impaired both STM and LTM. CGS12066 (agonist for 5-HT(1B)) produced biphasic affects, at 5.0 mg/kg impaired STM but at 1.0 and 10.0 mg/kg, respectively, improved or impaired LTM. DOI (agonist for 5-HT(2A/2C) receptors) dose-dependently impaired STM and, at 10.0 mg/kg only impaired LTM. Both, STM and LTM were impaired by either mCPP (mainly agonist for 5-HT(2C) receptors) or mesulergine (mainly antagonist for 5-HT(2C) receptors) lower dose. The 5-HT(3) agonist mCPBG at 1.0 impaired STM and its higher dose impaired both STM and LTM. RS67333 (partial agonist for 5-HT(4) receptors), at 5.0 and 10.0 mg/kg facilitated both STM and LTM. The higher dose of fluoxetine (a 5-HT uptake inhibitor) improved both STM and LTM. Using as head-pokes during CS as an indirect measure of food-intake showed that of 30 memory changes, 21 of these were unrelated to the former. While some STM or LTM impairments can be attributed to decrements in food-intake, but not memory changes (either increase or decreases) produced by 8-OHDPAT, CGS12066, RS67333 or fluoxetine. Except for animals treated with DOI, mCPBG or fluoxetine, other groups treated with 5-HT agonists 6 h following autoshaping training showed similar LTM and unmodified CS-head-pokes scores.

  17. Increased serum prolactin in borderline personality disorder.

    Science.gov (United States)

    Atmaca, Murad; Korkmaz, Sevda; Ustundag, Bilal; Ozkan, Yusuf

    2015-01-01

    Although there is an important interaction between serotonergic system, prolactin and suicidal behavior, and impulsivity, no investigation examined the prolactin values in borderline personality disorder in which suicidal behavior and impulsivity are core symptom dimensions. In this context, in the present investigation, we planned to measure serum prolactin levels in the patients with borderline personality disorder. The study comprised 15 patients with borderline personality disorder and 15 healthy controls. Prolactin values were measured in both patients and control subjects. The patients had abnormally higher mean value of prolactin compared to those of healthy controls (48.66 ± 36.48 mg/dl for patients vs. 15.20 ± 7.81 mg/dl for healthy controls). There was no correlation between prolactin values and any demographic variables for both the patients and control subjects. In conclusion, our present results suggest that prolactin values increased in the patients with borderline personality disorder and are required to be replicated by more comprehensive and detailed further studies to decipher the exact roles of prolactin increase.

  18. Acute elevation of endogenous prolactin does not influence glucose homeostasis in healthy men.

    Science.gov (United States)

    Vigas, M; Klimes, I; Jurcovicová, J; Jezová, D

    1993-01-01

    The diabetogenic effect of prolactin observed in patients with pathological hyperprolactinaemia was verified in healthy subjects. Plasma prolactin elevation was induced by administration of a dopamine antagonist drug domperidone (Motilium 10 mg orally, 9 subjects) and 2 h later the oral glucose tolerance test was performed. The influence of dopamine receptor stimulation on glucose homeostasis was tested by dopamine infusion (0.3 mg in saline or 20% glucose, 1 g/min for 60 min, 11 subjects). After the blockade of dopamine receptors, a significant and prolonged increase of prolactin concentration was found. However, the levels of glucose, insulin, and C-peptide either before or after the glucose load were not different from control ones. The decreased number of insulin receptors (1.97 +/- 0.41 vs 0.51 +/- 0.14 pmol per 2.10(9) red blood cells) was compensated by increased affinity (0.51 +/- 0.17 vs 1.00 +/- 0.22 Ke 10(8) mol.-1 per l]) of insulin receptors. The stimulation of dopamine receptors showed a negligible effect on glucose regulation. It may be suggested that an endogenous increase of prolactin concentration in the physiological range does not participate in the regulation of glucose homeostasis in healthy subjects.

  19. Increased Insulin following an Oral Glucose Load, Genetic Variation near the Melatonin Receptor MTNR1B, but No Biochemical Evidence of Endothelial Dysfunction in Young Asian Men and Women.

    Directory of Open Access Journals (Sweden)

    Maria A Matuszek

    Full Text Available To identify biochemical and genetic variation relating to increased risk of developing type 2 diabetes mellitus and cardiovascular disease in young, lean male and female adults of different ethnicities.Fasting blood and urine and non-fasting blood following oral glucose intake were analysed in 90 Caucasians, South Asians and South East/East Asians.There were no differences in age, birthweight, blood pressure, body mass index, percent body fat, total energy, percentage of macronutrient intake, microalbumin, leptin, cortisol, adrenocorticotropic hormone, nitric oxide metabolites, C-reactive protein, homocysteine, tumor necrosis factor-α, interleukin-6, von Willebrand factor, vascular cell adhesion molecule-1, plasminogen activator inhibitor-1, and tissue plasminogen activator. Fasting total cholesterol (P = .000, triglycerides (P = .050, low density lipoprotein (P = .009 and non-fasting blood glucose (15 min (P = .024 were elevated in South Asians compared with Caucasians, but there was no significant difference in glucose area under curve (AUC. Non-fasting insulin in South Asians (15-120 min, in South East/East Asians (60-120 min, and insulin AUC in South Asians and South East/East Asians, were elevated compared with Caucasians (P≤0.006. The molar ratio of C-peptide AUC/Insulin AUC (P = .045 and adiponectin (P = .037 were lower in South Asians compared with Caucasians. A significant difference in allele frequency distributions in Caucasians and South Asians was found for rs2166706 (P = 0.022 and rs10830963 (P = 0.009, which are both near the melatonin receptor MTNR1B.Elevated non-fasting insulin exists in young South Asians of normal fasting glucose and insulin. Hepatic clearance of insulin may be reduced in South Asians. No current biochemical evidence exists of endothelial dysfunction at this stage of development. MTNR1B signalling may be a useful therapeutic target in Asian populations in the prevention of type 2 diabetes mellitus.

  20. 21 CFR 862.1625 - Prolactin (lactogen) test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Prolactin (lactogen) test system. 862.1625 Section... Systems § 862.1625 Prolactin (lactogen) test system. (a) Identification. A prolactin (lactogen) test system is a device intended to measure the anterior pituitary polypeptide hormone prolactin in serum...

  1. Function of Treg Cells Decreased in Patients With Systemic Lupus Erythematosus Due To the Effect of Prolactin.

    Science.gov (United States)

    Legorreta-Haquet, María Victoria; Chávez-Rueda, Karina; Chávez-Sánchez, Luis; Cervera-Castillo, Hernando; Zenteno-Galindo, Edgar; Barile-Fabris, Leonor; Burgos-Vargas, Rubén; Álvarez-Hernández, Everardo; Blanco-Favela, Francisco

    2016-02-01

    Prolactin has different functions, including cytokine secretion and inhibition of the suppressor effect of regulatory T (Treg) cells in healthy individuals. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by defects in the functions of B, T, and Treg cells. Prolactin plays an important role in the physiopathology of SLE. Our objective was to establish the participation of prolactin in the regulation of the immune response mediated by Treg cells from patients with SLE. CD4CD25CD127 cells were purified using magnetic beads and the relative expression of prolactin receptor was measured. The functional activity was evaluated by proliferation assay and cytokine secretion in activated cells, in the presence and absence of prolactin. We found that both percentage and function of Treg cells decrease in SLE patients compared to healthy individuals with statistical significance. The prolactin receptor is constitutively expressed on Treg and effector T (Teff) cells in SLE patients, and this expression is higher than in healthy individuals. The expression of this receptor differs in inactive and active patients: in the former, the expression is higher in Treg cells than in Teff cells, similar to healthy individuals, whereas there is no difference in the expression between Treg and Teff cells from active patients. In Treg:Teff cell cocultures, addition of prolactin decreases the suppressor effect exerted by Treg cells and increases IFNγ secretion. Our results suggest that prolactin plays an important role in the activation of the disease in inactive patients by decreasing the suppressor function exerted by Treg cells over Teff cells, thereby favoring an inflammatory microenvironment.

  2. Prolactin and growth hormone in fish osmoregulation

    Science.gov (United States)

    Sakamoto, T.; McCormick, S.D.

    2006-01-01

    Prolactin is an important regulator of multiple biological functions in vertebrates, and has been viewed as essential to ion uptake as well as reduction in ion and water permeability of osmoregulatory surfaces in freshwater and euryhaline fish. Prolactin-releasing peptide seems to stimulate prolactin expression in the pituitary and peripheral organs during freshwater adaptation. Growth hormone, a member of the same family of hormones as prolactin, promotes acclimation to seawater in several teleost fish, at least in part through the action of insulin-like growth factor I. In branchial epithelia, development and differentiation of the seawater-type chloride cell (and their underlying biochemistry) is regulated by GH, IGF-I, and cortisol, whereas the freshwater-type chloride cell is regulated by prolactin and cortisol. In the epithelia of gastrointestinal tract, prolactin induces cell proliferation during freshwater adaptation, whereas cortisol stimulates both cell proliferation and apoptosis. We propose that control of salinity acclimation in teleosts by prolactin and growth hormone primarily involves regulation of cell proliferation, apoptosis, and differentiation (the latter including upregulation of specific ion transporters), and that there is an important interaction of these hormones with corticosteroids. ?? 2005 Elsevier Inc. All rights reserved.

  3. Principles of the prolactin/vasoinhibin axis.

    Science.gov (United States)

    Triebel, Jakob; Bertsch, Thomas; Bollheimer, Cornelius; Rios-Barrera, Daniel; Pearce, Christy F; Hüfner, Michael; Martínez de la Escalera, Gonzalo; Clapp, Carmen

    2015-11-15

    The hormonal family of vasoinhibins, which derive from the anterior pituitary hormone prolactin, are known for their inhibiting effects on blood vessel growth, vasopermeability, and vasodilation. As pleiotropic hormones, vasoinhibins act in multiple target organs and tissues. The generation, secretion, and regulation of vasoinhibins are embedded into the organizational principle of an axis, which integrates the hypothalamus, the pituitary, and the target tissue microenvironment. This axis is designated as the prolactin/vasoinhibin axis. Disturbances of the prolactin/vasoinhibin axis are associated with the pathogenesis of retinal and cardiac diseases and with diseases occurring during pregnancy. New phylogenetical, physiological, and clinical implications are discussed.

  4. Suppression of prolactin signaling by pyrrolidine dithiocarbamate is alleviated by N-acetylcysteine in mammary epithelial cells.

    Science.gov (United States)

    Wang, Jen-Hsing; Du, Jyun-Yi; Wu, Yi-Ying; Chen, Meng-Chi; Huang, Chun-Hao; Shen, Hsin-Ju; Lee, Chin-Feng; Lin, Ting-Hui; Lee, Yi-Ju

    2014-09-05

    Prolactin is the key hormone to stimulate milk synthesis in mammary epithelial cells. It signals through the Jak2-Stat5 pathway to induce the expression of β-casein, a milk protein which is often used as a marker for mammary differentiation. Here we examined the effect of pyrrolidine dithiocarbamate (PDTC) on prolactin signaling. Our results show that PDTC downregulates prolactin receptor levels, and inhibits prolactin-induced Stat5 tyrosine phosphorylation and β-casein expression. This is not due to its inhibitory action on NF-κB since application of another NF-κB inhibitor, BAY 11-7082, and overexpression of I-κBα super-repressor do not lead to the same results. Instead, the pro-oxidant activity of PDTC is involved as inclusion of the antioxidant N-acetylcysteine restores prolactin signaling. PDTC triggers great extents of activation of ERK and JNK in mammary epithelial cells. These do not cause suppression of prolactin signaling but confer serine phosphorylation of insulin receptor substrate-1, thereby perturbing insulin signal propagation. As insulin facilitates optimal β-casein expression, blocking insulin signaling by PDTC might pose additional impediment to β-casein expression. Our results thus imply that lactation will be compromised when the cellular redox balance is dysregulated, such as during mastitis.

  5. 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.

  6. Discovery of the improved antagonistic prolactin variants by library screening.

    Science.gov (United States)

    Liu, Yun; Gong, Wei; Breinholt, Jens; Nørskov-Lauritsen, Leif; Zhang, Jinchao; Ma, Qinhong; Chen, Jianhe; Panina, Svetlana; Guo, Wei; Li, Tengkun; Zhang, Jingyuan; Kong, Meng; Liu, Zibing; Mao, Jingjing; Christensen, Leif; Hu, Sean; Wang, Lingyun

    2011-11-01

    Prolactin (PRL), a potent growth stimulator of the mammary epithelium, has been suggested to be a factor contributing to the development and progression of breast and prostate cancer. Several PRL receptor (PRLR) antagonists have been identified in the past decades, but their in vivo growth inhibitory potency was restricted by low receptor affinity, rendering them pharmacologically unattractive for clinical treatment. Thus, higher receptor affinity is essential for the development of improved PRLR antagonistic variants with improved in vivo potency. In this study, we generated Site 1 focused protein libraries of human G129R-PRL mutants and screened for those with increased affinity to the human PRLR. By combining the mutations with enhanced affinities for PRLR, we identified a novel G129R-PRL variant with mutations at Site 1 that render nearly 50-fold increase in the antagonistic potency in vitro.

  7. 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.

  8. [Interest in prolactin levels in galactorrhea].

    Science.gov (United States)

    Bessioud, Moncef; Mamlouk, Lilia; Djait, Riadh; Ben Aïssa, Rim; Gueddana, Nésiha

    2004-02-01

    The action of prolactin (PRL) in supra-physiological levels on the ovaries or on the hypothalamic-pituitary axis for the release of gonadotropins leads to a reversible inhibition of the cyclic functioning of the pituitary gland and of the ovaries. The consequences are either the production of immature follicles marked by anovulatory or dysovulatory cycles, or the absence of follicle production marked by amenorrhea. Thus, prolactin plays a major role in the productive system by its lactotropic and antigonadotropic effects. Through this study we intend to try to determine the diagnostic value of the association of the cyclic dysfunctions with galactorrhea by measuring the prolactin levels in 2236 patients complaining of galactorrhea. Measurements of FSH and LH levels were also performed in 236 women among those consulting for infertility associated with galactorrhea. The results obtained showed that galactorrhea was associated with prolactenemia in only 17% of cases and of the ovaries was proportional to the prolactin in blood.

  9. Episodic evolution of prolactin gene in primates

    Institute of Scientific and Technical Information of China (English)

    LI Ying; DUAN Ziyuan; JIA Lu; ZHANG Yaping

    2005-01-01

    In the present study, we obtained exon 2―5 of prolactin (PRL) gene from four primate species by PCR and sequencing. Adding other genes available in GenBank, we calculate amino acid substitution rates for prolactin gene in primate. Comparison of nonsynonymous substitution rate to synonymous substitution rate ratios shows no evidence of positive selection for any lineage of primate prolactin gene. According to this and the facts that (I) no sites under positive selection are inferred by using maximum-likelihood method; (ii) among 32 amino acid replacement that occurred along the rapid evolutionary phase, only two are included in the 40 functionally important residues, indicating that amino acid replacement tends to occur in those functionally unimportant residues; (iii) partial of prolactin function is replaced by placental lactogen in primate at the rapid evolutionary phase of prolactin gene, we thus deem that it is relaxation of purifying selection to some extent rather than positive selection that enforces the rapid evolution of primate prolactin gene.

  10. [Prolactin as a modulator of antiparasitic immunity].

    Science.gov (United States)

    Płociński, Przemysław; Dzitko, Katarzyna; Długońska, Henryka

    2007-01-01

    Prolactin (PRL) is a polypeptide hormone of the pituitary origin, that expresses over 300 separate biological activities, including its involvement in the regulation of immune functions. The hormone's immune capacities are related, among others, to comitogenic activity, prevention of immune cell apoptosis, stimulation of interleukins and antibodies production. Prolactin acts as a potent positive modulator of immunity to some protozoan parasites. It is well established that the hormone stimulates IFN-gamma and many other TH1-type cytokines production during Toxoplasma gondii, Leishmania sp. and Acanthamoeba castellanii infections. Recent studies suggest that human prolactin may be a regulator of antiparasitic activity against Plasmodium falciparum. On the other hand pregnancy-associated hyperprolactinemia may have a relevant contribution to reactivation of latent infections caused by many helminthic parasites, like Ancylostoma sp. or Necator sp. It is possibly connected with the process of transmammary transmission of hookworm infection to breast-fed newborns. Moreover, an increase in endogenous circulating prolactin during late pregnancy and lactation in ewes infected with Haemonchus contortus, promotes the phenomenon of periparturient egg rise. High prolactin levels have also been seen in dairy cattle suffering from other trichostrongylids infections. In this article we have discussed the role of prolactin as an important regulator of immunity to parasites.

  11. Interferon Beta-1b Injection

    Science.gov (United States)

    ... medications (Avonex, Plegridy, Rebif), any other medications, human albumin, mannitol, or any of the other ingredients in ... 1b powder at room temperature and away from excess heat and moisture (not in the bathroom). If ...

  12. Extra-pituitary prolactin (PRL) and prolactin-like protein (PRL-L) in chickens and zebrafish.

    Science.gov (United States)

    Bu, Guixian; Liang, Xiaomeng; Li, Juan; Wang, Yajun

    2015-09-01

    It is generally believed that in vertebrates, prolactin (PRL) is predominantly synthesized and released by pituitary lactotrophs and plays important roles in many physiological processes via activation of PRL receptor (PRLR), including water and electrolyte balance, reproduction, growth and development, metabolism, immuno-modulation, and behavior. However, there is increasing evidence showing that PRL and the newly identified 'prolactin-like protein (PRL-L)', a novel ligand of PRL receptor, are also expressed in a variety of extra-pituitary tissues, such as the brain, skin, ovary, and testes in non-mammalian vertebrates. In this brief review, we summarize the recent research progress on the structure, biological activities, and extra-pituitary expression of PRL and PRL-L in chickens (Gallus gallus) and zebrafish (Danio rerio) from our and other laboratories and briefly discuss their potential paracrine/autocrine roles in non-mammalian vertebrates, which may promote us to rethink the broad spectrum of PRL actions previously attributed to pituitary PRL only.

  13. 催乳素受体基因多态性及其与部分山羊品种产羔数关系%Polymorphism of Prolactin Receptor Gene and Its Relationship with Litter Size of Some Goat Breeds

    Institute of Scientific and Technical Information of China (English)

    储明星; 张跟喜; 王金玉; 方丽; 叶素成

    2008-01-01

    催乳素(prolactin,PRL)是一种垂体前叶肽类激素,PRL的所有功能都由催乳素受体(prolactin receptor,PRLR)调节。本研究采用单链构象多态(single strand conformation polymorphism,SSCP)方法检测PRLR基因外显子3至外显子9和内含子9在高繁殖力山羊品种(济宁青山羊)和低繁殖力山羊品种(辽宁绒山羊和安哥拉山羊)中的多态性,

  14. Association between dopamine-related polymorphisms and plasma concentrations of prolactin during risperidone treatment in schizophrenic patients.

    Science.gov (United States)

    Yasui-Furukori, Norio; Saito, Manabu; Tsuchimine, Shoko; Nakagami, Taku; Sato, Yasushi; Sugawara, Norio; Kaneko, Sunao

    2008-08-01

    Hyperprolactinemia is an inevitable consequence of treatment with antipsychotic agents to some extent because prolactin response to antipsychotics is related to dopamine blockade. Recent studies have suggested that polymorphisms of the dopamine receptors are associated with therapeutic response to antipsychotics. Thus, we studied the effects of major polymorphisms of dopamine-related genes on plasma concentration of prolactin. Subjects were 174 schizophrenic patients (68 males, 106 females) receiving 3 mg twice daily of risperidone for at least 4 weeks. Sample collections were conducted 12 h after the bedtime dosing. Five dopamine-related polymorphisms (Taq1A, -141C ins/del for DRD2, Ser9Gly for DRD3, 48 bp VNTR for DRD4, Val158Met for COMT) were identified. The mean (+/-SD) plasma concentration of prolactin in females was significantly higher than males (54.3+/-27.2 ng/ml versus 126.8+/-70.2 ng/ml, p<0.001). No dopamine-related polymorphisms differed the plasma concentration of prolactin in males or females. Multiple regression analyses including plasma drug concentration and age revealed that plasma concentration of prolactin correlated with gender (standardized partial correlation coefficients (beta)=0.551, p<0.001) and negatively with age (standardized beta=-0.202, p<0.01). No correlations were found between prolactin concentration and dopamine-related polymorphisms. These findings suggest that plasma prolactin concentrations in females are much higher than in males but the dopamine-related variants are not predominantly associated with plasma concentration of prolactin.

  15. 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.

  16. Hypergravity induced prolactin surge in female rats

    Science.gov (United States)

    Megory, E.; Oyama, J.

    1985-01-01

    Acute initial exposure to hypergravity (HG) was previously found to induce prolonged diestrous in rats, which was followed by return to normal estrous cycling upon more prolonged exposure to continuous HG. Bromergocryptine was found to prevent this prolonged diestrous. In this study it is found that in female rats 20 h of 3.14 G exposure (D-1 1200 h until D-2 0800 h) can induce prolactin surge at D-2 1600 h. Shorter exposure time (8 h), or exposure during a different part of the estrous cycle (19 h: from D-1 0700 h until D-2 0200 h) could not elicit this prolactin surge. Similar exposure of male rats of HG did not alter significantly their prolactin levels. It is possible that the hypothalamus of male and female rats responds differently to stimulation by HG.

  17. 斜带石斑鱼(Epinephelus coioides)两种催乳素受体基因的cDNA克隆和mRNA表达分析%cDNAs CLONING AND mRNA EXPRESSION OF TWO PROLACTIN RECEPTORS IN ORANGE-SPOTTED GROUPER EPINEPHELUS COIOIDES

    Institute of Scientific and Technical Information of China (English)

    张勇; 马细兰; 陈勇智; 李水生; 陈华谱; 刘晓春; 林浩然

    2012-01-01

    Prolactin (PRL) has many important physiological roles in the control of growth, osmoregulation and reproduction, which is mediated by prolactin receptor (PRLR). In this study, two cDNAs encoding PRLR were isolated from the gill of orange-spotted grouper Epinephelus coioides. The two cDNAs, one consisting of 1947bp and the other of 1749bp, encoding for putative 649- and 487-amino acid PRLR (designated PRLR1 and PRLR2, respectively), shared 40.4% identity in deduced amino acid sequence. PRLR1 and PRLR2 showed the conserved structural characteristics of PRLR family, including the WS motif, the box1 region, extracellular cysteine residues and intracellular tyrosine residues. However, there were differences of structural features between the two receptors as well. PRLR1 has 13 intracellular tyrosine residues while PRLR2 only has 8. The structural discrepancies thus undoubtedly indicated the distinct biological functions of PRLR1 and PRLR2. Real-time RT-PCR analysis showed that both PRLR1 and PRLR2 mRNAs were presented in all tissues tested and expressed extremely highly in gill, kidney and intestine, lowly in pituitary and hypothalamus. The expressions of PRLR1 and PRLR2 in different embryo developmental stages were also detected by real-time PCR. The strongest signal was detected in the fertilized egg stage for PRLR1, while in the stage of optic vesicle and smoite formation for PRLR2. The expression level of PRLR2 is much higher than PRLR1 in all stages examined except in the fertilized egg stage. The expression distinction of PRLR1 and PRLR2 suggested that they may play different roles during early development of orange-spotted grouper.%采用RT-PCR方法克隆了斜带石斑鱼两种催乳素受体(Prolactin receptor,PRLR)的cDNA序列,序列分析表明:PRLR1开放阅读框为1947bp,共编码649个氨基酸,PRLR2开放阅读框为1749bp,共编码487个氨基酸,PRLR1与PRLR2的氨基酸同源性为40.4%。用Real-time RT-PCR方法研究了PRLR1

  18. Prolactin response to low dose sulpiride.

    OpenAIRE

    1987-01-01

    1 Prolactin levels in response to sulpiride were studied in healthy volunteers. 2 Oral doses of 1 mg-50 mg sulpiride or placebo were given. 3 A 3 mg sulpiride dose produced similar levels to those achieved with both 10 mg and 50 mg. 4 Circadian effects were studied showing no significant differences in the prolactin response to sulpiride. 5 Acute or chronic responses showed an attenuation with chronic sulpiride treatment to 50% of the peak levels attained with acute treatment. 6 These results...

  19. The brain decade in debate: VIII. Peptide hormones and behavior: cholecystokinin and prolactin

    Directory of Open Access Journals (Sweden)

    M.C. Beinfeld

    2001-11-01

    Full Text Available This article is a transcription of an electronic symposium held on November 28, 2000 in which active researchers were invited by the Brazilian Society of Neuroscience and Behavior (SBNeC to discuss the advances of the last decade in the peptide field with particular focus on central actions of prolactin and cholecystokinin. The comments in this symposium reflect the diversity of prolactin and cholecystokinin research and demonstrate how the field has matured. Since both peptides play a role in reproductive behaviors, particularly mother-infant interactions, this was the starting point of the discussion. Recent findings on the role of the receptor subtypes as well as interaction with other peptides in this context were also discussed. Another issue discussed was the possible role of these peptides in dopamine-mediated rewarding systems. Both prolactin and cholecystokinin are involved in mechanisms controlling food intake and somatic pain thresholds. The role of peripheral inputs through vagal afferents modulating behavior was stressed. The advent of knockout animals as potential generators of new knowledge in this field was also addressed. Finally, interactions with other neuropeptides and investigation of the role of these peptides in other fields such as immunology were mentioned. Knowledge about the central functions of prolactin and cholecystokinin has shown important advances. The role of these peptides in neurological and psychiatric syndromes such as anorexia, drug abuse and physiological disturbances that lead to a compromised maternal behavior seems relevant.

  20. Prolactin genomics and biology in herbivores

    Science.gov (United States)

    Circulating prolactin concentrations are typically reduced in animals suffering from tall fescue toxicosis, and have become a standard biological marker for tall fescue toxicosis. Wild-type endophyte infestations of tall fescue pastures result in forage containing ergot alkaloids. Ergot alkaloids ...

  1. 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

  2. Endogenous prolactin generated during peripheral inflammation contributes to thermal hyperalgesia.

    Science.gov (United States)

    Scotland, Phoebe E; Patil, Mayur; Belugin, Sergei; Henry, Michael A; Goffin, Vincent; Hargreaves, Kenneth M; Akopian, Armen N

    2011-09-01

    Prolactin (PRL) is a hormone and a neuromodulator. It sensitizes TRPV1 (transient receptor potential cation channel subfamily V member 1) responses in sensory neurons, but it is not clear whether peripheral inflammation results in the release of endogenous PRL, or whether endogenous PRL is capable of acting as an inflammatory mediator in a sex-dependent manner. To address these questions, we examined inflammation-induced release of endogenous PRL, and its regulation of thermal hyperalgesia in female and male rats. PRL is expressed in several types of peripheral neuronal and non-neuronal cells, including TRPV1-positive nerve fibers, preadipocytes and activated macrophages/monocytes localized in the vicinity of nerves. Evaluation of PRL levels in hindpaws and plasma indicated that complete Freund's adjuvant (CFA) stimulates release of peripheral, but not systemic, PRL within 6-48 h in both ovariectomized females with estradiol replacement (OVX-E) and intact male rats. The time course of release varies in OVX-E and intact male rats. We next employed the prolactin receptor (PRL-R) antagonist Δ1-9-G129R-hPRL to assess the role of locally produced PRL in nociception. Applied at a ratio of 1 : 1 (PRL:Δ1-9-G129R-hPRL; 40 nm each), this antagonist was able to nearly (≈ 80%) reverse PRL-induced sensitization of capsaicin responses in rat sensory neurons. CFA-induced inflammatory thermal hyperalgesia in OVX-E rat hindpaws was significantly reduced in a dose-dependent manner by the PRL-R antagonist at 6 h but not at 24 h. In contrast, PRL contributed to inflammatory thermal hyperalgesia in intact male rats at 24, but not at 6 h. These findings indicate that inflammation leads to accumulation of endogenous PRL in female and male rats. Furthermore, PRL acts as an inflammatory mediator at different time points for female and intact male rats.

  3. Histaminergic regulation of prolactin secretion

    DEFF Research Database (Denmark)

    Knigge, U P

    1990-01-01

    of DA synthesis and of DA or serotonin (5-HT) receptors inhibit or prevent the PRL stimulatory action of HA infused centrally or systemically. However, other factors regulating PRL secretion (e.g. beta-endorphin, vasoactive intestinal peptide, vasopressin or TRH) may be involved in the mediation...

  4. Migratory fat deposition in European quail: a role for prolactin?

    Science.gov (United States)

    Boswell, T; Sharp, P J; Hall, M R; Goldsmith, A R

    1995-07-01

    The present study addresses the role of prolactin as a regulator of migratory fattening in European quail (Coturnix coturnix). Plasma prolactin levels in captive birds undergoing migratory fattening in an outdoor aviary and in the laboratory were measured by radioimmunoassay with an antibody raised against recombinant-derived chicken prolactin. No strong association between prolactin and migratory fattening was apparent, and prolactin levels were more closely related to daylength, with the highest concentrations being reached on long days. Plasma prolactin profiles were similar in intact and castrated male quail. Prolactin was secreted in a daily rhythm, with the highest concentrations occurring early in the photophase. However, when birds were food-restricted for 50 days during a migratory phase, there was no difference in fat deposition between birds food-deprived for the first half of the daily photophase compared with those deprived for the second half. Fattening was reduced in the food-restricted birds relative to ad libitum-fed controls, but there was no difference in plasma prolactin levels between the groups. Injections of ovine prolactin (4 mg/kg) significantly increased food intake and body mass of birds maintained on long days, but there were no differences in fattening between birds injected in the morning compared with those injected in the afternoon. Collectively, these results do not support a major role for prolactin in the regulation of migratory fat deposition in European quail.

  5. Prolactin in the Afrotheria: characterization of genes encoding prolactin in elephant (Loxodonta africana), hyrax (Procavia capensis) and tenrec (Echinops telfairi).

    Science.gov (United States)

    Wallis, Michael

    2009-02-01

    Pituitary prolactin shows an episodic pattern of molecular evolution, with occasional short bursts of rapid change imposed on a generally rather slow evolutionary rate. In mammals, episodes of rapid change occurred in the evolution of primates, cetartiodactyls, rodents and the elephant. The bursts of rapid evolution in cetartiodactyls and rodents were followed by duplications of the prolactin gene that gave rise to large families of prolactin-related proteins including placental lactogens, while in primates the burst was followed by corresponding duplications of the related GH gene. The position in elephant is less clear. Extensive data relating to the genomic sequences of elephant and two additional members of the group Afrotheria are now available, and have been used here to characterize the prolactin genes in these species and explore whether additional prolactin-related genes are present. The results confirm the rapid evolution of elephant (Loxodonta africana) prolactin - the sequence of elephant prolactin is substantially different from that predicted for the ancestral placental mammal. Hyrax (Procavia capensis) prolactin is even more divergent but tenrec (Echinops telfairi) prolactin is strongly conserved. No evidence was obtained from searches of public databases for additional genes encoding prolactin-like proteins in any of these species. Detailed analysis of evolutionary rates, and other factors, indicates that the episode of rapid change in hyrax, and probably elephant, was adaptive, though the nature of the associated biological change(s) is not clear.

  6. Cysteamine depletes prolactin in young and old hyperprolactinemic rats

    Energy Technology Data Exchange (ETDEWEB)

    Simpkins, J.W.; Estes, K.S.; Millard, W.J.; Sagar, S.M.; Martin, J.B.

    1983-05-01

    Studies were undertaken to evaluate the effects of cysteamine on serum and anterior pituitary concentrations of prolactin in hyperprolactinemic female rats. Serum prolactin was elevated in young (4 to 5 months old) rats by implantation of 17 beta-estradiol while 26- to 28-month-old rats were in constant estrus and exhibited an age-related hyperprolactinemia. At 4 h after treatment with cysteamine (90 mg/kg body wt) serum and anterior pituitary prolactin concentrations were reduced in young animals by 98 and 85%, respectively. In old constant-estrous rats, cysteamine reduced serum prolactin by 92% and anterior pituitary prolactin by 82%. In young pseudopregnant rats, cysteamine induced a prompt resumption of estrous cycles. These studies indicate that cysteamine is an effective depletor of serum and pituitary prolactin in hyperprolactinemic rats.

  7. Prolactin and aggression in women with fertility problems.

    Science.gov (United States)

    Barry, J A; Moran, E; Parekh, H S; Morewood, T; Thomas, M; Hardiman, P J

    2014-10-01

    This study tested the hypothesis that women with higher prolactin feel more hostility, anger and aggression. A total of 66 women with moderate fertility problems were grouped into the 50% who had the highest and the 50% who had the lowest levels of prolactin. Levels of hostility, aggression and anger were compared. Women with higher prolactin levels did not report significantly increased hostility. After Bonferroni correction, women with lower prolactin showed non-significantly increased scores on two measures of state anger, and on a measure of trait temper. When comparing those with the highest and lowest 20% of prolactin levels, those with lower prolactin had non-significantly higher scores on trait temper and outward expression of anger, and non-significantly lower scores for control of anger. Although non-significant, these findings run counter to those of earlier studies on this topic. Implications for future research and patient care are discussed.

  8. The role of prolactin in fish reproduction.

    Science.gov (United States)

    Whittington, Camilla M; Wilson, Anthony B

    2013-09-15

    Prolactin (PRL) has one of the broadest ranges of functions of any vertebrate hormone, and plays a critical role in regulating aspects of reproduction in widely divergent lineages. However, while PRL structure, mode of action and functions have been well-characterised in mammals, studies of other vertebrate lineages remain incomplete. As the most diverse group of vertebrates, fish offer a particularly valuable model system for the study of the evolution of reproductive endocrine function. Here, we review the current state of knowledge on the role of prolactin in fish reproduction, which extends to migration, reproductive development and cycling, brood care behaviour, pregnancy, and nutrient provisioning to young. We also highlight significant gaps in knowledge and advocate a specific bidirectional research methodology including both observational and manipulative experiments. Focusing research efforts towards the thorough characterisation of a restricted number of reproductively diverse fish models will help to provide the foundation necessary for a more explicitly evolutionary analysis of PRL function.

  9. Decreased prolactin response to hypoglycaemia in patients with rheumatoid arthritis: correlation with disease activity.

    NARCIS (Netherlands)

    Eijsbouts, A.M.M.; Hoogen, F.H.J. van den; Laan, R.F.J.M.; Sweep, C.G.J.; Hermus, A.R.M.M.; Putte, L.B.A. van de

    2005-01-01

    OBJECTIVE: To compare basal and stimulated prolactin levels between patients with rheumatoid arthritis and healthy controls, and to assess the effects of antirheumatic treatment on prolactin concentrations. METHODS: Serum prolactin was assessed under basal conditions and during an insulin tolerance

  10. Association study of functional polymorphisms in interleukins and interleukin receptors genes: IL1A, IL1B, IL1RN, IL6, IL6R, IL10, IL10RA and TGFB1 in schizophrenia in Polish population.

    Science.gov (United States)

    Kapelski, Pawel; Skibinska, Maria; Maciukiewicz, Malgorzata; Wilkosc, Monika; Frydecka, Dorota; Groszewska, Agata; Narozna, Beata; Dmitrzak-Weglarz, Monika; Czerski, Piotr; Pawlak, Joanna; Rajewska-Rager, Aleksandra; Leszczynska-Rodziewicz, Anna; Slopien, Agnieszka; Zaremba, Dorota; Twarowska-Hauser, Joanna

    2015-12-01

    Schizophrenia has been associated with a large range of autoimmune diseases, with a history of any autoimmune disease being associated with a 45% increase in risk for the illness. The inflammatory system may trigger or modulate the course of schizophrenia through complex mechanisms influencing neurodevelopment, neuroplasticity and neurotransmission. In particular, increases or imbalance in cytokine before birth or during the early stages of life may affect neurodevelopment and produce vulnerability to the disease. A total of 27 polymorphisms of IL1N gene: rs1800587, rs17561; IL1B gene: rs1143634, rs1143643, rs16944, rs4848306, rs1143623, rs1143633, rs1143627; IL1RN gene: rs419598, rs315952, rs9005, rs4251961; IL6 gene: rs1800795, rs1800797; IL6R gene: rs4537545, rs4845617, rs2228145, IL10 gene: rs1800896, rs1800871, rs1800872, rs1800890, rs6676671; IL10RA gene: rs2229113, rs3135932; TGF1B gene: rs1800469, rs1800470; each selected on the basis of molecular evidence for functionality, were investigated in this study. Analysis was performed on a group of 621 patients with diagnosis of schizophrenia and 531 healthy controls in Polish population. An association of rs4848306 in IL1B gene, rs4251961 in IL1RN gene, rs2228145 and rs4537545 in IL6R with schizophrenia have been observed. rs6676671 in IL10 was associated with early age of onset. Strong linkage disequilibrium was observed between analyzed polymorphisms in each gene, except of IL10RA. We observed that haplotypes composed of rs4537545 and rs2228145 in IL6R gene were associated with schizophrenia. Analyses with family history of schizophrenia, other psychiatric disorders and alcohol abuse/dependence did not show any positive findings. Further studies on larger groups along with correlation with circulating protein levels are needed.

  11. Reproduction and energy balance: the integrative role of prolactin

    OpenAIRE

    T I Romantsova

    2014-01-01

    The physiological mechanisms controlling reproduction are closely linked to energy balance. In the recent years, accumulating evidence suggests that prolactin regulates metabolic functions, besides regulating breast development and stimulating milk formation. Hyperprolactinemia is associated with obesity and treatment with dopamine agonists results in weight loss. We discuss the integrated effects of prolactin in the metabolic control and reproductive function, the role of prolactin in the pa...

  12. 60 YEARS OF NEUROENDOCRINOLOGY: The hypothalamo-prolactin axis

    OpenAIRE

    Grattan, David R.

    2015-01-01

    The hypothalamic control of prolactin secretion is different from other anterior pituitary hormones, in that it is predominantly inhibitory, by means of dopamine from the tuberoinfundibular dopamine neurons. In addition, prolactin does not have an endocrine target tissue, and therefore lacks the classical feedback pathway to regulate its secretion. Instead, it is regulated by short loop feedback, whereby prolactin itself acts in the brain to stimulate production of dopamine and thereby inhibi...

  13. 60 YEARS OF NEUROENDOCRINOLOGY: The hypothalamo-prolactin axis.

    Science.gov (United States)

    Grattan, David R

    2015-08-01

    The hypothalamic control of prolactin secretion is different from other anterior pituitary hormones, in that it is predominantly inhibitory, by means of dopamine from the tuberoinfundibular dopamine neurons. In addition, prolactin does not have an endocrine target tissue, and therefore lacks the classical feedback pathway to regulate its secretion. Instead, it is regulated by short loop feedback, whereby prolactin itself acts in the brain to stimulate production of dopamine and thereby inhibit its own secretion. Finally, despite its relatively simple name, prolactin has a broad range of functions in the body, in addition to its defining role in promoting lactation. As such, the hypothalamo-prolactin axis has many characteristics that are quite distinct from other hypothalamo-pituitary systems. This review will provide a brief overview of our current understanding of the neuroendocrine control of prolactin secretion, in particular focusing on the plasticity evident in this system, which keeps prolactin secretion at low levels most of the time, but enables extended periods of hyperprolactinemia when necessary for lactation. Key prolactin functions beyond milk production will be discussed, particularly focusing on the role of prolactin in inducing adaptive responses in multiple different systems to facilitate lactation, and the consequences if prolactin action is impaired. A feature of this pleiotropic activity is that functions that may be adaptive in the lactating state might be maladaptive if prolactin levels are elevated inappropriately. Overall, my goal is to give a flavour of both the history and current state of the field of prolactin neuroendocrinology, and identify some exciting new areas of research development.

  14. Symptoms of hyperprolactinemia with normal serum prolactin: is treatment required?

    Directory of Open Access Journals (Sweden)

    Deepti Verma

    2016-06-01

    Full Text Available Galactorrhea with menstrual abnormalities like oligomenorrhea or amenorrhea point towards a provisional diagnosis of increased serum prolactin levels or hyperprolactinemia. However, as the prolactin hormone is heterogeneous with two forms- the bioactive and the immunoactive forms, patients can have all the features of hyperprolactinemia with normal serum prolactin levels. [Int J Reprod Contracept Obstet Gynecol 2016; 5(6.000: 2041-2042

  15. THE COMPARATIVE EXPRESSION AND CROSS-INTERACTIONS OF GROWTH HORMONE/PROLACTIN LIGAND AND RECEPTOR FAMILY MEMBERS IN ZEBRAFISH EARLY EMBRYOS%生长激素/催乳素家族配体和受体成员在斑马鱼早期胚胎中的表达比较和交叉活性分析

    Institute of Scientific and Technical Information of China (English)

    于力群; 王厚鹏; 朱作言; 孙永华

    2014-01-01

    Growth hormone (GH) is a member of the GH/Prolactin (PRL) protein super family. It is secreted by anterior pituitary and critically involved in the regulation of cell proliferation, differentiation and migration. Using RT-PCR (re-verse-transcription PCR), our previous study revealed that both gh and its receptor gene ghra (growth hormone receptor a) were maternally expressed in zebrafish. This suggested that the GH/GHR signaling pathway might play an important role at the early stage of zebrafish development. To further study the function of GH/PRL signaling pathway in zebrafish embryogenesis, here we characterized and compared the expression patterns of gh/prl and their receptor family members in early embryonic development using real-time PCR and in situ hybridization. We found that the ligand family mem-bers, gh and somatolactin (smtl), and the receptor gene family members, ghra and ghrb, were maternally expressed in zebrafish. The analysis of spi2.1 promoter activity indicated the cross-interaction between various ligand family mem-bers and GHRa in the early embryos of zebrafish. Our results demonstrated the important role of the GH/PRL family signaling pathway in the early development of zebrafish.%为了进一步研究 GH/PRL 家族信号通路在鱼类早期胚胎发育中的作用,研究以斑马鱼为模型,通过Real-time PCR技术和原位杂交技术刻画并比较了GH/PRL家族成员及其受体家族成员在胚胎发育早期的表达模式。结果发现,在配体家族成员中,生长激素(Growth hormone, GH)和生长催乳素(Somatolactin, smtl)存在母源表达,在受体家族成员中, ghra、ghrb存在母源表达。利用荧光素酶分析spi2.1启动子活性的结果初步证明,在斑马鱼早期胚胎发育中,各配体家族成员与GHRa之间可以发生广泛的互作。这一系列结果对于我们认识GH/PRL家族信号通路在斑马鱼早期发育中的作用具有重要的指导意义。

  16. The effects of immersion and exercise on prolactin during pregnancy.

    Science.gov (United States)

    Katz, V L; McMurray, R; Turnbull, C D; Berry, M; Bowman, C; Cefalo, R C

    1990-01-01

    Prolactin is an important hormone during pregnancy, affecting mother, fetus, and amniotic fluid volume. Immersion is known to affect prolactin levels significantly. To determine the effect of immersion and exercise on the prolactin response during pregnancy, we examined serum prolactin levels at 15, 25, and 35 weeks' gestation and 10 weeks post partum. Twelve women completed 20 min land rest, 20 min immersion in 30 degrees C water to the xiphoid, and 20 min exercise in the water at 60% VO2max. Resting prolactin levels were 1.91 +/- 0.32, 4.55 +/- 0.5, and 5.85 +/- 0.27 nmol.l-1 +/- standard error of the mean at 15, 25, and 35 weeks' gestation, respectively. Postpartum lactating women had a resting mean prolactin level of 3.95 +/- 1.6 versus 0.22 +/- 0.4 nmol.l-1 in non-lactating women. Prolactin levels declined significantly during immersion even after correction for dilution by plasma volume shifts. The immersion response was inversely related to the duration of pregnancy with 29%, 22%, and 12% drops during 15-, 25- and 35-week trials, respectively. Compared to rest, exercise prolactin levels remained depressed during the 15th and 25th week trials. We hypothesize that immersion in water caused prolactin levels to decline.

  17. Improvement in neurological outcome and abolition of cerebrovascular endothelin B and 5-hydroxytryptamine 1B receptor upregulation through mitogen-activated protein kinase kinase 1/2 inhibition after subarachnoid hemorrhage in rats

    DEFF Research Database (Denmark)

    Larsen, Carl Christian; Povlsen, Gro Klitgaard; Rasmussen, Marianne Nelly Paola;

    2011-01-01

    Delayed cerebral ischemia after subarachnoid hemorrhage (SAH) remains a major cause of death and disability. It has been hypothesized that cerebrovascular upregulation of vasoconstrictor receptors is a key step in the development of delayed cerebral ischemia. Upregulation of endothelin-B (ET(B)) ...

  18. Main: 1B37 [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B37 トウモロコシ Corn Zea mays L. Polyamine Oxidase Precursor Name=Pao; Zea Mays Molecul...FSNWPVGVNRYEYDQLRAPVGRVYFTGEHTSEHYNGYVHGAYLSGIDSAEILINCAQKKMCKYHVQGKYD corn_1B37.jpg ...

  19. 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

  20. The Association Analysis of Prolactin Receptor Gene Polymorphisms with Milk Yield in Yili Horse%伊犁马催乳素受体基因的遗传多态性及其与产奶量的关联分析

    Institute of Scientific and Technical Information of China (English)

    于茜; 臧长江; 刘玲玲; 马海玉; 何美升; 姜鑫; 曹行; 刘武军

    2015-01-01

    试验旨在研究伊犁马催乳素受体(prolactin receptor,PRLR)基因多态性及其与产奶量之间的关联性.以60匹伊犁马为研究对象,选取PRLR基因侧翼区的部分片段,采用PCR SSCP技术检测其遗传多态性,并与伊犁马的日产奶量进行关联分析,研究PRLR基因的多态性与伊犁马产奶性能的关系.结果显示,PRLR基因侧翼区的2个片段均具有多态性,都存在3种基因型:AA、AB和BB,测序结果显示PRLR P1的碱基突变位置为g.29764513 G>A,该突变为错义突变,导致其编码的氨基酸由组氨酸变成精氨酸,经关联分析发现,该突变对伊犁马口产奶量有显著影响(P<0.05);PRLR-P2的碱基突变位置为g,30106804 C>A,该突变为同义突变,未导致其编码的氨基酸发生改变,经关联分析发现,该突变对伊犁马日产奶量有显著影响(P<0.05).伊犁马PRLR基因侧翼区的碱基突变与日产奶量之间存在关联性,且可能是影响伊犁马产奶性能的重要位点.

  1. 18 CFR 1b.12 - Transcripts.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Transcripts. 1b.12 Section 1b.12 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.12 Transcripts. Transcripts, if any,...

  2. 18 CFR 1b.14 - Subpoenas.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Subpoenas. 1b.14 Section 1b.14 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.14 Subpoenas. (a) Service of a...

  3. 18 CFR 1b.19 - Submissions.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Submissions. 1b.19 Section 1b.19 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.19 Submissions. In the event...

  4. 18 CFR 1b.5 - Formal investigations.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Formal investigations. 1b.5 Section 1b.5 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.5 Formal investigations....

  5. 18 CFR 1b.6 - Preliminary investigations.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Preliminary investigations. 1b.6 Section 1b.6 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.6 Preliminary investigations....

  6. 18 CFR 1b.1 - Definitions.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Definitions. 1b.1 Section 1b.1 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.1 Definitions. For purposes of this part—...

  7. 18 CFR 1b.2 - Scope.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Scope. 1b.2 Section 1b.2 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.2 Scope. This part applies to...

  8. High-calcium diet modulates effects of long-term prolactin exposure on the cortical bone calcium content in ovariectomized rats.

    Science.gov (United States)

    Charoenphandhu, Narattaphol; Tudpor, Kukiat; Thongchote, Kanogwun; Saengamnart, Wasana; Puntheeranurak, Supaporn; Krishnamra, Nateetip

    2007-02-01

    High physiological prolactin induced positive calcium balance by stimulating intestinal calcium absorption, reducing renal calcium excretion, and increasing bone calcium deposition in female rats. Although prolactin-induced increase in trabecular bone calcium deposition was absent after ovariectomy, its effects on cortical bones were still controversial. The present investigation, therefore, aimed to study the effect of in vivo long-term high physiological prolactin induced by either anterior pituitary (AP) transplantation or 2.5 mg/kg prolactin injection on cortical bones in ovariectomized rats. Since the presence of prolactin receptors (PRLR) in different bones of normal adult rats has not been reported, we first determined mRNA expression of both short- and long-form PRLRs at the cortical sites (tibia and femur) and trabecular sites (calvaria and vertebrae) by using the RT-PCR. Our results showed the mRNA expression of both PRLR isoforms with predominant long form at all sites. However, high prolactin levels induced by AP transplantation in normal rats did not have any effect on the femoral bone mineral density or bone mineral content. By using (45)Ca kinetic study, 2.5 mg/kg prolactin did not alter bone formation, bone resorption, calcium deposition, and total calcium content in tibia and femur of adult ovariectomized rats. AP transplantation also had no effect on the cortical total calcium content in adult ovariectomized rats. Because previous work showed that the effects of prolactin were age dependent and could be modulated by high-calcium diet, interactions between prolactin and these two parameters were investigated. The results demonstrated that 2.0% wt/wt high-calcium diet significantly increased the tibial total calcium content in 9-wk-old young AP-grafted ovariectomized rats but decreased the tibial total calcium content in 22-wk-old adult rats. As for the vertebrae, the total calcium contents in both young and adult rats were not changed by high

  9. Rankl Impairs Lactogenic Differentiation Through Inhibition of the Prolactin/Stat5 Pathway at Midgestation.

    Science.gov (United States)

    Cordero, Alex; Pellegrini, Pasquale; Sanz-Moreno, Adrián; Trinidad, Eva M; Serra-Musach, Jordi; Deshpande, Chetan; Dougall, William C; Pujana, Miguel Angel; González-Suárez, Eva

    2016-04-01

    Prolactin and progesterone both orchestrate the proliferation and differentiation of the mammary gland during gestation. Differentiation of milk secreting alveoli depends on the presence of prolactin receptor, the downstream Jak2-Stat5 pathway and the transcription factor Elf5. A strict regulation of Rank signaling is essential for the differentiation of the mammary gland and in particular for alveolar commitment. Impaired alveologenesis and lactation failure are observed in both, knockout and Rank overexpressing mice; however, the underlying molecular mechanism responsible for these phenotypes remains largely unknown. Using genome-wide expression analyses and functional studies, we show here that Rankl (RL) exposure leads to impaired secretory differentiation of alveolar cells not only in MMTV-RANK but also in wild-type (WT) mammary acini. Conversely, pharmacological blockage of Rank signaling at midgestation in WT mice leads to precocious and exacerbated lactogenesis. Mechanistically, RL negatively regulates Stat5 phosphorylation and Elf5 expression at the onset of lactogenesis. Continuous RL exposure leads to the expansion of basal and bipotent cells in WT and MMTV-RANK acini. Overall, we demonstrate that enhanced Rank signaling impairs secretory differentiation during pregnancy by inhibition of the prolactin/p-Stat5 pathway.

  10. Prolactin and Psychopathology in Schizophrenia: A Literature Review and Reappraisal

    Directory of Open Access Journals (Sweden)

    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.

  11. Prolactin and psychopathology in schizophrenia: a literature review and reappraisal.

    Science.gov (United States)

    Rajkumar, Ravi Philip

    2014-01-01

    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.

  12. Effects of Prolactin and Lactation on A15 Dopamine Neurones in the Rostral Preoptic Area of Female Mice.

    Science.gov (United States)

    Brown, R S E; Herbison, A E; Grattan, D R

    2015-09-01

    There are several distinct populations of dopamine neurones in the hypothalamus. Some of these, such as the A12 tuberoinfundibular dopamine neurones and the A14 periventricular dopamine neurones, are known to be regulated by the anterior pituitary hormone prolactin, whereas others, such as the A13 zona incerta dopaminergic neurones, are not. The present study aimed to investigate the role of prolactin in the regulation of a fourth population of hypothalamic dopamine neurones: the A15 dopamine population in the rostral hypothalamus. These neurones may play a role in the regulation of gonadotrophin-releasing hormone (GnRH) secretion, and we hypothesised that they might contribute to the suppression of GnRH release and infertility caused by hyperprolactinaemia. Under basal (low prolactin) conditions, only 8% of A15 dopamine neurones in the anteroventral periventricular nucleus (AVPV) of vehicle-treated dioestrous mice expressed phosphorylated signal transducer and activator of transcription 5 (pSTAT5), as labelled by immunohistochemistry. We have previously shown that this transcription factor can be used as an index of prolactin-receptor activation. Following acute prolactin administration, 35% of AVPV dopamine neurones co-expressed pSTAT5, whereas, during lactation, when endogenous prolactin levels are chronically elevated, 55% of AVPV dopamine neurones expressed pSTAT5. There was also a significant increase in dopamine turnover in the rostral hypothalamus, both in the diagonal band of Broca at the level of the organum vasculosum of the lamina terminalis and in the rostral preoptic area during lactation, with the 3,4-dihydroxyphenylacetic acid/dopamine ratio increasing from 0.28 ± 0.04 and 0.14 ± 0.01 in dioestrous mice to 0.82 ± 0.06 and 0.38 ± 0.03, respectively, in day 7 lactating mice. It is not yet known whether this change is driven by the hyperprolactinaemia of lactation, or another lactation-specific signal. These data demonstrate that the A15

  13. Proliferation and mRNA expression of absorptive villous cell markers and mineral transporters in prolactin-exposed IEC-6 intestinal crypt cells.

    Science.gov (United States)

    Teerapornpuntakit, Jarinthorn; Wongdee, Kannikar; Thongbunchoo, Jirawan; Krishnamra, Nateetip; Charoenphandhu, Narattaphol

    2012-06-01

    During pregnancy and lactation, prolactin (PRL) enhances intestinal absorption of calcium and other minerals for fetal development and milk production. Although an enhanced absorptive efficiency is believed to mainly result from the upregulation of mineral transporters in the absorptive villous cells, some other possibilities, such as PRL-enhanced crypt cell proliferation and differentiation to increase the absorptive area, have never been ruled out. Here, we investigated cell proliferation and mRNA expression of mineral absorption-related genes in the PRL-exposed IEC-6 crypt cells. As expected, the cell proliferation was not altered by PRL. Inasmuch as the mRNA expressions of villous cell markers, including dipeptidylpeptidase-4, lactase and glucose transporter-5, were not increased, PRL was not likely to enhance crypt cell differentiation into the absorptive villous cells. In contrast to the previous findings in villous cells, PRL was found to downregulate the expression of calbindin-D(9k), claudin-3 and occludin in IEC-6 crypt cells, while having no effect on transient receptor potential vanilloid family channels-5/6, plasma membrane Ca(2+)-ATPase (PMCA)-1b and Na(+)/Ca(2+) exchanger-1 expression. In conclusion, IEC-6 crypt cells did not respond to PRL by increasing proliferation or differentiation into villous cells. The present results thus supported the previous hypothesis that PRL enhanced mineral absorption predominantly by increasing transporter expression and activity in the absorptive villous cells.

  14. Berberine inhibits PTP1B activity and mimics insulin action.

    Science.gov (United States)

    Chen, Chunhua; Zhang, Yuebo; Huang, Cheng

    2010-07-02

    Type 2 diabetes patients show defects in insulin signal transduction that include lack of insulin receptor, decrease in insulin stimulated receptor tyrosine kinase activity and receptor-mediated phosphorylation of insulin receptor substrates (IRSs). A small molecule that could target insulin signaling would be of significant advantage in the treatment of diabetes. Berberine (BBR) has recently been shown to lower blood glucose levels and to improve insulin resistance in db/db mice partly through the activation of AMP-activated protein kinase (AMPK) signaling and induction of phosphorylation of insulin receptor (IR). However, the underlying mechanism remains largely unknown. Here we report that BBR mimics insulin action by increasing glucose uptake ability by 3T3-L1 adipocytes and L6 myocytes in an insulin-independent manner, inhibiting phosphatase activity of protein tyrosine phosphatase 1B (PTP1B), and increasing phosphorylation of IR, IRS1 and Akt in 3T3-L1 adipocytes. In diabetic mice, BBR lowers hyperglycemia and improves impaired glucose tolerance, but does not increase insulin release and synthesis. The results suggest that BBR represents a different class of anti-hyperglycemic agents.

  15. Serum prolactin for differentiating epileptic seizures in children

    Directory of Open Access Journals (Sweden)

    Harry Mangunsong

    2015-09-01

    Full Text Available Background Serum prolactin level has been used as a marker to differentiate epileptic from non-epileptic seizures in adults. Electroencephalogram (EEG examination is the primary diagnostic tool used to assess seizures. However, EEGs are quite difficult to perform in children and have sensitivity of only 50%-55%, with 96% specificity. Objective To assess the diagnostic potential of serum prolactin level as an alternative tool for children for differentiating between epileptic and non-epileptic seizures. Methods This diagnostic study was performed between January 2013 and December 2013. Thirty patients aged 3 months to 15 years with seizures and without fever who visited the Emergency Department of Arifin Ahmad Hospital, Pekanbaru, Riau, were included. Blood specimens were collected within 2 hours after seizure. Subjects underwent serum prolactin measurements and EEG examinations. Results Fifteen subjects had normal EEGs and 15 subjects had abnormal EEGs. Post-ictal serum prolactin levels were significantly higher in the epileptiform EEG group. The mean serum prolactin levels were 23.78 (SD 21.86 ng/mL and 10.57 (SD 5.62ng/mL in patients with epileptic and non-epileptic patients, respectively. Using a prolactin cut-off point of 17.2 ng/mL, serum prolactin had a 73.3% sensitivity and 93.3% specificity for differentiating between epileptic and non-epileptic seizures. Conclusion Our findings suggest that serum prolactin level increases after an epileptic seizure, but not after a non-epileptic seizure. Post-ictal prolactin elevation within 2 hours may be useful in differentiating epileptic seizures from non-epileptic seizures.

  16. Serum prolactin for differentiating epileptic seizures in children

    Directory of Open Access Journals (Sweden)

    Harry Mangunsong

    2015-10-01

    Full Text Available Background Serum prolactin level has been used as a marker to differentiate epileptic from non-epileptic seizures in adults. Electroencephalogram (EEG examination is the primary diagnostic tool used to assess seizures. However, EEGs are quite difficult to perform in children and have sensitivity of only 50%- 55%, with 96% specificity. Objective To assess the diagnostic potential of serum prolactin level as an alternative tool for children for differentiating between epileptic and non-epileptic seizures. Methods This diagnostic study was performed between January 2013 and December 2013. Thirty patients aged 3 months to 15 years with seizures and without fever who visited the Emergency Department of Arifin Ahmad Hospital, Pekanbaru, Riau, were included. Blood specimens were collected within 2 hours after seizure. Subjects underwent serum prolactin measurements and EEG examinations. Results Fifteen subjects had normal EEGs and 15 subjects had abnormal EEGs. Post-ictal serum prolactin levels were significantly higher in the epileptiform EEG group. The mean serum prolactin levels were 23.78 (SD 21.86 ng/mL and 10.57 (SD 5.62ng/mL in patients with epileptic and non-epileptic patients, respectively. Using a prolactin cut-off point of 17.2 ng/mL, serum prolactin had a 73.3% sensitivity and 93.3% specificity for differentiating between epileptic and non-epileptic seizures. Conclusion Our findings suggest that serum prolactin level increases after an epileptic seizure, but not after a non-epileptic seizure. Post-ictal prolactin elevation within 2 hours may be useful in differentiating epileptic seizures from non-epileptic seizures.

  17. Prolactin as an autocrine/paracrine factor in breast tissue.

    Science.gov (United States)

    Clevenger, C V; Plank, T L

    1997-01-01

    The neuroendocrine hormone prolactin (PRL) stimulates breast growth and differentiation during puberty, pregnancy, and lactation. Despite extensive and convincing data indicating that PRL significantly contributes to the pathogenesis and progression of rodent mammary carcinoma, parallel observations for human breast cancer have not been concordant. In particular, the therapeutic alteration of somatolactogenic hormone levels has not consistently altered the course of human breast cancer. Recent data, however, suggest that extra-pituitary tissues are capable of elaborating PRL; indeed, the observation of sustained serum levels of PRL in post-hypophysectomy patients supports this hypothesis. Proof of an autocrine/paracrine loop for PRL within normal and malignant human breast tissues requires that the following three criteria be met: (1) PRL must be synthesized and secreted within mammary tissues; (2) the receptor for PRL (PRLR) must be present within these tissues; and, (3) proliferative responses to autocrine/paracrine PRL must be demonstrated. These criteria have now been fulfilled in several laboratories. With the demonstration of a PRL autocrine/paracrine loop in mammary glands, the basis for the ineffective treatment of human breast cancer by prior endocrine-based anti-somatolactogenic therapies is evident. These findings provide the precedent for novel therapeutic strategies aimed at interrupting the stimulation of breast cancer growth by PRL at both endocrine and autocrine/paracrine levels.

  18. Reproduction and energy balance: the integrative role of prolactin

    Directory of Open Access Journals (Sweden)

    T I Romantsova

    2014-03-01

    Full Text Available The physiological mechanisms controlling reproduction are closely linked to energy balance. In the recent years, accumulating evidence suggests that prolactin regulates metabolic functions, besides regulating breast development and stimulating milk formation. Hyperprolactinemia is associated with obesity and treatment with dopamine agonists results in weight loss. We discuss the integrated effects of prolactin in the metabolic control and reproductive function, the role of prolactin in the pathogenesis of obesity. The present review also describes the effects of treatment with cabergoline on body weight and cardiovascular risk markers.

  19. 18 CFR 1b.21 - Enforcement hotline.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Enforcement hotline. 1b..., DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.21 Enforcement hotline. (a) The Hotline Staff may provide information to the public and give informal staff opinions. The opinions...

  20. 松辽黑猪和长白猪催乳素受体基因第10外显子多态性与繁殖性状的关联分析%Association Analysis on Polymorphisms of Prolactin Receptor (PRLR) Gene Exon 10 with Reproductive Traits in Songliao Black Pig and Landrace Pig

    Institute of Scientific and Technical Information of China (English)

    刘庆雨; 于永生; 金鑫; 李娜; 李兆华; 赵晓东; 张树敏

    2012-01-01

    The purpose was to investigate the association between the polymorphisms of PRLR gene exon 10 and reproductive traits in Songliao Black pig and Landrace pig. Polymorphisms of PRLR gene exon 10 were detected by PCR-RFLP in Songliao Black pig and Landrace pig, then their genetic effects on reproductive traits were analyzed by the least square method. The results showed that there were two alleles (A and B) and three genotypes (AA, AB and BB) in the two pig species, and the frequencies of the dominant allele A were 0. 551 and 0. 578 in Songliao Black pig and Landrace pig respectively. The weaning piglets number, the number of nipples of individuals with AA genotype were significantly higher than the other two genotypes (PAB>BB trend.%试验旨在探讨催乳素受体(prolactin receptor,PRLR)基因遗传多态性及其与松辽黑猪、长白猪繁殖性状的关联性.采用PCR-RFLP方法对松辽黑猪和长白猪PRLR基因第10外显子进行了多态性检测,并运用最小二乘法分析各基因型对母猪繁殖性能的遗传效应.结果表明,两个猪种中都存在A、B 2个等位基因和AA、AB、BB 3种基因型,松辽黑猪和长白猪等位基因A的频率分别0.551和0.578,A为优势基因.两个猪种的AA基因型个体的断奶仔猪数、乳头数都显著高于其他两个基因型(P<0.05),初产松辽黑猪AA基因型个体的TNB、NBA显著高于其他基因型(P<0.05),对其他繁殖性状影响不显著,但呈现出AA>AB>BB的趋势.

  1. Prolactin protects retinal pigment epithelium by inhibiting sirtuin 2-dependent cell death.

    Science.gov (United States)

    Meléndez García, Rodrigo; Arredondo Zamarripa, David; Arnold, Edith; Ruiz-Herrera, Xarubet; Noguez Imm, Ramsés; Baeza Cruz, German; Adán, Norma; Binart, Nadine; Riesgo-Escovar, Juan; Goffin, Vincent; Ordaz, Benito; Peña-Ortega, Fernando; Martínez-Torres, Ataúlfo; Clapp, Carmen; Thebault, Stéphanie

    2016-05-01

    The identification of pathways necessary for retinal pigment epithelium (RPE) function is fundamental to uncover therapies for blindness. Prolactin (PRL) receptors are expressed in the retina, but nothing is known about the role of PRL in RPE. Using the adult RPE 19 (ARPE-19) human cell line and mouse RPE, we identified the presence of PRL receptors and demonstrated that PRL is necessary for RPE cell survival via anti-apoptotic and antioxidant actions. PRL promotes the antioxidant capacity of ARPE-19 cells by reducing glutathione. It also blocks the hydrogen peroxide-induced increase in deacetylase sirtuin 2 (SIRT2) expression, which inhibits the TRPM2-mediated intracellular Ca(2+) rise associated with reduced survival under oxidant conditions. RPE from PRL receptor-null (prlr(-/-)) mice showed increased levels of oxidative stress, Sirt2 expression and apoptosis, effects that were exacerbated in animals with advancing age. These observations identify PRL as a regulator of RPE homeostasis.

  2. Prolactin protects retinal pigment epithelium by inhibiting sirtuin 2-dependent cell death

    Directory of Open Access Journals (Sweden)

    Rodrigo Meléndez García

    2016-05-01

    Full Text Available The identification of pathways necessary for retinal pigment epithelium (RPE function is fundamental to uncover therapies for blindness. Prolactin (PRL receptors are expressed in the retina, but nothing is known about the role of PRL in RPE. Using the adult RPE 19 (ARPE-19 human cell line and mouse RPE, we identified the presence of PRL receptors and demonstrated that PRL is necessary for RPE cell survival via anti-apoptotic and antioxidant actions. PRL promotes the antioxidant capacity of ARPE-19 cells by reducing glutathione. It also blocks the hydrogen peroxide-induced increase in deacetylase sirtuin 2 (SIRT2 expression, which inhibits the TRPM2-mediated intracellular Ca2+ rise associated with reduced survival under oxidant conditions. RPE from PRL receptor-null (prlr−/− mice showed increased levels of oxidative stress, Sirt2 expression and apoptosis, effects that were exacerbated in animals with advancing age. These observations identify PRL as a regulator of RPE homeostasis.

  3. Primary Hypothyroidism With Markedly High Prolactin

    Directory of Open Access Journals (Sweden)

    MOHD SALEEM ANSARI

    2016-04-01

    Full Text Available Secondary Pituitary enlargement due to primary hypothyroidism is not a common manifestation. The loss of thyroxin feedback inhibition in primary hypothyroidism causes overproduction of thyroid-releasing hormone (TRH, which results in secondary pituitary enlargement.TRH has a weak stimulatory effect on lactotroph cells of pituitary, so mild to moderate rise in prolactin (PRL level is expected. We report a 67 years old female who presented with a large pituitary mass and very high level of TSH with a significant rise in PRL level. In this case the diagnosis of seller mass was challenging, it was difficult to distinguish between pituitary prolactinoma and primary hypothyroidism with secondary pituitary hyperplasia. The thyroid hormone replacement proved that hyperprolactinemia was due to hyperplasia of the pituitary gland.Hence, the correct diagnosis and thyroid hormone therapy can prevent unnecessary treatment with dopamine agonist.

  4. Primary Hypothyroidism with Markedly High Prolactin

    Science.gov (United States)

    Ansari, Mohd Saleem; Almalki, Mussa H.

    2016-01-01

    Secondary pituitary enlargement due to primary hypothyroidism is not a common manifestation. The loss of thyroxin feedback inhibition in primary hypothyroidism causes overproduction of thyrotropin-releasing-hormone (TRH), which results in secondary pituitary enlargement. TRH has a weak stimulatory effect on the lactotroph cells of the pituitary, so a mild to moderate increase in prolactin (PRL) levels is expected. We report the case of a 67-year-old female who presented with a large pituitary mass and a very high level of TSH in association with a significant rise in PRL level. In this case, diagnosing a sellar mass was challenging; it was difficult to distinguish between pituitary prolactinoma and primary hypothyroidism with secondary pituitary hyperplasia. Thyroid hormone replacement proved that this patient’s hyperprolactinemia was due to hyperplasia of the pituitary gland. As such, making the correct diagnosis and initiating thyroid hormone therapy can prevent unnecessary treatment with dopamine agonists. PMID:27199892

  5. Pituitary prolactin adenoma with Toxoplasma gondii infection

    Institute of Scientific and Technical Information of China (English)

    张晓晖; 李青; 程虹; 阎庆国; 黄高昇

    2003-01-01

    Objective: To report two recent cases of pituitary adenoma associated with Toxoplasma gondii (T.Gondii) infection.Methods: Histological changes were observed in H & E and PAS staining sections microscopically.Immunohistochemistry was performed to classify the pituitary tumors and to confirm the diagnosis of T.gondii.Results: The cases were 43- and 19-year-old females, in which the latter one was a recurring case, and radiology examination showed that tumors existed in sellar region.Microscopically, the tumors consisted of small homogenous polygonal or round cells with abundant eosinophilic granular cytoplasm.Immunohistochemistry revealed they were prolactin-producing adenomas.Interestingly, we found toxoplasma infection in the tumor tissues, being confirmed by T.gondii sepicific antibody immunohistochemistry.Conclusion: The association of pituitary adenoma with toxoplasma raises the possibility that T.gondii may be involved in the development of certain cases of pituitary adenoma.

  6. Effects of tibolone and its metabolites on prolactin and insulin-like growth factor binding protein-1 expression in human endometrial stromal cells.

    Science.gov (United States)

    Guzel, Elif; Buchwalder, Lynn; Basar, Murat; Kayisli, Umit; Ocak, Nehir; Bozkurt, Idil; Lockwood, Charles J; Schatz, Frederick

    2015-05-01

    The effects of the postmenopausal replacement steroid tibolone and its 3α-, 3β-OH and Δ-4 tibolone metabolites were evaluated on progesterone receptor-mediated classic decidualization markers insulin-like growth factor binding protein-1 (IGFBP-1) and prolactin expression in human endometrial stromal cells (HESCs). Supernatants of conditioned medium or erxtracted RNA from experimental cell incubations of confluent HESCs were subjected to ELISAs, Western blot analysis and RT/PCR, and results were statisically assesed. Over 21 days, specific ELISAs observed linear increases in secreted IGFBP-1 and prolactin levels elicited by tibolone and its metabolites. Cultured HESCs were refractory to E2 and dexamethasone, whereas tibolone and each metabolite exceeded medroxyprogesterone acetate in significantly elevating IGFBP-1 and prolactin output. Anti-progestins eliminated IGFBP-1 and prolactin induction by tibolone and its metabolites. Immunoblotting and RT/PCR confirmed ELISA results. These observations of IGFBP-1 and prolactin expression: (a) indicate the relevance of cultured HESCs in evaluating the chronic effects of tibolone administration to women; (b) are consistent with PR-mediated endometrial atrophy and protection against endometrial bleeding despite the persistence of circulating ER-binding, but not PR-binding metabolites following tibolone administration to women.

  7. Prolactin, psychological stress and environment in humans: adaptation and maladaptation.

    Science.gov (United States)

    Sobrinho, Luis Gonçalves

    2003-01-01

    Non-puerperal lactation and/or hyperprolactinemia in humans have been related to psychological variables in a variety of ways: (1) Non-puerperal nursing; (2) Pseudopregnancy; (3) Rapid weight gain; (4) Psychogenic galactorrhea; (5) Acute prolactin responses to psychological stress; (6) High prolactin levels in persons who cope passively in real life stress situations; (7) Paternal deprivation in women with pathological hyperprolactinemia; (8) Clinical onset of prolactinomas following life-events. Publications on the above subjects are scattered in the literature as curiosities, anecdotal case-reports or unexplained associations, as there is no theoretical frame of reference to accommodate them. We propose that prolactin is a component of a biological, "maternal", subroutine, adaptive to the care of the young, which promotes accumulation of fat for the extraordinary expenses of pregnancy and lactation, the production of milk and maternal behavior. In an attempt to characterize the stimuli responsible for the activation of the maternal subroutine in the absence of pregnancy we studied the hormonal profiles of female volunteers during three types of sessions under hypnosis: (1) Relaxation-only, control sessions; (2) Sessions in which a fantasy of "nursing" was induced; (3) Sessions of evocations of memories. Prolactin surges were related to the evocation, with rage, of humiliating experiences, but not with the fantasy of nursing. Cortisol surges were related to surprise and shock and were negatively associated with prolactin. In conclusion--Prolactin and cortisol are measurable markers of two different, and alternative, coping strategies to "psychological stress".

  8. Mammary gland copper transport is stimulated by prolactin through alterations in Ctr1 and Atp7A localization.

    Science.gov (United States)

    Kelleher, Shannon L; Lönnerdal, Bo

    2006-10-01

    Milk copper (Cu) concentration declines and directly reflects the stage of lactation. Three Cu-specific transporters (Ctr1, Atp7A, Atp7B) have been identified in the mammary gland; however, the integrated role they play in milk Cu secretion is not understood. Whereas the regulation of milk composition by the lactogenic hormone prolactin (PRL) has been documented, the specific contribution of PRL to this process is largely unknown. Using the lactating rat as a model, we determined that the normal decline in milk Cu concentration parallels declining Cu availability to the mammary gland and is associated with decreased Atp7B protein levels. Mammary gland Cu transport was highest during early lactation and was stimulated by suckling and hyperprolactinemia, which was associated with Ctr1 and Atp7A localization at the plasma membrane. Using cultured mammary epithelial cells (HC11), we demonstrated that Ctr1 stains in association with intracellular vesicles that partially colocalize with transferrin receptor (recycling endosome marker). Atp7A was primarily colocalized with mannose 6-phosphate receptor (M6PR; late endosome marker), whereas Atp7B was partially colocalized with protein disulfide isomerase (endoplasmic reticulum marker), TGN38 (trans-Golgi network marker) and M6PR. Prolactin stimulated Cu transport as a result of increased Ctr1 and Atp7A abundance at the plasma membrane. Although the molecular mechanisms responsible for these posttranslational changes are not understood, transient changes in prolactin signaling play a role in the regulation of mammary gland Cu secretion during lactation.

  9. Construction of HEK293 cells stably expressing wild-type organic anion transporting polypeptide 1B1 (OATP1B1*1a) and variant OATP1B1*1b and OATP1B1*15.

    Science.gov (United States)

    Chen, M; Qu, B X; Chen, X L; Hu, H H; Jiang, H D; Yu, L S; Zhou, Q; Zeng, S

    2016-06-01

    A transgenic cell line stably expressing the human organic anion transporting polypeptide (OATP1B1) was established. Human Embryonic Kidney 293 (HEK293) cell line stably expressing OATP1B1*1a sequence was amplified through PCR with the extracted total RNA as templates from human liver, then subcloned into the plasmid pMD19-T and verified by sequencing. OATP1B1*1b/OATP1B1*15 mutant sequences were obtained by site-directed mutation PCR with pMD19-T/ OATP1B1*1a as templates. The plasmids pcDNA3.1(+)/OATP1B1*1a, *1b and *15 were constructed and transfected into HEK293 cell line using Lipofectamine 2000 transfection reagent. Several stable transfected clones were obtained after selection with G418. Using rosuvastatin as a probe substrate of OATP1B1, the intracellular rosuvastatin accumulation in HEK293 and HEK-OATP1B1*1a, *1b and *15 monoclone cells were validated by a ultra-performance liquid chromatography-tandem mass spectrometry. OATP1B1 mRNA and protein expression were detected by RT-PCR and Western blot, respectively. The results from RT-PCR, rosuvastatin uptake and Western blot assay indicated that human OATP1B1 was highly expressed in transfected cells compared with controls. The HEK-293 cell lines stably expressing human OATP1B1-wild and variant (HEK-OATP1B1, *1b and *15) are potential models to study drug transport in vitro.

  10. Discovery of a novel competitive inhibitor of PTP1B by high-throughput screening

    Institute of Scientific and Technical Information of China (English)

    Lei SHI; Hai-ping YU; Yue-yang ZHOU; Jun-qin DU; Qiang SHEN; Jing-ya LI; Jia LI

    2008-01-01

    Aim: The aim of the present study was to discover novel protein tyrosine phos-phatase 1B (PTP1B) inhibitors. We expressed and purified the human PTP1B catalytic domain and set up a molecular level high-throughput screening (HTS) assay to screen a set of 48 000 pure compounds. Results: HTS was finished with an averaged Z' factor of 0.63, and LGH00081, a competitive inhibitor of PTP1B with novel structure and relatively good selectivity for receptor-type protein ty-rosine phosphatases, was identified. Conclusion: We established a molecular level assay which is useful for the screening of PTP1B inhibitors with therapeutic potential. The novel competitive PTP1B inhibitor LGH00081 offers a good start for structure modification and cellular functional activity study.

  11. Immunological properties of prolactin and studies on a gonadotropin binding inhibitor

    Energy Technology Data Exchange (ETDEWEB)

    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/sup 125/I, a very sensitive (0.4-0.6 ng/ml) and highly specific homologous RIA for ePRL was developed. A heterologous RIA using /sup 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 /sup 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.

  12. Serum prolactin concentrations are elevated after syncope.

    Science.gov (United States)

    Oribe, E; Amini, R; Nissenbaum, E; Boal, B

    1996-07-01

    The distinction between syncope and epileptic seizures is a common clinical diagnostic problem. Elevated serum prolactin (PRL) concentrations are used to help differentiate epileptic from nonepileptic attacks such as pseudoseizures. Reports of PRL concentrations following syncope have been variable. To determine whether PRL rises after syncope, we measured serum PRL concentrations during a 45-minute passive 60-degree head-up tilt in 21 patients with a history of near-fainting or syncope. Head-up tilt triggered hypotension (mean arterial pressure 51 mm Hg, 95% CI = 45-57) with syncope in 11 patients. PRL concentrations were elevated ( > 19 ng/mL) and reached a maximum within the first 30 minutes after tilt-induced syncope in nine patients (PRL supine: 11 ng/mL, 95% CI = 7-15, vs. PRL after syncope: 52 ng/mL, 95% CI = 36-67; a greater than fourfold rise), while they remained unchanged in 10 patients who had a normal response to head-up tilt (PRL supine: 6 ng/mL, 95% CI = 5-8, vs. maximum PRL while upright: 8 ng/mL, 95% CI = 6-10). The findings indicate that elevated PRL concentrations are present after hypotensive syncope and are of little use in differentiating such syncope from epileptic seizures.

  13. Serum prolactin levels and sexual dysfunctions in antipsychotic medication, such as risperidone : a review

    NARCIS (Netherlands)

    Knegtering, H; Lambers, PA; Prakken, G; ten Brink, C

    2000-01-01

    Classical antipsychotic drugs increase the level of serum prolactin. The atypical antipsychotic clozapine barely increases prolactin levels. An open naturalistic study in the University Hospital of Groningen suggests that treatment with risperidone in comparison to classical antipsychotics seems to

  14. RELATIONSHIP BETWEEN PROLACTIN HORMONE LEVEL, MOLTING AND DUCK EGG PRODUCTION

    Directory of Open Access Journals (Sweden)

    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.

  15. Prolactin gene expression in primary central nervous system tumors

    Directory of Open Access Journals (Sweden)

    Mendes Graziella Alebrant

    2013-01-01

    Full Text Available Abstract Background Prolactin (PRL is a hormone synthesized in both the pituitary gland and extrapituitary sites. It has been associated with the occurrence of neoplasms and, more recently, with central nervous system (CNS neoplasms. The aim of this study was to evaluate prolactin expression in primary central nervous system tumors through quantitative real-time PCR and immunohistochemistry (IH. Results Patient mean age was 49.1 years (SD 15.43, and females accounted for 70% of the sample. The most frequent subtype of histological tumor was meningioma (61.5%, followed by glioblastoma (22.9%. Twenty cases (28.6% showed prolactin expression by immunohistochemistry, most of them females (18 cases, 90%. Quantitative real-time PCR did not show any prolactin expression. Conclusions Despite the presence of prolactin expression by IH, the lack of its expression by quantitative real-time PCR indicates that its presence in primary tumors in CNS is not a reflex of local production.

  16. 2000 Johnston Site 1B-P

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Underwater Site 1B-P was established at Johnston Atoll by Dr. James Maragos, U.S. Fish & Wildlife Service, on June 29, 2000. With a start point (meter 0) at...

  17. Recombinant Human Prolactin Protects against Irradiation Induced Myelosuppression

    Institute of Scientific and Technical Information of China (English)

    Weici Zhang; Rui Sun; Jianhua Zhang; Jian Zhang; Zhigang Tian

    2005-01-01

    Prolactin is a multifunctional hormone that exerts many separate functions and acts as an important connection between the endocrine and immune systems. There are increasing researches implicating the role of prolactin in hematopoiesis. Enhanced erythropoiesis in pregnant women and direct erythropoietic effects in vitro of plasma either from pregnant or lactating mice have been reported. Furthermore, regression of erythroblastic leukemia has been observed in a significant number of rats after hypophysectomy. In this study, the effects of recombinant human prolactin (rhPRL) on hematopoiesis were assessed in irradiated mice. Mice were treated with rhPRL for five consecutive days after exposure to a lethal dose or a sub-dose irradiation. Prolonged survival rate and increased erythropoiesis were observed in the irradiation-induced myelosuppressive mice. It was concluded that rhPRL might act on erythropoiesis and could be a potential candidate for the treatment of irradiation-induced myelosuppresion in clinic. Cellular & Molecular Immunology.

  18. Tobacco smoke induces CYP1B1 in the aerodigestive tract.

    Science.gov (United States)

    Port, Jeffrey L; Yamaguchi, Kentaro; Du, Baoheng; De Lorenzo, Mariana; Chang, Mindy; Heerdt, Paul M; Kopelovich, Levy; Marcus, Craig B; Altorki, Nasser K; Subbaramaiah, Kotha; Dannenberg, Andrew J

    2004-11-01

    Several members of the P450 family, including cytochrome P450 1B1 (CYP1B1), can convert tobacco smoke (TS) procarcinogens, including benzo[a]pyrene (B[a]P), to carcinogenic intermediates. In this study we investigated the effects of TS condensate and B[a]P on the expression of CYP1B1 in vitro and in vivo. CYP1B1 mRNA and protein were induced by both TS condensate and B[a]P in cell lines derived from the human aerodigestive tract. Treatment with TS condensate stimulated binding of the aryl hydrocarbon receptor (AhR) to an oligonucleotide containing a canonical xenobiotic response element (XRE) site and induced XRE-luciferase activity. These findings are consistent with prior evidence that polycyclic aromatic hydrocarbons, known ligands of the AhR, stimulate CYP1B1 transcription by an XRE-dependent mechanism. To determine whether these in vitro findings applied in vivo, both murine and human studies were carried out. Short-term exposure to TS induced CYP1B1 in the tongue, esophagus, lung and colon of experimental mice. In contrast, CYP1B1 was not induced by TS in the aorta of these mice. Levels of CYP1B1 mRNA were also elevated in the bronchial mucosa of human tobacco smokers versus never smokers (P CYP1B1 in TS-induced carcinogenesis in the aerodigestive tract.

  19. Hypotensive action of prolactin in rats with spontaneous hypertension.

    Science.gov (United States)

    Ryszka, F; Ludyga, K; Strokowska, M; Krupej, J; Gaus, I; Zych, F

    1984-01-01

    Rats (SHR) weighing 240 +/- 10 g with spontaneous hypertension were given intraperitoneally porcine prolactin in doses from 0.2 to 2000 micrograms/kg of body weight. The systolic pressure was measured before hormone administration and 2 hours after it. It was found that prolactin in doses of 200 to 2000 micrograms/kg caused a decrease of the systolic pressure by 22%. The dose of 20 micrograms/kg decreased this pressure by 9% and the dose of 0.2 microgram/kg by 7.9%.

  20. Mechanism of protein tyrosine phosphatase 1B-mediated inhibition of leptin signalling

    DEFF Research Database (Denmark)

    Lund, I K; Hansen, J A; Andersen, H S

    2005-01-01

    Upon leptin binding, the leptin receptor is activated, leading to stimulation of the JAK/STAT signal transduction cascade. The transient character of the tyrosine phosphorylation of JAK2 and STAT3 suggests the involvement of protein tyrosine phosphatases (PTPs) as negative regulators...... of this signalling pathway. Specifically, recent evidence has suggested that PTP1B might be a key regulator of leptin signalling, based on the resistance to diet-induced obesity and increased leptin signalling observed in PTP1B-deficient mice. The present study was undertaken to investigate the mechanism by which...... PTP1B mediates the cessation of the leptin signal transduction. Leptin-induced activation of a STAT3 responsive reporter was dose-dependently inhibited by co-transfection with PTP1B. No inhibition was observed when a catalytically inactive mutant of PTP1B was used or when other PTPs were co...

  1. Inhibition of protein tyrosine phosphatase 1B by lignans from Myristica fragrans.

    Science.gov (United States)

    Yang, Senugmi; Na, Min Kyun; Jang, Jun Pil; Kim, Kyung Ah; Kim, Bo Yeon; Sung, Nak Ju; Oh, Won Keun; Ahn, Jong Seog

    2006-08-01

    Inhibition of protein tyrosine phosphatase 1B (PTP1B) has been proposed as one of the drug targets for treating type 2 diabetes and obesity. Bioassay-guided fractionation of a MeOH extract of the semen of Myristica fragrans Houtt. (Myristicaceae) afforded PTP1B inhibitory compounds, meso-dihydroguaiaretic acid (1) and otobaphenol (2). Compounds 1 and 2 inhibited PTP1B with IC(50) values of 19.6 +/- 0.3 and 48.9 +/- 0.5 microM, respectively, in the manner of non-competitive inhibitors. Treatment with compound 1 on 32D cells overexpressing the insulin receptor (IR) resulted in a dose-dependent increase in the tyrosine phosphorylation of IR. These results indicate that compound 1 can act as an enhancing agent in intracellular insulin signaling, possibly through the inhibition of PTP1B activity.

  2. Interactions of histaminergic and serotonergic neurons in the hypothalamic regulation of prolactin and ACTH secretion.

    Science.gov (United States)

    Jørgensen, H; Knigge, U; Kjaer, A; Warberg, J

    1996-11-01

    Serotonergic and histaminergic neuronal systems are both involved in mediation of the stress-induced release of the pituitary hormones prolactin (PRL) and ACTH. We investigated the possibility of an interaction between serotonin (5-HT) and histamine (HA) in regulation of PRL and ACTH secretion in conscious male rats. Animals were pretreated systemically with antagonists to 5-HT1, 5-HT2 or 5-HT3 receptors prior to intracerebroventricular (icv) administration of HA. The 5-HT1 + 2 receptor antagonist methysergide prevented and the 5-HT2 receptor antagonist LY 53857 attenuated the HA-induced PRL release while the 5-HT3 receptor antagonist ondansetron had no effect on this response. None of the three 5-HT receptor antagonists affected the ACTH response to HA. Specific blockade of HA synthesis by alpha-fluoromethylhistidine or blockade of postsynaptic HA receptors by icv infusion of the H1 receptor antagonist mepyramine or the H2 receptor antagonist cimetidine inhibited the PRL response to 5-HT or to the 5-HT precursor 5-hydroxytryptophan (5- HTP) given in combination with the 5-HT reuptake inhibitor fluoxetine (Flx). Blockade of the histaminergic system had no effect on the ACTH response to serotonergic stimulation. The H3 receptors are inhibitory HA receptors. Systemic pretreatment with the H3 receptor agonist R(alpha)methylhistamine, or the H3 receptor antagonist thioperamide had no effect on the hormone response to activation of the serotonergic system by 5-HTP plus Flx. We conclude that the serotonergic and histaminergic neuronal systems interact in their stimulation of PRL secretion, but not in their stimulation of ACTH secretion. This interaction involves serotonergic 5-HT1 and 5-HT2 receptors and histaminergic H1 and H2 receptors. Furthermore, the previously observed inhibitory effect of the H3 receptor agonist R(alpha)methylhistamine on stress-induced PRL and ACTH release seems not to be exerted by activation of presynaptic H3 receptors located on serotonergic

  3. Is prolactin the missing link in adipose tissue dysfunction of polycystic ovary syndrome patients?

    Science.gov (United States)

    Albu, Alice; Florea, Suzana; Fica, Simona

    2016-01-01

    The aims of the study were to evaluate whether adiposity was among the determinants of circulating prolactin levels and to determine whether serum prolactin independently predicted metabolic abnormalities in patients with polycystic ovary syndrome (PCOS). A total of 322 PCOS patients with normal serum prolactin levels were recruited between January 2007 and January 2014. Anthropometric, metabolic, and hormonal parameters were measured in all of the patients. HOMA-IR was calculated as an index of insulin resistance. Serum prolactin was negatively correlated with age (p prolactin after adjustment for age, leptin, and anthropometrical adiposity parameters. Of the adiposity parameters, only WHR and VAI were independent predictors of serum prolactin after adjustment for adiponectin. Circulating prolactin was also negatively correlated with fasting glycemia (only in patients with normal glucose metabolism, p = 0.037) and was inversely correlated with the presence of metabolic syndrome (p prolactin level was related to adipose tissue quantity and function, and adiponectin was a possible mediator of this relationship. Low serum prolactin levels were associated with an unfavorable metabolic profile, but this association seemed to be due to the complex interplay among prolactin, adiposity, and insulin resistance rather than to a direct metabolic effect of prolactin.

  4. Chlorpromazine, haloperidol, metoclopramide and domperidone release prolactin through dopamine antagonism at low concentrations but paradoxically inhibit prolactin release at high concentrations.

    Science.gov (United States)

    Besser, G. M.; Delitala, G.; Grossman, A.; Stubbs, W. A.; Yeo, T.

    1980-01-01

    1. The effects of chlorpromazine, haloperidol, metoclopramide and domperidone on the release of prolactin from perfused columns of dispersed rat anterior pituitary cells were studied. 2. Chlorpromazine, haloperidol, metoclopramide and domperidone antagonized the dopamine-mediated inhibition of prolactin release at low concentrations. 3. Each dopamine antagonist displaced the dose-response curve for dopamine-induced suppression of prolactin release to the right in a parallel manner. 4. At higher concentrations, the four drugs became less effective as dopamine antagonists. 5. At high concentrations in the absence of dopamine, chlorpromazine, haloperidol, metoclopramide and domperidone paradoxically suppressed prolactin secretion by an unknown mechanism. PMID:6110459

  5. Glucose administration does not modulate prolactin response to exercise, TRH or haloperidol injection.

    Science.gov (United States)

    Vigas, M; Jezová, D

    1994-01-01

    Glucose was found to exert an In vitro regulatory effect on prolactin secretion. Its role in the modulation of stimulated secretion of prolactin in man is, however, not clear. To evaluate the effect of hyperglycaemia on prolactin release, three stimulatory tests with different mechanisms of stimulation were employed. Healthy male subjects served as volunteers during submaximal exercise, TRH test (0.2 mg i.v.) and administration of haloperidol (2 mg i.v.). Glucose (100 g in 400 ml) or an equal volume of water was given 30 min before the tests. Blood for glucose and prolactin analysis was taken via an indwelling catheter. The plasma prolactin concentration increased in response to each of the stimuli applied. However, the prolactin increase during hyperglycaemia did not differ from values obtained in tests performed in normoglycaemia after water administration. These results indicate that prolactin release in healthy man is not modulated by hyperglycaemia.

  6. Human prolactin - 24-hour pattern with increased release during sleep.

    Science.gov (United States)

    Sassin, J. F.; Weitzman, E. D.; Kapen, S.; Frantz, A. G.

    1972-01-01

    Human prolactin was measured in plasma by radioimmunoassay at 20-minute intervals for a 24-hour period in each of six normal adults, whose sleep-wake cycles were monitored polygraphically. A marked diurnal variation in plasma concentrations was demonstrated, with highest values during sleep. Periods of episodic release occurred throughout the 24 hours.

  7. Neural regulation and dynamics of prolactin secretion in the rat.

    NARCIS (Netherlands)

    Wiersma, J.

    1990-01-01

    The subject of this thesis was an investigation of the neural regulation and dynamics of prolactin (Prl) secretion. Experimentation was performed with freely behaving undisturbed male and female rats, chronically fitted with an atrial blood sampling catheter. In some studies rats were also equip

  8. DOPAMINE AND TRH-INDUCED PROLACTIN SECRETION IN PSEUDOPREGNANT RATS

    NARCIS (Netherlands)

    SCHUILING, GA; VALKHOF, N; MOES, H; KOITER, TR

    1993-01-01

    The stimulatory effect of TRH on prolactin (Prl) secretion by the anterior pituitary gland (APG) of the pseudopregnant (PSP) rat was studied in vivo and in vitro. TRH, 500 mug, did not increase Prl release during the Prl peaks which are generated daily between 01.00 and 12.00 for about 10 days (mean

  9. Expression of functional growth hormone receptor in a mouse L cell line infected with recombinant vaccinia virus

    NARCIS (Netherlands)

    Strous, G J; van Kerkhof, P; Verheijen, C; Rossen, J W; Liou, W; Slot, J W; Roelen, C A; Schwartz, A L

    1994-01-01

    The growth hormone receptor is a member of a large family of receptors including the receptors for prolactin and interleukins. Upon binding to one molecule of growth hormone two growth hormone receptor polypeptides dimerize. We have expressed the rabbit growth hormone receptor DNA in transfected mou

  10. Reevaluation of the proposed autocrine proliferative function of prolactin in breast cancer

    DEFF Research Database (Denmark)

    Nitze, Louise Maymann; Galsgaard, Elisabeth Douglas; Din, Nanni

    2013-01-01

    synthesised PRL in breast cancer. We analysed the expression of PRL in human breast cancer tumours using qPCR analysis and in situ hybridization (ISH). PRL mRNA expression was very low or undetectable in the majority of samples in three cDNA arrays representing samples from 144 breast cancer patients...... and in 13 of 14 breast cancer cell lines when analysed by qPCR. In accordance, PRL expression did not reach detectable levels in any of the 19 human breast carcinomas or 5 cell lines, which were analysed using a validated ISH protocol. Two T47D-derived breast cancer cell lines were stably transfected......The pituitary hormone prolactin (PRL) has been implicated in tumourigenesis. Expression of PRL and its receptor (PRLR) was reported in human breast epithelium and breast cancer cells. It was suggested that PRL may act as an autocrine/paracrine growth factor. Here, we addressed the role of locally...

  11. Myelin protein zero gene mutated in Charcot-Marie-Tooth type 1B patients

    Energy Technology Data Exchange (ETDEWEB)

    Su, Ying; Li, Lanying; Lepercq, J.; Lebo, R.V. (Univ. of California, San Francisco, CA (United States)); Brooks, D.G.; Ravetch, J.V. (Sloan-Kettering Institute, New York, NY (United States)); Trofatter, J.A. (Massachusetts General Hospital, Boston, MA (United States))

    1993-11-15

    The autosomal dominant of Charcot-Marie-Tooth disease (CMT), whose gene is type 1B (CMT1B), has slow nerve conduction with demyelinated Schwann cells. In this study the abundant peripheral myelin protein zero (MPZ) gene, MPZ, was mapped 130 kb centromeric to the Fc receptor immunoglobulin gene cluster in band 1q22, and a major MPZ point mutation was found to cosegregate with CMT1B in one large CMT1B family. The MPZ point mutation in 18 of 18 related CMT1B pedigree 1 patients converts a positively charged lysine in codon 96 to a negatively charged glutamate. The same MPZ locus cosegregates with the CMT1B disease gene in a second CMT1B family [total multipoint logarithm of odds (lod) = 11.4 at [theta] = 0.00] with a splice junction mutation. Both mutations occur in MPZ protein regions otherwise conserved identically in human, rat, and cow since these species diverged 100 million years ago. MPZ protein, expressed exclusively in myelinated peripheral nerve Schwann cells, constitutes >50% of myelin protein. These mutations are anticipated to disrupt homophilic MPZ binding and result in CMT1B peripheral nerve demyelination.

  12. PTP1B inhibition suggests a therapeutic strategy for Rett syndrome.

    Science.gov (United States)

    Krishnan, Navasona; Krishnan, Keerthi; Connors, Christopher R; Choy, Meng S; Page, Rebecca; Peti, Wolfgang; Van Aelst, Linda; Shea, Stephen D; Tonks, Nicholas K

    2015-08-01

    The X-linked neurological disorder Rett syndrome (RTT) presents with autistic features and is caused primarily by mutations in a transcriptional regulator, methyl CpG-binding protein 2 (MECP2). Current treatment options for RTT are limited to alleviating some neurological symptoms; hence, more effective therapeutic strategies are needed. We identified the protein tyrosine phosphatase PTP1B as a therapeutic candidate for treatment of RTT. We demonstrated that the PTPN1 gene, which encodes PTP1B, was a target of MECP2 and that disruption of MECP2 function was associated with increased levels of PTP1B in RTT models. Pharmacological inhibition of PTP1B ameliorated the effects of MECP2 disruption in mouse models of RTT, including improved survival in young male (Mecp2-/y) mice and improved behavior in female heterozygous (Mecp2-/+) mice. We demonstrated that PTP1B was a negative regulator of tyrosine phosphorylation of the tyrosine kinase TRKB, the receptor for brain-derived neurotrophic factor (BDNF). Therefore, the elevated PTP1B that accompanies disruption of MECP2 function in RTT represents a barrier to BDNF signaling. Inhibition of PTP1B led to increased tyrosine phosphorylation of TRKB in the brain, which would augment BDNF signaling. This study presents PTP1B as a mechanism-based therapeutic target for RTT, validating a unique strategy for treating the disease by modifying signal transduction pathways with small-molecule drugs.

  13. 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.

  14. Prolactin and cortisol levels in women with endometriosis.

    Science.gov (United States)

    Lima, A P; Moura, M D; Rosa e Silva, A A M

    2006-08-01

    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.

  15. Regulation of brown fat adipogenesis by protein tyrosine phosphatase 1B.

    Directory of Open Access Journals (Sweden)

    Kosuke Matsuo

    Full Text Available Protein-tyrosine phosphatase 1B (PTP1B is a physiological regulator of insulin signaling and energy balance, but its role in brown fat adipogenesis requires additional investigation.To precisely determine the role of PTP1B in adipogenesis, we established preadipocyte cell lines from wild type and PTP1B knockout (KO mice. In addition, we reconstituted KO cells with wild type, substrate-trapping (D/A and sumoylation-resistant (K/R PTP1B mutants, then characterized differentiation and signaling in these cells. KO, D/A- and WT-reconstituted cells fully differentiated into mature adipocytes with KO and D/A cells exhibiting a trend for enhanced differentiation. In contrast, K/R cells exhibited marked attenuation in differentiation and lipid accumulation compared with WT cells. Expression of adipogenic markers PPARγ, C/EBPα, C/EBPδ, and PGC1α mirrored the differentiation pattern. In addition, the differentiation deficit in K/R cells could be reversed completely by the PPARγ activator troglitazone. PTP1B deficiency enhanced insulin receptor (IR and insulin receptor substrate 1 (IRS1 tyrosyl phosphorylation, while K/R cells exhibited attenuated insulin-induced IR and IRS1 phosphorylation and glucose uptake compared with WT cells. In addition, substrate-trapping studies revealed that IRS1 is a substrate for PTP1B in brown adipocytes. Moreover, KO, D/A and K/R cells exhibited elevated AMPK and ACC phosphorylation compared with WT cells.These data indicate that PTP1B is a modulator of brown fat adipogenesis and suggest that adipocyte differentiation requires regulated expression of PTP1B.

  16. 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.)

  17. 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 prolactin among premenopausal women, but inversely among postmenopausal. Age was related to prolactin among postmenopausal women only. Our study indicates that rotating 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.

  18. Effects of bromocriptine on serum prolactin levels, pituitary weight and immunoreactive prolactin cells in estradiol-treated ovariectomized rats: an experimental model of estrogen-dependent hyperprolactinemia

    Directory of Open Access Journals (Sweden)

    M.F. Ribeiro

    1997-01-01

    Full Text Available The present study was designed to assess the effects of bromocriptine, a dopamine agonist, on pituitary wet weight, number of immunoreactive prolactin cells and serum prolactin concentrations in estradiol-treated rats. Ovariectomized Wistar rats were injected subcutaneously with sunflower oil vehicle or estradiol valerate (50 or 300 µg rat-1 week-1 for 2, 4 or 10 weeks. Bromocriptine (0.2 or 0.6 mg rat-1 day-1 was injected daily during the last 5 or 12 days of estrogen treatment. Data were compared with those obtained for intact control rats. Administration of both doses of estrogen increased serum prolactin levels. No difference in the number of prolactin cells in rats treated with 50 µg estradiol valerate was observed compared to intact adult animals. In contrast, rats treated with 300 µg estradiol valerate showed a significant increase in the number of prolactin cells (P<0.05. Therefore, the increase in serum prolactin levels observed in rats treated with 50 µg estradiol valerate, in the absence of morphological changes in the pituitary cells, suggests a "functional" estrogen-induced hyperprolactinemia. Bromocriptine decreased prolactin levels in all estrogen-treated rats. The administration of this drug to rats previously treated with 300 µg estradiol valerate also resulted in a significant decrease in pituitary weight and number of prolactin cells when compared to the group treated with estradiol alone. The general antiprolactinemic and antiproliferative pituitary effects of bromocriptine treatment reported here validate the experimental model of estrogen-induced hyperprolactinemic rats

  19. GIFTS SM EDU Level 1B algorithms

    Science.gov (United States)

    Tian, Jialin; Gazarik, Michael J.; Reisse, Robert A.; Johnson, David G.

    2007-10-01

    The Geosynchronous Imaging Fourier Transform Spectrometer (GIFTS) Sensor Module (SM) Engineering Demonstration Unit (EDU) is a high resolution spectral imager designed to measure infrared (IR) radiances using a Fourier transform spectrometer (FTS). The GIFTS instrument employs three focal plane arrays (FPAs), which gather measurements across the long-wave IR (LWIR), short/mid-wave IR (SMWIR), and visible spectral bands. The raw interferogram measurements are radiometrically and spectrally calibrated to produce radiance spectra, which are further processed to obtain atmospheric profiles via retrieval algorithms. This paper describes the GIFTS SM EDU Level 1B algorithms involved in the calibration. The GIFTS Level 1B calibration procedures can be subdivided into four blocks. In the first block, the measured raw interferograms are first corrected for the detector nonlinearity distortion, followed by the complex filtering and decimation procedure. In the second block, a phase correction algorithm is applied to the filtered and decimated complex interferograms. The resulting imaginary part of the spectrum contains only the noise component of the uncorrected spectrum. Additional random noise reduction can be accomplished by applying a spectral smoothing routine to the phase-corrected spectrum. The phase correction and spectral smoothing operations are performed on a set of interferogram scans for both ambient and hot blackbody references. To continue with the calibration, we compute the spectral responsivity based on the previous results, from which, the calibrated ambient blackbody (ABB), hot blackbody (HBB), and scene spectra can be obtained. We now can estimate the noise equivalent spectral radiance (NESR) from the calibrated ABB and HBB spectra. The correction schemes that compensate for the fore-optics offsets and off-axis effects are also implemented. In the third block, we developed an efficient method of generating pixel performance assessments. In addition, a

  20. GIFTS SM EDU Level 1B Algorithms

    Science.gov (United States)

    Tian, Jialin; Gazarik, Michael J.; Reisse, Robert A.; Johnson, David G.

    2007-01-01

    The Geosynchronous Imaging Fourier Transform Spectrometer (GIFTS) SensorModule (SM) Engineering Demonstration Unit (EDU) is a high resolution spectral imager designed to measure infrared (IR) radiances using a Fourier transform spectrometer (FTS). The GIFTS instrument employs three focal plane arrays (FPAs), which gather measurements across the long-wave IR (LWIR), short/mid-wave IR (SMWIR), and visible spectral bands. The raw interferogram measurements are radiometrically and spectrally calibrated to produce radiance spectra, which are further processed to obtain atmospheric profiles via retrieval algorithms. This paper describes the GIFTS SM EDU Level 1B algorithms involved in the calibration. The GIFTS Level 1B calibration procedures can be subdivided into four blocks. In the first block, the measured raw interferograms are first corrected for the detector nonlinearity distortion, followed by the complex filtering and decimation procedure. In the second block, a phase correction algorithm is applied to the filtered and decimated complex interferograms. The resulting imaginary part of the spectrum contains only the noise component of the uncorrected spectrum. Additional random noise reduction can be accomplished by applying a spectral smoothing routine to the phase-corrected spectrum. The phase correction and spectral smoothing operations are performed on a set of interferogram scans for both ambient and hot blackbody references. To continue with the calibration, we compute the spectral responsivity based on the previous results, from which, the calibrated ambient blackbody (ABB), hot blackbody (HBB), and scene spectra can be obtained. We now can estimate the noise equivalent spectral radiance (NESR) from the calibrated ABB and HBB spectra. The correction schemes that compensate for the fore-optics offsets and off-axis effects are also implemented. In the third block, we developed an efficient method of generating pixel performance assessments. In addition, a

  1. Identifying and structurally characterizing CD1b in Aotus nancymaae owl monkeys.

    Science.gov (United States)

    Castillo, Fabio; Guerrero, Carlos; Trujillo, Esperanza; Delgado, Gabriela; Martinez, Pilar; Salazar, Luz M; Barato, Paola; Patarroyo, Manuel E; Parra-López, Carlos

    2004-10-01

    This study reports the molecular characterization and tissue expression of the non-human Aotus nancymaae primate CD1b isoform in the search for an experimental animal model to be used in evaluating the role of non-peptide antigen-presentation molecules in the immune response to infectious agents. CD1b expression on the surface of A. nancymaae peripheral blood monocyte-derived dendritic cells, shown by flow cytometry, was made possible by using human CD1b isoform antibodies. Studying the expression of CD1b-encoded transcripts revealed this molecule's broad distribution in several tissues. The A. nancymaae CD1b transcript-encoded amino-acid sequence showed 95.5% identity with the human sequence. Such high sequence homology was reflected in the identical structural conservation of how pockets A', C' and F' and tunnel T' conforming the antigen's binding site are organized, the similar arrangement of those amino-acids interacting with the T-cell receptor (TCR) during antigen presentation, and the conservation of YQNI-motif sequence in the cytoplasmatic tail (responsible for the molecule's intracellular trafficking in humans). Comparing the structure of human CD1a and CD1b and mouse CD1d proteins with CD1b structure in A. nancymaae obtained by minimization revealed that changes in the latter molecule's alpha1 and alpha2 domains imposed a narrowing of the antigen-binding groove in A. nancymaae CD1b. The high structural similarity between A. nancymaae CD1b and that from humans presented in this study leads to A. nancymaae being proposed as a suitable experimental animal model for analyzing CD1b in vivo, mainly in bacterial and parasite infections such as tuberculosis and malaria, respectively.

  2. Prolactin regulates transcription of the ion uptake Na+/Cl- cotransporter (ncc) gene in zebrafish gill

    Science.gov (United States)

    Breves, Jason P.; Serizier, Sandy B.; Goffin, Vincent; McCormick, Stephen D.; Karlstrom, Rolf O.

    2013-01-01

    Prolactin (PRL) is a well-known regulator of ion and water transport within osmoregulatory tissues across vertebrate species, yet how PRL acts on some of its target tissues remains poorly understood. Using zebrafish as a model, we show that ionocytes in the gill directly respond to systemic PRL to regulate mechanisms of ion uptake. Ion-poor conditions led to increases in the expression of PRL receptor (prlra), Na+/Cl− cotransporter (ncc; slc12a10.2), Na+/H+ exchanger (nhe3b; slc9a3.2), and epithelial Ca2+ channel (ecac; trpv6) transcripts within the gill. Intraperitoneal injection of ovine PRL (oPRL) increased ncc and prlra transcripts, but did not affect nhe3b or ecac. Consistent with direct PRL action in the gill, addition of oPRL to cultured gill filaments stimulated ncc in a concentration-dependent manner, an effect blocked by a pure human PRL receptor antagonist (Δ1-9-G129R-hPRL). These results suggest that PRL signaling through PRL receptors in the gill regulates the expression of ncc, thereby linking this pituitary hormone with an effector of Cl− uptake in zebrafish for the first time.

  3. Genetic variants in MTNR1B affecting insulin secretion.

    Science.gov (United States)

    Müssig, Karsten; Staiger, Harald; Machicao, Fausto; Häring, Hans-Ulrich; Fritsche, Andreas

    2010-09-01

    The incidence of type 2 diabetes mellitus has markedly increased worldwide over the past decades. Pancreatic beta-cell dysfunction as well as central and peripheral insulin resistance appears to be elementary features in the pathophysiology of type 2 diabetes mellitus. Major environmental conditions predisposing to the development of type 2 diabetes are excessive food intake and sedentary life-style on the background of a genetic predisposition. Recent genome-wide association studies identified several novel type 2 diabetes risk genes, with impaired pancreatic beta-cell function as the underlying mechanism of increased diabetes risk in the majority of genes. Many of the novel type 2 diabetes risk genes, including MTNR1B which encodes one of the two known human melatonin receptors, were unexpected at first glance. However, previous animal as well as human studies already pointed to a significant impact of the melatonin system on the regulation of glucose homeostasis, in addition to its well known role in modulation of sleep and circadian rhythms. This brief review aims to give an overview of how alterations in the melatonin system could contribute to an increased diabetes risk, paying special attention to the role of melatonin receptors in pancreatic beta-cell function.

  4. Exogenous estradiol enhances apoptosis in regressing post-partum rat corpora lutea possibly mediated by prolactin

    Directory of Open Access Journals (Sweden)

    Telleria Carlos M

    2005-08-01

    Full Text Available Abstract Background In pregnant rats, structural luteal regression takes place after parturition and is associated with cell death by apoptosis. We have recently shown that the hormonal environment is responsible for the fate of the corpora lutea (CL. Changing the levels of circulating hormones in post-partum rats, either by injecting androgen, progesterone, or by allowing dams to suckle, was coupled with a delay in the onset of apoptosis in the CL. The objectives of the present investigation were: i to examine the effect of exogenous estradiol on apoptosis of the rat CL during post-partum luteal regression; and ii to evaluate the post-partum luteal expression of the estrogen receptor (ER genes. Methods In a first experiment, rats after parturition were separated from their pups and injected daily with vehicle or estradiol benzoate for 4 days. On day 4 post-partum, animals were sacrificed, blood samples were taken to determine serum concentrations of hormones, and the ovaries were isolated to study apoptosis in situ. In a second experiment, non-lactating rats after parturition received vehicle, estradiol benzoate or estradiol benzoate plus bromoergocryptine for 4 days, and their CL were isolated and used to study apoptosis ex vivo. In a third experiment, we obtained CL from rats on day 15 of pregnancy and from non-lactating rats on day 4 post-partum, and studied the expression of the messenger RNAs (mRNAs encoding the ERalpha and ERbeta genes. Results Exogenous administration of estradiol benzoate induced an increase in the number of apoptotic cells within the CL on day 4 post-partum when compared with animals receiving vehicle alone. Animals treated with the estrogen had higher serum prolactin and progesterone concentrations, with no changes in serum androstenedione. Administration of bromoergocryptine blocked the increase in serum prolactin and progesterone concentrations, and DNA fragmentation induced by the estrogen treatment. ERalpha and

  5. 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.

  6. Zinc Finger Homeodomain Factor Zfhx3 Is Essential for Mammary Lactogenic Differentiation by Maintaining Prolactin Signaling Activity.

    Science.gov (United States)

    Zhao, Dan; Ma, Gui; Zhang, Xiaolin; He, Yuan; Li, Mei; Han, Xueying; Fu, Liya; Dong, Xue-Yuan; Nagy, Tamas; Zhao, Qiang; Fu, Li; Dong, Jin-Tang

    2016-06-10

    The zinc finger homeobox 3 (ZFHX3, also named ATBF1 for AT motif binding factor 1) is a transcription factor that suppresses prostatic carcinogenesis and induces neuronal differentiation. It also interacts with estrogen receptor α to inhibit cell proliferation and regulate pubertal mammary gland development in mice. In the present study, we examined whether and how Zfhx3 regulates lactogenic differentiation in mouse mammary glands. At different stages of mammary gland development, Zfhx3 protein was expressed at varying levels, with the highest level at lactation. In the HC11 mouse mammary epithelial cell line, an in vitro model of lactogenesis, knockdown of Zfhx3 attenuated prolactin-induced β-casein expression and morphological changes, indicators of lactogenic differentiation. In mouse mammary tissue, knock-out of Zfhx3 interrupted lactogenesis, resulting in underdeveloped glands with much smaller and fewer alveoli, reduced β-casein expression, accumulation of large cytoplasmic lipid droplets in luminal cells after parturition, and failure in lactation. Mechanistically, Zfhx3 maintained the expression of Prlr (prolactin receptor) and Prlr-Jak2-Stat5 signaling activity, whereas knockdown and knock-out of Zfhx3 in HC11 cells and mammary tissues, respectively, decreased Prlr expression, Stat5 phosphorylation, and the expression of Prlr-Jak2-Stat5 target genes. These findings indicate that Zfhx3 plays an essential role in proper lactogenic development in mammary glands, at least in part by maintaining Prlr expression and Prlr-Jak2-Stat5 signaling activity.

  7. Protein Tyrosine Phosphatase 1B (PTP1B): A Potential Target for Alzheimer’s Therapy?

    Science.gov (United States)

    Vieira, Marcelo N. N.; Lyra e Silva, Natalia M.; Ferreira, Sergio T.; De Felice, Fernanda G.

    2017-01-01

    Despite significant advances in current understanding of mechanisms of pathogenesis in Alzheimer’s disease (AD), attempts at drug development based on those discoveries have failed to translate into effective, disease-modifying therapies. AD is a complex and multifactorial disease comprising a range of aberrant cellular/molecular processes taking part in different cell types and brain regions. As a consequence, therapeutics for AD should be able to block or compensate multiple abnormal pathological events. Here, we examine recent evidence that inhibition of protein tyrosine phosphatase 1B (PTP1B) may represent a promising strategy to combat a variety of AD-related detrimental processes. Besides its well described role as a negative regulator of insulin and leptin signaling, PTB1B recently emerged as a modulator of various other processes in the central nervous system (CNS) that are also implicated in AD. These include signaling pathways germane to learning and memory, regulation of synapse dynamics, endoplasmic reticulum (ER) stress and microglia-mediated neuroinflammation. We propose that PTP1B inhibition may represent an attractive and yet unexplored therapeutic approach to correct aberrant signaling pathways linked to AD. PMID:28197094

  8. Hyperprolactinemia with normal serum prolactin: Its clinical significance

    Directory of Open Access Journals (Sweden)

    Manika Agarwal

    2010-01-01

    Full Text Available Amenorrhea and infertility with an added feature of galactorrhea makes a provisional diagnosis of hyperprolactinemia. But again, normal serum prolactin with all clinical features of hyperprolactinemia might question the diagnosis and further management. The answer lies in the heterogeneity of the peptide hormone - the immunoactive and the bioactive forms. This has been further illustrated with the help of a case which had been treated with cabergoline.

  9. 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.

  10. Release of oxytocin and prolactin in response to suckling.

    Science.gov (United States)

    McNeilly, A S; Robinson, I C; Houston, M J; Howie, P W

    1983-01-22

    The oxytocin and prolactin responses to suckling were measured in 10 women in early (n = 5) and established lactation (n = 5). Oxytocin was released in a pulsatile manner during suckling in all women, but the response was not related to milk volume, prolactin response, or parity of the mother. In all 10 women plasma oxytocin concentrations increased three to 10 minutes before suckling began. In five women this occurred in response to the baby crying, in three it coincided with the baby becoming restless in expectation of the feed, while in two it corresponded with the mother preparing for the feed. There was no prolactin response to stimuli other than stimulation of the nipple associated with suckling. These results clearly indicate that the milk ejection reflex, with release of oxytocin, occurs in most women before the tactile stimulus of suckling. A second release of oxytocin follows in response to the suckling stimulus itself. Thus it is important that care is taken to protect breast feeding mothers from stress not only during suckling but also immediately before nursing, when conditioned releases of oxytocin will occur.

  11. [Activity of clobazam on plasma prolactin and gonadotropins after administration of sulpiride in the male rat].

    Science.gov (United States)

    Valli, M; Courtiere, A; Tamalet, C; Jadot, G

    1984-01-01

    The acute administration of the 1,5 benzodiazepine clobazam (20 and 100 mg/kg orally) reduces the sulpiride-induced release of prolactin in the male rat. The decrease in prolactin plasma level is respectively of 66 and 75% for the two doses, whereas it has minimal effects on the gonadotropins (FSH and LH). The clobazam induced prolactin lowering effect is compared to the one observed after diazepam administration. Finally, we have shown that the two benzodiazepines have no effect either on prolactin or on gonadotropins, when administered alone.

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

    Science.gov (United States)

    Snowdon, Charles T; Ziegler, Toni E

    2015-01-01

    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.

  13. Effects of vasoactive intestinal peptide on prolactin secretion in three species of passerine birds.

    Science.gov (United States)

    Vleck, C M; Patrick, D J

    1999-01-01

    Previous work on domesticated species has indicated that vasoactive intestinal peptide (VIP) is an important prolactin-releasing factor in these birds, but no comparative work in passerine birds has been reported. This study showed that iv injections of VIP (50-100 microg/kg body mass) result in a dramatic, but transitory, rise in plasma prolactin in Mexican jays (Aphelocoma ultramarina). Significant increases in prolactin were also observed following VIP injection in blue jays (Cyanocitta cristata) and zebra finches (Poephilla guttata). At the dosage we used, maximum levels of prolactin attained were slightly lower (Mexican jays) or very similar (blue jay and zebra finch) to the maximum prolactin levels observed in other, breeding birds of the same species. In zebra finches that initially had low prolactin, VIP injection resulted in a greater than 10-fold increase in prolactin within 10 min, but those individuals that already had elevated prolactin showed no further increase in response to VIP. Slow-release pellets of VIP implanted subcutaneously in Mexican jays and releasing 10 or 15 microg VIP/day (two or three pellets) produced a significant increase in plasma prolactin (78 and 92% rise, respectively) compared to birds with placebo pellets or with with one pellet releasing only 5 microg/day.

  14. 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.

  15. Practical route to the left wing of CTX1B and total syntheses of CTX1B and 54-deoxyCTX1B.

    Science.gov (United States)

    Yamashita, Shuji; Takeuchi, Katsutoshi; Koyama, Takuya; Inoue, Masayuki; Hayashi, Yujiro; Hirama, Masahiro

    2015-02-02

    Ciguatoxins, the principal causative agents of ciguatera seafood poisoning, are extremely large polycyclic ethers. We report herein a reliable route for constructing the left wing of CTX1B, which possesses the acid/base/oxidant-sensitive bisallylic ether moiety, by a 6-exo radical cyclization/ring-closing metathesis strategy. This new route enabled us to achieve the second-generation total synthesis of CTX1B and the first synthesis of 54-deoxyCTX1B.

  16. 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.

  17. Kinetics and Mechanism of Protein Tyrosine Phosphatase 1B (PTP1B) Inactivation by Acrolein

    Science.gov (United States)

    Seiner, Derrick R.; LaButti, Jason N.; Gates, Kent S.

    2010-01-01

    Human cells are exposed to the electrophilic α,β-unsaturated aldehyde acrolein from a variety of sources. Reaction of acrolein with functionally critical protein thiol residues can yield important biological consequences. Protein tyrosine phosphatases (PTPs) are an important class of cysteine-dependent enzymes whose reactivity with acrolein previously has not been well characterized. These enzymes catalyze the dephosphorylation of phosphotyrosine residues on proteins via a phosphocysteine intermediate. PTPs work in tandem with protein tyrosine kinases to regulate a number of critically important mammalian signal transduction pathways. We find that acrolein is a potent time-dependent inactivator of the enzyme PTP1B (kinact = 0.02 ± 0.005 s−1, KI = 2.3 ± 0.6 × 10−4 M). Enzyme activity does not return upon gel filtration of the inactivated enzyme and addition of the competitive phosphatase inhibitor vanadate slows inactivation of PTP1B by acrolein. Together these observations suggest that acrolein covalently modifies the active site of PTP1B. Mass spectrometric analysis reveals that acrolein modifies the catalytic cysteine residue at the active site of the enzyme. Aliphatic aldehydes such as glyoxal, acetaldehyde, and propanal are relatively weak inactivators of PTP1B under the conditions employed here. Similarly, unsaturated aldehydes such as crotonaldehyde and 3-methyl-2-butenal bearing substitution at the alkene terminus are poor inactivators of the enzyme. Overall, the data suggest that enzyme inactivation occurs via conjugate addition of the catalytic cysteine residue to the carbon-carbon double bond of acrolein. The results indicate that inactivation of PTPs should be considered as a possible contributor to the diverse biological activities of acrolein and structurally-related α,β-unsaturated aldehydes. PMID:17655273

  18. Hypoglycemic effect of Astragalus polysaccharide and its effect on PTP1B

    Institute of Scientific and Technical Information of China (English)

    Yong WU; Jing-ping OU-YANG; Ke WU; Ya WANG; Yun-feng ZHOU; Chong-yuan WEN

    2005-01-01

    Aim: To examine the effects ofAstragalus polysaccharide (APS), a component of an aqueous extract of Astragalus membranaceus roots, on protein tyrosine phosphatase 1B (PTP1B), a negative regulator of insulin-receptor (IR) signal transduction, and its potential role in the amelioration of insulin resistance.Methods: Ten-week-old fat-fed streptozotocin (STZ)-treated rats, an animal model of type Ⅱ diabetes mellitus (TIIDM), were treated with APS (400 mg/kg po) for 5 weeks. Insulin sensitivity was identified by the insulin-tolerance test. Further analyses on the possible changes in insulin signaling occurring in skeletal muscle and liver were performed by immunoprecipitation or Western blotting. PTP1B activity was measured by an assay kit. Results: The diabetic rats responded to APS with a significant decrease in body weight, plasma glucose, and improved insulin sensitivity. The activity and expression of PTP1B were elevated in the skeletal muscle and liver of TIIDM rats. Thus the insulin signaling in target tissues was diminished. APS reduced both PTP1B protein level and activity in the muscle,but not in the liver of TIIDM rats. Insulin-induced tyrosine phosphorylation of the IR β-subunit and insulin receptor substrate-1 (IRS-1) were increased in the muscle,but not in the liver of APS-treated TIIDM rats. There was no change in the activity or expression of PTP1B in APS-treated normal rats, and blood insulin levels did not change in TIIDM rats after treatment with APS. Conclusion: APS enables insulin-sensitizing and hypoglycemic activity at least in part by decreasing the elevated expression and activity of PTP1B in the skeletal muscles of TIIDM rats.

  19. Main: 1B5Q [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B5Q トウモロコシ Corn Zea mays L. Polyamine Oxidase Precursor Name=Pao; Zea Mays Molecul...EESRRIEQQSDEQTKAEIMQVLRKMFPGKDVPDATDILVPRWWSDRFYKGTFSNWPVGVNRYEYDQLRAPVGRVYFTGEHTSEHYNGYVHGAYLSGIDSAEILINCAQKKMCKYHVQGKYD corn_1B5Q.jpg ...

  20. Knockdown of Lingo1b protein promotes myelination and oligodendrocyte differentiation in zebrafish.

    Science.gov (United States)

    Yin, Wu; Hu, Bing

    2014-01-01

    Demyelinating diseases include multiple sclerosis, which is a neurodegenerative disease characterized by immune attacks on the central nervous system (CNS), resulting in myelin sheath damage and axonal loss. Leucine-rich repeat and immunoglobulin domain-containing neurite outgrowth inhibitory protein (Nogo) receptor-interacting protein-1 (LINGO-1) have been identified as a negative regulator of oligodendrocytes differentiation. Targeted LINGO-1 inhibition promotes neuron survival, axon regeneration, oligodendrocyte differentiation, and remyelination in diverse animal models. Although studies in rodent models have extended our understanding of LINGO-1, its roles in neural development and myelination in zebrafish (Danio rerio) are not yet clear. In this study, we cloned the zebrafish homolog of the human LINGO-1 and found that lingo1b regulated myelination and oligodendrocyte differentiation. The expression of lingo1b started 1 (mRNA) and 2 (protein) days post-fertilization (dpf) in the CNS. Morpholino oligonucleotide knockdown of lingo1b resulted in developmental abnormalities, including less dark pigment, small eyes, and a curly spinal cord. The lack of lingo1b enhanced myelination and oligodendrocyte differentiation during embryogenesis. Furthermore, immunohistochemistry and movement analysis showed that lingo1b was involved in the axon development of primary motor neurons. These results suggested that Lingo1b protein functions as a negative regulator of myelination and oligodendrocyte differentiation during zebrafish development.

  1. Interaction between the glutamate transporter GLT1b and the synaptic PDZ domain protein PICK1

    DEFF Research Database (Denmark)

    Bassan, Merav; Liu, Hongguang; Madsen, Kenneth L

    2008-01-01

    with the PDZ domain protein PICK1, which plays a critical role in regulating the expression of glutamate receptors at excitatory synapses. A yeast two-hybrid screen of a neuronal library using the carboxyl tail of GLT1b yielded clones expressing PICK1. The GLT1b C-terminal peptide bound to PICK1 with high...... affinity (K(i) = 6.5 +/- 0.4 microM) in an in vitro fluorescence polarization assay. We also tested peptides based on other variants of GLT1 and other glutamate transporters. GLT1b co-immunoprecipitated with PICK1 from rat brain lysates and COS7 cell lysates derived from cells transfected with plasmids...... expressing PICK1 and GLT1b. In addition, expression of GLT1b in COS7 cells changed the distribution of PICK1, bringing it to the surface. GLT1b and PICK1 co-localized with each other and with synaptic markers in hippocampal neurons in culture. Phorbol ester, an activator of protein kinase C (PKC), a known...

  2. Association of PTP1B with Outcomes of Breast Cancer Patients Who Underwent Neoadjuvant Chemotherapy

    Science.gov (United States)

    Rivera Franco, Monica M.; Leon Rodriguez, Eucario; Martinez Benitez, Braulio; Villanueva Rodriguez, Luisa G.; de la Luz Sevilla Gonzalez, Maria; Armengol Alonso, Alejandra

    2016-01-01

    PTP1B is involved in the oncogenesis of breast cancer. In addition, neoadjuvant therapy has been widely used in breast cancer; thus, a measurement to assess survival improvement could be pathological complete response (pCR). Our objective was to associate PTP1B overexpression with outcomes of breast cancer patients who underwent neoadjuvant chemotherapy. Forty-six specimens were included. Diagnostic biopsies were immunostained using anti-PTP1B antibody. Expression was categorized as negative (<5%) and overexpression (≥5%). Patients’ responses were graded according to the Miller–Payne system. Sixty-three percent of patients overexpressed PTP1B. There was no significant association between PTP1B overexpression and pCR (P = 0.2). However, when associated with intrinsic subtypes, overexpression was higher in human epidermal growth factor receptor 2-positive-enriched specimens (P = 0.02). Ten-year progression-free survival showed no differences. Our preliminary results do not show an association between PTP1B over-expression and pCR; however, given the limited sample and heterogeneous treatment in our cohort, this hypothesis cannot be excluded. PMID:27840578

  3. Modulating the strength and threshold of NOTCH oncogenic signals by mir-181a-1/b-1.

    Directory of Open Access Journals (Sweden)

    Rita Fragoso

    Full Text Available Oncogenes, which are essential for tumor initiation, development, and maintenance, are valuable targets for cancer therapy. However, it remains a challenge to effectively inhibit oncogene activity by targeting their downstream pathways without causing significant toxicity to normal tissues. Here we show that deletion of mir-181a-1/b-1 expression inhibits the development of Notch1 oncogene-induced T cell acute lymphoblastic leukemia (T-ALL. mir-181a-1/b-1 controls the strength and threshold of Notch activity in tumorigenesis in part by dampening multiple negative feedback regulators downstream of NOTCH and pre-T cell receptor (TCR signaling pathways. Importantly, although Notch oncogenes utilize normal thymic progenitor cell genetic programs for tumor transformation, comparative analyses of mir-181a-1/b-1 function in normal thymocyte and tumor development demonstrate that mir-181a-1/b-1 can be specifically targeted to inhibit tumor development with little toxicity to normal development. Finally, we demonstrate that mir-181a-1/b-1, but not mir-181a-2b-2 and mir-181-c/d, controls the development of normal thymic T cells and leukemia cells. Together, these results illustrate that NOTCH oncogene activity in tumor development can be selectively inhibited by targeting the molecular networks controlled by mir-181a-1/b-1.

  4. Prolactin gene polymorphism (-1149 G/T) is associated with hyperprolactinemia in patients with schizophrenia treated with antipsychotics

    NARCIS (Netherlands)

    Ivanova, Svetlana A; Osmanova, Diana Z; Boiko, Anastasia S; Pozhidaev, Ivan V; Freidin, Maxim B; Fedorenko, Olga Yu; Semke, Arkadiy V; Bokhan, Nikolay A; Kornetova, Elena G; Rakhmazova, Lubov D; Wilffert, Bob; Loonen, Antonius

    2016-01-01

    BACKGROUND: Antipsychotic drugs can cause hyperprolactinemia. However, hyperprolactinemia was also observed in treatment-naive patients with a first schizophrenic episode. This phenomenon might be related to the role of prolactin as a cytokine in autoimmune diseases. Extrapituitary prolactin product

  5. Antipsychotic Medication in Children and Adolescents : A Descriptive Review of the Effects on Prolactin Level and Associated Side Effects

    NARCIS (Netherlands)

    Roke, Yvette; van Harten, Peter N.; Boot, Annemieke M.; Buitelaar, Jan K.

    2009-01-01

    Objective: This review reports the incidence of hyperprolactinemia, its relationship with genotype, and prolactin-related side effects in children and adolescents treated with antipsychotics. Method: Data on prolactin levels were available for haloperidol, pimozide, risperidone, olanzapine, clozapin

  6. Antipsychotic medication in children and adolescents: a descriptive review of the effects on prolactin level and associated side effects.

    NARCIS (Netherlands)

    Roke, Y.; Harten, P.N. van; Boot, A.M.; Buitelaar, J.K.

    2009-01-01

    OBJECTIVE: This review reports the incidence of hyperprolactinemia, its relationship with genotype, and prolactin-related side effects in children and adolescents treated with antipsychotics. METHOD: Data on prolactin levels were available for haloperidol, pimozide, risperidone, olanzapine, clozapin

  7. 18 CFR 1b.11 - Limitation on participation.

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    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Limitation on participation. 1b.11 Section 1b.11 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.11 Limitation...

  8. 18 CFR 1b.3 - Scope of investigations.

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    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Scope of investigations. 1b.3 Section 1b.3 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.3 Scope of investigations....

  9. 18 CFR 1b.8 - Requests for Commission investigations.

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  10. 18 CFR 1b.7 - Procedure after investigation.

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  11. 18 CFR 1b.18 - Right to submit statements.

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  12. 18 CFR 1b.9 - Confidentiality of investigations.

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  13. 18 CFR 1b.4 - Types of investigations.

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  14. 18 CFR 1b.10 - By whom conducted.

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  15. GD1b-specific antibodies may bind to complex of GQ1b and GM1, causing ataxia.

    Science.gov (United States)

    Yuki, Nobuhiro; Fukami, Yuki; Yanaka, Chiaki; Koike, Saiko; Hirata, Koichi

    2014-08-01

    Monospecific IgG antibodies to GD1b ganglioside (GD1b-specific antibodies) have been found in patients with acute ataxic neuropathy and Guillain-Barré syndrome, but the association of the GD1b-specific antibodies with specific neurological conditions has yet to be established. We tested sera from more than 10,000 patients with various neurological disorders, and found six sera, which contained IgG antibodies to GD1b, but not to LM1, GM1, GM1b, GD1a, GalNAc-GD1a, GT1a, GT1b and GQ1b. All six patients who carried GD1b-specific antibodies presented with acute onset of ataxia and monophasic course of the illness, of whom five demonstrated cerebellar-like ataxia. Four patients had antecedent symptoms of upper respiratory tract infection. The six patients demonstrated areflexia, and four complained of distal numbness. All the six patients who had the GD1b-specific antibodies carried IgG antibodies to complex of GQ1b/GM1 and GT1a/GM1. GD1b-specific antibodies were significantly absorbed by GQ1b/GM1 and GT1a/GM1 and anti-GQ1b/GM1 and -GT1a/GM1 antibodies were absorbed by GD1b. In conclusion, the GD1b-specific antibodies, which recognizes GQ1b/GM1 or GT1a/GM1 complex, are associated with acute ataxia.

  16. Effect of ghrelin and thyrotropin-releasing hormone on prolactin secretion in normal women.

    Science.gov (United States)

    Messini, C I; Dafopoulos, K; Chalvatzas, N; Georgoulias, P; Anifandis, G; Messinis, I E

    2010-03-01

    It is known that ghrelin stimulates the secretion of prolactin in women. The aim of this study was to examine the effect of exogenous thyrotropin-releasing hormone (TRH) on ghrelin-induced prolactin release. Ten healthy normally cycling women were studied in four menstrual cycles. The women were injected intravenously in late follicular phase (follicle size 16-17 mm) with a single dose of normal saline (cycle 1), ghrelin (1 microg/kg) (cycle 2), thyrotropin-releasing hormone (200 microg) (cycle 3), and ghrelin plus thyrotropin-releasing hormone (cycle 4). Blood samples in relation to saline or drugs injection (time 0) were taken at -15, 0, 15, 30, 45, 60, 75, 90, and 120 min. The prolactin and growth hormone responses were assessed. After ghrelin administration (cycles 2 and 4), plasma ghrelin, serum prolactin, and growth hormone levels increased rapidly, peaking at 15-30 min (psecretion markedly (pGhrelin induced a smaller prolactin increase than thyrotropin-releasing hormone (pghrelin and thyrotropin-releasing hormone induced a similar increase in prolactin levels as with thyrotropin-releasing hormone alone. No changes in growth hormone and prolactin levels were seen after saline injection. These results demonstrate that the stimulating effect of ghrelin on prolactin secretion is not additive with that of thyrotropin-releasing hormone.

  17. 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.

  18. Prolactin release in children treated with risperidone - Impact and role of CYP2D6 metabolism

    NARCIS (Netherlands)

    Troost, Pieter W.; Lahuis, Bertine E.; Hermans, Mirjam H.; Buitelaar, Jan K.; van Engeland, Herman; Scahill, Lawrence; Minderaa, Ruud B.; Hoekstra, Pieter J.

    2007-01-01

    Objective: Little is known about the role of CYP2136 polymorphism in risperidone-induced prolactin release in children. Method: Twenty-five children (aged 5-15 years) with pervasive developmental disorders were genotyped for CYP2D6 polymorphisms. Serum prolactin, risperidone, and 9-hydroxyrisperidon

  19. 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 hemip

  20. Analysis list: HNF1B [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available HNF1B Adipocyte,Digestive tract,Pluripotent stem cell + hg19 http://dbarchive.biosc...iencedbc.jp/kyushu-u/hg19/target/HNF1B.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/HNF1B.5....tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/HNF1B.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/HNF1...B.Adipocyte.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/HNF1...B.Digestive_tract.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/HNF1B.Pluripotent_st

  1. EGF stimulates Pit-1 independent transcription of the human prolactin pituitary promoter in human breast cancer SK-BR-3 cells through its proximal AP-1 response element.

    Science.gov (United States)

    Manfroid, Isabelle; Van de Weerdt, Cécile; Baudhuin, Ariane; Martial, Joseph A; Muller, Marc

    2005-01-14

    Normal and neoplastic human mammary gland cells are targets for the proliferative action of prolactin. These cells also synthesize prolactin, thereby inducing an autocrine/paracrine proliferative loop. We present the first extensive analysis of the transcriptional regulation of the human prolactin gene (hPRL) in human mammary tumor cells, SK-BR-3. We show that the pituitary promoter is functional in these cells in the absence of the pituitary-specific factor Pit-1. Expression of exogenous Pit-1 or epidermal growth factor (EGF) treatment stimulates the transfected hPRL pituitary promoter and the endogenous hPRL expression. EGF stimulation is mediated by increased synthesis of c-fos and c-jun, resulting in AP-1 binding to the proximal hPRL pituitary promoter. This regulation involves the EGF receptor, possibly ErbB2 that is highly expressed in SK-BR-3 cells, and a PI3K/JNK pathway. The stimulation of hPRL gene transcription by EGF in mammary cells may include hPRL in a complex regulatory network controlling growth of human mammary cells.

  2. Lower baseline plasma cortisol and prolactin together with increased body temperature and higher mCPP-induced cortisol responses in men with pedophilia.

    Science.gov (United States)

    Maes, M; van West, D; De Vos, N; Westenberg, H; Van Hunsel, F; Hendriks, D; Cosyns, P; Scharpé, S

    2001-01-01

    There is some evidence that hormonal and serotonergic alterations may play a role in the pathophysiology of paraphilias. The aims of the present study were to examine: 1) baseline plasma cortisol, plasma prolactin, and body temperature; and 2) cortisol, prolactin, body temperature, as well as behavioral responses to meta-chlorophenylpiperazine (mCPP) and placebo in pedophiles and normal men. Pedophiles showed significantly lower baseline plasma cortisol and prolactin concentrations and a higher body temperature than normal volunteers. The mCPP-induced cortisol responses were significantly greater in pedophiles than in normal volunteers. In normal volunteers, mCPP-induced a hyperthermic response, whereas in pedophiles no such response was observed. mCPP induced different behavioral responses in pedophiles than in normal men. In pedophiles, but not in normal men, mCPP increased the sensations "feeling dizzy, " "restless," and "strange" and decreased the sensation "feeling hungry". The results suggest that there are several serotonergic disturbances in pedophiles. It is hypothesized that the results are compatible with a decreased activity of the serotonergic presynaptic neuron and a 5-HT2 postsynaptic receptor hyperresponsivity.

  3. Prolactin is associated with metabolic risk and cortisol in 1007 women with polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Altinok, Magda; Mumm, Hanne

    2014-01-01

    . PARTICIPANTS/MATERIALS, SETTING, METHODS: Serum prolactin levels were measured along with a clinical evaluation (Ferriman-Gallwey score, BMI, waist circumference, blood pressure) plus hormone analyses (sex hormones, fasting lipids, insulin, glucose), transvaginal ultrasound, and oral glucose tolerance (n = 234.......001). In the patient population prolactin levels were inversely associated with age, smoking status, waist circumference, total cholesterol, triglyceride and low-density lipoprotein (LDL) and positively associated with high-density lipoprotein, estradiol, total testosterone, dehydroepiandrosterone sulfate, 17......STUDY QUESTION: Is there an association between prolactin and markers of metabolic risk in polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Low serum prolactin was a metabolic risk marker in PCOS. WHAT IS KNOWN ALREADY: Prolactin is routinely measured to exclude endocrine diseases in PCOS. Recent...

  4. Prolactin as a Candidate Gene Controlling Molting and Egg Production of Duck

    Directory of Open Access Journals (Sweden)

    Triana Susanti

    2015-03-01

    Full Text Available Incidence of molting is a crucial problem in the local ducks that need to be handled from many aspects including genetic aspect. Handling of molting genetically can be done quickly and accurately when the control genes have been found. The search for marker genes of molting can be conducted in poultry through broodiness naturally, because its physiological processes are related to the continuity of egg production. This paper describes the mechanism of molting, the relationship of molting with prolactin hormone and the association of prolactin gene polymorphism with molting and egg production. Molting and egg production were influenced by the prolactin hormone, that may be controlled by the prolactin gene. High concentration of prolactin hormone will inhibit the function of pituitary gland, decreasing production of gonadotrophin hormone (follicle stimulating hormone and luteinizing hormone hence ovulation ceased. This will stop egg production and at the same time molting proccess occurred.

  5. Neuroendocrine regulation of prolactin secretion during late pregnancy: easing the transition into lactation.

    Science.gov (United States)

    Andrews, Z B

    2005-07-01

    Prolactin is an anterior pituitary hormone critical for maintaining pregnancy and lactation. Under normal conditions, prolactin secretion is tightly regulated by inhibitory dopaminergic neuronal systems within the mediobasal hypothalamus in a process known as short-loop negative feedback. This review focuses on neuroendocrine adaptations to prolactin negative feedback during late pregnancy. It is suggested that, in terms of prolactin regulation, late pregnancy is a transition period into lactation because many of the neuroendocrine adaptations promoting hyperprolactinemia in lactation develop during late pregnancy. As a consequence, the maternal brain is geared to provide unrestrained prolactin release critical for milk production, maternal care and thus survival of the offspring before parturition. The mechanisms responsible for these changes are discussed.

  6. Immunoreactive prolactin in breast milk and plasma of women with hyperprolactinemia, galactorrhea and menstrual dysfunction.

    Science.gov (United States)

    Yuen, B H

    1986-01-01

    Prolactin levels were measured by radioimmunoassay in paired breast milk and plasma samples of 11 hyperprolactinemic women with galactorrhea and various menstrual disorders (amenorrhea, n = 8; oligomenorrhea, n = 2; luteal phase defect, n = 1) before and during treatment with bromocriptine (Parlodel, Sandoz). Pretreatment levels of prolactin in the milk and plasma were 80 +/- 13 ng/mL (mean +/- SEM) and 47 +/- 7 ng/mL (P less than 0.05), respectively. While on treatment, the concentration gradient for prolactin remained in favour of the milk, with values for milk and plasma 59 +/- 11 and 29 +/- 3 ng/mL (P less than 0.01), respectively. Thus, bromocriptine lowered the prolactin concentrations in both breast milk and plasma. Since prolactin in milk is biologically active, these findings may be relevant to the initiation and maintenance of lactation in women with abnormal lactogenesis.

  7. Neonatal Treatment with Antiserum to Prolactin Lowers Blood Pressure in Rats

    Science.gov (United States)

    Mills, David E.; Buckman, Maire T.; Peake, Glenn T.

    1982-07-01

    Prolactin administration reportedly increases blood pressure in rats and rabbits. To study the effects of prolactiin deficiency on blood pressure, rats were given saline, normal rabbit serum, or rabbit antiserum to rat prolactin on postnatal days 2 to 5. Both males and females given antiserum had significantly lower blood pressure at 14 weeks than rats given saline or normal rabbit serum. Blood pressure differences between females given antiserum and females given saline disappeared during and following pregnancy. The antiserum also lowered the concentration of prolactin in plasma 49 percent in males and decreased the prolactin response to ether stress in both sexes. These results suggest that endogenous prolactin is involved in blood pressure regulation.

  8. [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.

  9. Injectable interferon beta-1b for the treatment of relapsing forms of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Slobodan M Jankovic

    2010-03-01

    Full Text Available Slobodan M JankovicPharmacology Department, Medical Faculty, University of Kragujevac, Kragujevac, SerbiaAbstract: Multiple sclerosis (MS is chronic inflammatory and demyelinating disease with either a progressive (10%–15% or relapsing-remitting (85%–90% course. The pathological hallmarks of MS are lesions of both white and grey matter in the central nervous system. The onset of the disease is usually around 30 years of age. The patients experience an acute focal neurologic dysfunction which is not characteristic, followed by partial or complete recovery. Acute episodes of neurologic dysfunction with diverse signs and symptoms will then recur throughout the life of a patient, with periods of partial or complete remission and clinical stability in between. Currently, there are several therapeutic options for MS with disease-modifying properties. Immunomodulatory therapy with interferon beta-1b (IFN-β1b or -1a, glatiramer and natalizumab shows similar efficacy; in a resistant or intolerant patient, the most recently approved therapeutic option is mitoxantrone. IFN-β1b in patients with MS binds to specific receptors on surface of immune cells, changing the expression of several genes and leading to a decrease in quantity of cell-associated adhesion molecules, inhibition of major histocompatibility complex class II expression and reduction in inflammatory cells migration into the central nervous system. After 2 years of treatment, IFN-β1b reduces the risk of development of clinically defined MS from 45% (with placebo to 28% (with IFN-β1b. It also reduces relapses for 34% (1.31 exacerbations annually with placebo and 0.9 with higher dose of IFN-β1b and makes 31% more patients relapse-free. In secondary-progressive disease annual rate of progression is 3% lower with IFN-β1b. In recommended doses IFN-β1b causes the following frequent adverse effects: injection site reactions (redness, discoloration, inflammation, pain, necrosis and non

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1986-08-01

    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 (diC8), 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 M. Diolein (100 M), 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 4US -phorbol 12,13-dibutyrate, which activate protein kinase C in other systems, also inhibited the release of prolactin, which the protein kinase C inactivate 4 -phorbol-12,13-didecanoate was without effect. The inhibition of prolactin release was secondary to a decrease in prolactin synthesis. Although diC8 and PMA inhibited the synthesis and release of prolactin, these agents had no effect on the synthesis or release of trichloroacetic acid-precipitable (TVS)methionine-labeled decidual proteins and did not cause the release of the cytosolic enzymes lactic dehydrogenase and alkaline phosphatase. DiC8 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 diC8 and phorbol esters strongly implicates protein kinase C in the regulation of the production and release of prolactin from the decidua.

  11. Selectivity and potency of microcystin congeners against OATP1B1 and OATP1B3 expressing cancer cells.

    Directory of Open Access Journals (Sweden)

    Timo H J Niedermeyer

    Full Text Available Microcystins are potent phosphatase inhibitors and cellular toxins. They require active transport by OATP1B1 and OATP1B3 transporters for uptake into human cells, and the high expression of these transporters in the liver accounts for their selective hepatic toxicity. Several human tumors have been shown to have high levels of expression of OATP1B3 but not OATP1B1, the main transporter in liver cells. We hypothesized that microcystin variants could be isolated that are transported preferentially by OATP1B3 relative to OATP1B1 to advance as anticancer agents with clinically tolerable hepatic toxicity. Microcystin variants have been isolated and tested for cytotoxicity in cancer cells stably transfected with OATP1B1 and OATP1B3 transporters. Microcystin variants with cytotoxic OATP1B1/OATP1B3 IC50 ratios that ranged between 0.2 and 32 were found, representing a 150-fold range in transporter selectivity. As microcystin structure has a significant impact on transporter selectivity, it is potentially possible to develop analogs with even more pronounced OATP1B3 selectivity and thus enable their development as anticancer drugs.

  12. Selectivity and potency of microcystin congeners against OATP1B1 and OATP1B3 expressing cancer cells.

    Science.gov (United States)

    Niedermeyer, Timo H J; Daily, Abigail; Swiatecka-Hagenbruch, Monika; Moscow, Jeffrey A

    2014-01-01

    Microcystins are potent phosphatase inhibitors and cellular toxins. They require active transport by OATP1B1 and OATP1B3 transporters for uptake into human cells, and the high expression of these transporters in the liver accounts for their selective hepatic toxicity. Several human tumors have been shown to have high levels of expression of OATP1B3 but not OATP1B1, the main transporter in liver cells. We hypothesized that microcystin variants could be isolated that are transported preferentially by OATP1B3 relative to OATP1B1 to advance as anticancer agents with clinically tolerable hepatic toxicity. Microcystin variants have been isolated and tested for cytotoxicity in cancer cells stably transfected with OATP1B1 and OATP1B3 transporters. Microcystin variants with cytotoxic OATP1B1/OATP1B3 IC50 ratios that ranged between 0.2 and 32 were found, representing a 150-fold range in transporter selectivity. As microcystin structure has a significant impact on transporter selectivity, it is potentially possible to develop analogs with even more pronounced OATP1B3 selectivity and thus enable their development as anticancer drugs.

  13. Ca(2+)-dependent anti-GQ1b antibody in GQ1b-seronegative Fisher syndrome and related disorders.

    Science.gov (United States)

    Uchibori, Ayumi; Gyohda, Atsuko; Chiba, Atsuro

    2016-09-15

    Although serum IgG anti-ganglioside GQ1b antibody is the most specific biomarker for Fisher syndrome and its related disorders (FS-RD), 10%-30% of the patients are still negative in conventional assays ("GQ1b-seronegative") and the relationship between GQ1b-seropositive and -seronegative patients has been unclear. Some molecules require Ca(2+) cations to interact with their ligands (Ca(2+)-dependency). Here we have investigated whether Ca(2+)-dependency is also present in anti-GQ1b antibodies in FS-RD, especially in the GQ1b-seronegative patients and show that IgG antibodies against GQ1b-related antigens (isolated GQ1b and GQ1b-containing complexes) are detected Ca(2+)-dependently in the majority of GQ1b-seronegative patients with FS-RD. The Ca(2+)-dependent antibodies might react specifically with GQ1b-Ca(2+) conformation. This is the first demonstration of disease-related Ca(2+)-dependent antibodies in neurological field. GQ1b-related pathology would be involved in FS-RD more extensively than previously revealed.

  14. Functional modulation of the glutamate transporter variant GLT1b by the PDZ domain protein PICK1

    DEFF Research Database (Denmark)

    Søgaard, Rikke; Borre, Lars; Braunstein, Thomas H

    2013-01-01

    The dominant glutamate transporter isoform in the mammalian brain, GLT1, exists as at least three splice variants, GLT1a, GLT1b, and GLT1c. GLT1b interacts with the scaffold protein PICK1 (protein interacting with kinase C1), which is implicated in glutamatergic neurotransmission via its regulatory...... effect on trafficking of AMPA-type glutamate receptors. The 11 extreme C-terminal residues specific for the GLT1b variant are essential for its specific interaction with the PICK1 PDZ domain, but a functional consequence of this interaction has remained unresolved. To identify a functional effect of PICK......1 on GLT1a or GLT1b separately, we employed the Xenopus laevis expression system. GLT1a and GLT1b displayed similar electrophysiological properties and EC50 for glutamate. Co-expressed PICK1 localized efficiently to the plasma membrane and resulted in a 5-fold enhancement of the leak current in GLT1...

  15. A complex selection signature at the human AVPR1B gene

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    Cagliani Rachele

    2009-06-01

    Full Text Available Abstract Background The vasopressin receptor type 1b (AVPR1B is mainly expressed by pituitary corticotropes and it mediates the stimulatory effects of AVP on ACTH release; common AVPR1B haplotypes have been involved in mood and anxiety disorders in humans, while rodents lacking a functional receptor gene display behavioral defects and altered stress responses. Results Here we have analyzed the two exons of the gene and the data we present suggest that AVPR1B has been subjected to natural selection in humans. In particular, analysis of exon 2 strongly suggests the action of balancing selection in African populations and Europeans: the region displays high nucleotide diversity, an excess of intermediate-frequency alleles, a higher level of within-species diversity compared to interspecific divergence and a genealogy with common haplotypes separated by deep branches. This relatively unambiguous situation coexists with unusual features across exon 1, raising the possibility that a nonsynonymous variant (Gly191Arg in this region has been subjected to directional selection. Conclusion Although the underlying selective pressure(s remains to be identified, we consider this to be among the first documented examples of a gene involved in mood disorders and subjected to natural selection in humans; this observation might add support to the long-debated idea that depression/low mood might have played an adaptive role during human evolution.

  16. receptores

    Directory of Open Access Journals (Sweden)

    Salete Regina Daronco Benetti

    2006-01-01

    Full Text Available Se trata de un estudio etnográfico, que tuvo lo objetivo de interpretar el sistema de conocimiento y del significado atribuidos a la sangre referente a la transfusión sanguínea por los donadores y receptores de un banco de sangre. Para la colecta de las informaciones se observaron los participantes y la entrevista etnográfica se realizó el análisis de dominio, taxonómicos y temáticos. Los dominios culturales fueron: la sangre es vida: fuente de vida y alimento valioso; creencias religiosas: fuentes simbólicas de apoyos; donación sanguínea: un gesto colaborador que exige cuidarse, gratifica y trae felicidad; donación sanguínea: fuente simbólica de inseguridad; estar enfermo es una condición para realizar transfusión sanguínea; transfusión sanguínea: esperanza de vida; Creencias populares: transfusión sanguínea como riesgo para la salud; donadores de sangre: personas benditas; donar y recibir sangre: como significado de felicidad. Temática: “líquido precioso que origina, sostiene, modifica la vida, provoca miedo e inseguridad”.

  17. Intranuclear targeting and nuclear export of the adenovirus E1B-55K protein are regulated by SUMO1 conjugation

    OpenAIRE

    Kindsmüller, Kathrin; Groitl, Peter; Härtl, Barbara; Blanchette, Paola; Hauber, Joachim; Dobner, Thomas

    2007-01-01

    We have investigated the requirements for CRM1-mediated nuclear export and SUMO1 conjugation of the adenovirus E1B-55K protein during productive infection. Our data show that CRM1 is the major export receptor for E1B-55K in infected cells. Functional inactivation of the E1B-55K CRM1-dependent nuclear export signal (NES) or leptomycin B treatment causes an almost complete redistribution of the viral protein from the cytoplasm to the nucleus and its accumulation at the periphery of the viral re...

  18. Seasonally Changing Cryptochrome 1b Expression in the Retinal Ganglion Cells of a Migrating Passerine Bird.

    Directory of Open Access Journals (Sweden)

    Christine Nießner

    Full Text Available Cryptochromes, blue-light absorbing proteins involved in the circadian clock, have been proposed to be the receptor molecules of the avian magnetic compass. In birds, several cryptochromes occur: Cryptochrome 2, Cryptochrome 4 and two splice products of Cryptochrome 1, Cry1a and Cry1b. With an antibody not distinguishing between the two splice products, Cryptochrome 1 had been detected in the retinal ganglion cells of garden warblers during migration. A recent study located Cry1a in the outer segments of UV/V-cones in the retina of domestic chickens and European robins, another migratory species. Here we report the presence of cryptochrome 1b (eCry1b in retinal ganglion cells and displaced ganglion cells of European Robins, Erithacus rubecula. Immuno-histochemistry at the light microscopic and electron microscopic level showed eCry1b in the cell plasma, free in the cytosol as well as bound to membranes. This is supported by immuno-blotting. However, this applies only to robins in the migratory state. After the end of the migratory phase, the amount of eCry1b was markedly reduced and hardly detectable. In robins, the amount of eCry1b in the retinal ganglion cells varies with season: it appears to be strongly expressed only during the migratory period when the birds show nocturnal migratory restlessness. Since the avian magnetic compass does not seem to be restricted to the migratory phase, this seasonal variation makes a role of eCry1b in magnetoreception rather unlikely. Rather, it could be involved in physiological processes controlling migratory restlessness and thus enabling birds to perform their nocturnal flights.

  19. AMYLOID-β PEPTIDE BINDS TO MICROTUBULE-ASSOCIATED PROTEIN 1B (MAP1B)

    Science.gov (United States)

    Gevorkian, Goar; Gonzalez-Noriega, Alfonso; Acero, Gonzalo; Ordoñez, Jorge; Michalak, Colette; Munguia, Maria Elena; Govezensky, Tzipe; Cribbs, David H.; Manoutcharian, Karen

    2008-01-01

    Extracellular and intraneuronal formation of amyloid-beta aggregates have been demonstrated to be involved in the pathogenesis of Alzheimer’s disease. However, the precise mechanism of amyloid-beta neurotoxicity is not completely understood. Previous studies suggest that binding of amyloid-beta to a number of targets have deleterious effects on cellular functions. In the present study we have shown for the first time that amyloid-beta 1-42 bound to a peptide comprising the microtubule binding domain of the heavy chain of microtubule-associated protein 1B by the screening of a human brain cDNA library expressed on M13 phage. This interaction may explain, in part, the loss of neuronal cytoskeletal integrity, impairment of microtubule-dependent transport and synaptic dysfunction observed previously in Alzheimer’s disease. PMID:18079022

  20. Curated human hyperbilirubinemia data and the respective OATP1B1 and 1B3 inhibition predictions.

    Science.gov (United States)

    Kotsampasakou, Eleni; Escher, Sylvia E; Ecker, Gerhard F

    2017-04-01

    Hyperbilirubinemia is a pathological condition, very often indicative of underlying liver condition that is characterized by excessive accumulation of conjugated or unconjugated bilirubin in sinusoidal blood. In literature there are several indications associating the inhibition of the basolateral hepatic transporters Organic anion transporting polypeptide 1B1 and 1B3 (OATP1B1 and 1B3) with hyperbilirubinemia. In this article, we present a curated human hyperbilirubinemia dataset and the respective OATP1B1 and 1B3 inhibition predictions obtained from an effort to generate a classification model for hyperbilirubinemia. These data originate from the research article "Linking organic anion transporting polypeptide 1b1 and 1b3 (oatp1b1 and oatp1b3) interaction profiles to hepatotoxicity- the hyperbilirubinemia use case" (E. Kotsampasakou, S.E. Escher, G.F. Ecker, 2017) [1]. We further provide the full list of descriptors used for generating the hyperbilirubinemia classification models as well as the calculated descriptors for each compound of the dataset that was used to build the classification model.

  1. Clock gene modulates roles of OXTR and AVPR1b genes in prosociality.

    Directory of Open Access Journals (Sweden)

    Haipeng Ci

    Full Text Available BACKGROUND: The arginine vasopressin receptor (AVPR and oxytocin receptor (OXTR genes have been demonstrated to contribute to prosocial behavior. Recent research has focused on the manner by which these simple receptor genes influence prosociality, particularly with regard to the AVP system, which is modulated by the clock gene. The clock gene is responsible for regulating the human biological clock, affecting sleep, emotion and behavior. The current study examined in detail whether the influences of the OXTR and AVPR1b genes on prosociality are dependent on the clock gene. METHODOLOGY/PRINCIPAL FINDINGS: This study assessed interactions between the clock gene (rs1801260, rs6832769 and the OXTR (rs1042778, rs237887 and AVPR1b (rs28373064 genes in association with individual differences in prosociality in healthy male Chinese subjects (n = 436. The Prosocial Tendencies Measure (PTM-R was used to assess prosociality. Participants carrying both the GG/GA variant of AVPR1b rs28373064 and the AA variant of clock rs6832769 showed the highest scores on the Emotional PTM. Carriers of both the T allele of OXTR rs1042778 and the C allele of clock rs1801260 showed the lowest total PTM scores compared with the other groups. CONCLUSIONS: The observed interaction effects provide converging evidence that the clock gene and OXT/AVP systems are intertwined and contribute to human prosociality.

  2. Overexpression and enhanced specific activity of aldoketo reductases (AKR1B1 & AKR1B10) in human breast cancers.

    Science.gov (United States)

    Reddy, K Ashok; Kumar, P Uday; Srinivasulu, M; Triveni, B; Sharada, K; Ismail, Ayesha; Reddy, G Bhanuprakash

    2017-02-01

    The incidence of breast cancer in India is on the rise and is rapidly becoming the primary cancer in Indian women. The aldoketo reductase (AKR) family has more than 190 proteins including aldose reductase (AKR1B1) and aldose reductase like protein (AKR1B10). Apart from liver cancer, the status of AKR1B1 and AKR1B10 with respect to their expression and activity has not been reported in other human cancers. We studied the specific activity and expression of AKR1B1 and AKR1B10 in breast non tumor and tumor tissues and in the blood. Fresh post-surgical breast cancer and non-cancer tissues and blood were collected from the subjects who were admitted for surgical therapy. Malignant, benign and pre-surgical chemotherapy samples were evaluated by histopathology scoring. Expression of AKR1B1 and AKR1B10 was carried out by immunoblotting and immunohistochemistry (IHC) while specific activity was determined spectrophotometrically. The specific activity of AKR1B1 was significantly higher in red blood cells (RBC) in all three grades of primary surgical and post-chemotherapy samples. Specific activity of both AKR1B1 and AKR1B10 increased in tumor samples compared to their corresponding non tumor samples (primary surgical and post-chemotherapy). Immunoblotting and IHC data also indicated overexpression of AKR1B1 in all grades of tumors compared to their corresponding non tumor samples. There was no change in the specific activity of AKR1B1 in benign samples compared to all grades of tumor and non-tumors.

  3. Genetic variation of Cytochrome P450 1B1 (CYP1B1) and risk of breast cancer among Polish women.

    Science.gov (United States)

    Gaudet, Mia M; Chanock, Stephen; Lissowska, Jolanta; Berndt, Sonja I; Yang, Xiaohong Rose; Peplonska, Beata; Brinton, Louise A; Welch, Robert; Yeager, Meredith; Bardin-Mikolajczak, Alicja; Sherman, Mark E; Sutter, Thomas R; Garcia-Closas, Montserrat

    2006-08-01

    Four single nucleotide polymorphisms (SNPs) in CYP1B1 (Ex2 + 143 C > G, Ex2 + 356 G > T, Ex3 + 251 G > C, Ex3 + 315 A > G) cause amino acid changes (R48G, A119S, L432V and N453S, respectively) and are associated with increased formation of catechol estrogens; however, epidemiologic evidence only weakly supports an association between these variants and breast cancer risk. Because genetic variability conferring increased susceptibility could exist beyond these putative functional variants, we comprehensively examined the common genetic variability within CYP1B1. A total of eight haplotype-tagging (ht)SNPs (including Ex3 + 315 A > G), in addition to two putatively functional SNPs (Ex2 + 143 C > G and Ex3 + 251 G > C), were selected and genotyped in a large case-control study of Polish women (1995 cases and 2296 controls). Haplotypes were estimated using the expectation-maximization algorithm, and overall differences in the haplotype distribution between cases and controls were assessed using a global score test. We also evaluated levels of tumor CYP1B1 protein expression in a subset of 841 cases by immunohistochemistry, and their association with genetic variants. In the Polish population, we observed two linkage disequilibrium (LD)-defined blocks. Neither haplotypes (global P-value of 0.99 and 0.67 for each block of LD, respectively), nor individual SNPs (including three putatively functional SNPs) were associated with breast cancer risk. CYP1B1 was expressed in most tumor tissues (98%), and the level of expression was not related to the studied genetic variants. We found little evidence for modification of the estimated effect of haplotypes or individual SNPs by age, family history of breast cancer, or tumor hormone receptor status. The present study provides strong evidence against the existence of a substantial overall association between common genetic variation in CYP1B1 and breast cancer risk.

  4. MAN1B1 deficiency: an unexpected CDG-II.

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    Daisy Rymen

    Full Text Available Congenital disorders of glycosylation (CDG are a group of rare metabolic diseases, due to impaired protein and lipid glycosylation. In the present study, exome sequencing was used to identify MAN1B1 as the culprit gene in an unsolved CDG-II patient. Subsequently, 6 additional cases with MAN1B1-CDG were found. All individuals presented slight facial dysmorphism, psychomotor retardation and truncal obesity. Generally, MAN1B1 is believed to be an ER resident alpha-1,2-mannosidase acting as a key factor in glycoprotein quality control by targeting misfolded proteins for ER-associated degradation (ERAD. However, recent studies indicated a Golgi localization of the endogenous MAN1B1, suggesting a more complex role for MAN1B1 in quality control. We were able to confirm that MAN1B1 is indeed localized to the Golgi complex instead of the ER. Furthermore, we observed an altered Golgi morphology in all patients' cells, with marked dilatation and fragmentation. We hypothesize that part of the phenotype is associated to this Golgi disruption. In conclusion, we linked mutations in MAN1B1 to a Golgi glycosylation disorder. Additionally, our results support the recent findings on MAN1B1 localization. However, more work is needed to pinpoint the exact function of MAN1B1 in glycoprotein quality control, and to understand the pathophysiology of its deficiency.

  5. Role of nitric oxide in control of prolactin release by the adenohypophysis.

    Science.gov (United States)

    Duvilanski, B H; Zambruno, C; Seilicovich, A; Pisera, D; Lasaga, M; Diaz, M C; Belova, N; Rettori, V; McCann, S M

    1995-01-01

    Nitric oxide synthase-containing cells were visualized in the anterior pituitary gland by immunocytochemistry. Consequently, we began an evaluation of the possible role of NO in the control of anterior pituitary function. Prolactin is normally under inhibitory hypothalamic control, and in vitro the gland secretes large quantities of the hormone. When hemipituitaries were incubated for 30 min in the presence of sodium nitroprusside, a releaser of NO, prolactin release was inhibited. This suppression was completely blocked by the scavenger of NO, hemoglobin. Analogs of arginine, such as NG-monomethyl-L-arginine (NMMA, where NG is the terminal guanidino nitrogen) and nitroarginine methyl ester, inhibit NO synthase. Incubation of hemipituitaries with either of these compounds significantly increased prolactin release. Since in other tissues most of the actions of NO are mediated by activation of soluble guanylate cyclase with the formation of cyclic GMP, we evaluated the effects of cyclic GMP on prolactin release. Cyclic GMP (10 mM) produced an approximately 40% reduction in prolactin release. Prolactin release in vivo and in vitro can be stimulated by several peptides, which include vasoactive intestinal polypeptide and substance P. Consequently, we evaluated the possible role of NO in these stimulations by incubating the glands in the presence of either of these peptides alone or in combination with NMMA. In the case of vasoactive intestinal polypeptide, the significant stimulation of prolactin release was augmented by NMMA to give an additive effect. In the case of substance P, there was a smaller but significant release of prolactin that was not significantly augmented by NMMA. We conclude that NO has little effect on the stimulatory action of these two peptides on prolactin release. Dopamine (0.1 microM), an inhibitor of prolactin release, reduced prolactin release, and this inhibitory action was significantly blocked by either hemoglobin (20 micrograms/ml) or

  6. 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.

  7. Use of antiserum to neurotensin reveals a physiological role for the peptide in rat prolactin release.

    Science.gov (United States)

    Vijayan, E; Carraway, R; Leeman, S E; McCann, S M

    1988-01-01

    Previous studies have indicated that the brain peptide neurotensin can stimulate prolactin release by direct action on the pituitary gland, whereas its action within the hypothalamus is inhibitory. The inhibitory action is mediated by the release of dopamine into the hypophyseal portal veins, which deliver the neurotransmitter to the anterior pituitary gland to inhibit prolactin release. Our experiments were done to evaluate the physiologic significance of these neurotensin actions by injecting the globulin fraction of highly specific neurotensin antiserum either intravenously or intraventricularly. Injection into the third ventricle of either 1 or 3 microliter of neurotensin antiserum significantly increased plasma prolactin concentrations in (i) ovariectomized and (ii) ovariectomized estrogen- and progesterone-primed rats within 1 hr of injection. The response was more pronounced in the ovariectomized than in the ovariectomized estrogen- and progesterone-treated animals and was dose related. Intraventricular injection of these doses of neurotensin antiserum also evoked elevations in plasma prolactin in intact males, which were significant but smaller in magnitude than those seen in female rats. To evaluate the effect of the antiserum on the pituitary directly, the antiserum was injected intravenously at a dose of 40 microliter, which was sufficient to block the blood pressure-lowering effect of neurotensin. After the intravenous injection of antiserum, a highly significant suppression of plasma prolactin occurred, detectable when first measured at 1 hr after injection in both ovariectomized and ovariectomized estrogen- and progesterone-treated animals; however, the intravenous injection of antiserum had no significant effect on the prolactin release in males. These data indicate the physiological significance of the hypothalamic inhibitory actions of neurotensin on prolactin release, which are probably mediated by its stimulation of dopamine release that in turn

  8. 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.

  9. Aldo-Keto Reductases 1B in Endocrinology and Metabolism.

    Science.gov (United States)

    Pastel, Emilie; Pointud, Jean-Christophe; Volat, Fanny; Martinez, Antoine; Lefrançois-Martinez, Anne-Marie

    2012-01-01

    The aldose reductase (AR; human AKR1B1/mouse Akr1b3) has been the focus of many research because of its role in diabetic complications. The starting point of these alterations is the massive entry of glucose in polyol pathway where it is converted into sorbitol by this enzyme. However, the issue of AR function in non-diabetic condition remains unresolved. AR-like enzymes (AKR1B10, Akr1b7, and Akr1b8) are highly related isoforms often co-expressed with bona fide AR, making functional analysis of one or the other isoform a challenging task. AKR1B/Akr1b members share at least 65% protein identity and the general ability to reduce many redundant substrates such as aldehydes provided from lipid peroxidation, steroids and their by-products, and xenobiotics in vitro. Based on these properties, AKR1B/Akr1b are generally considered as detoxifying enzymes. Considering that divergences should be more informative than similarities to help understanding their physiological functions, we chose to review specific hallmarks of each human/mouse isoforms by focusing on tissue distribution and specific mechanisms of gene regulation. Indeed, although the AR shows ubiquitous expression, AR-like proteins exhibit tissue-specific patterns of expression. We focused on three organs where certain isoforms are enriched, the adrenal gland, enterohepatic, and adipose tissues and tried to connect recent enzymatic and regulation data with endocrine and metabolic functions of these organs. We presented recent mouse models showing unsuspected physiological functions in the regulation of glucido-lipidic metabolism and adipose tissue homeostasis. Beyond the widely accepted idea that AKR1B/Akr1b are detoxification enzymes, these recent reports provide growing evidences that they are able to modify or generate signal molecules. This conceptually shifts this class of enzymes from unenviable status of scavenger to upper class of messengers.

  10. Gonadotropin-releasing hormone stimulates prolactin release from lactotrophs in photoperiodic species through a gonadotropin-independent mechanism.

    Science.gov (United States)

    Henderson, Helen L; Hodson, David J; Gregory, Susan J; Townsend, Julie; Tortonese, Domingo J

    2008-02-01

    Previous studies have provided evidence for a paracrine interaction between pituitary gonadotrophs and lactotrophs. Here, we show that GnRH is able to stimulate prolactin (PRL) release in ovine primary pituitary cultures. This effect was observed during the breeding season (BS), but not during the nonbreeding season (NBS), and was abolished by the application of bromocriptine, a specific dopamine agonist. Interestingly, GnRH gained the ability to stimulate PRL release in NBS cultures following treatment with bromocriptine. In contrast, thyrotropin-releasing hormone, a potent secretagogue of PRL, stimulated PRL release during both the BS and NBS and significantly enhanced the PRL response to GnRH during the BS. These results provide evidence for a photoperiodically modulated functional interaction between the GnRH/gonadotropic and prolactin axes in the pituitary gland of a short day breeder. Moreover, the stimulation of PRL release by GnRH was shown not to be mediated by the gonadotropins, since immunocytochemical, Western blotting, and PCR studies failed to detect pituitary LH or FSH receptor protein and mRNA expressions. Similarly, no gonadotropin receptor expression was observed in the pituitary gland of the horse, a long day breeder. In contrast, S100 protein, a marker of folliculostellate cells, which are known to participate in paracrine mechanisms within this tissue, was detected throughout the pituitaries of both these seasonal breeders. Therefore, an alternative gonadotroph secretory product, a direct effect of GnRH on the lactotroph, or another cell type, such as the folliculostellate cell, may be involved in the PRL response to GnRH in these species.

  11. Aldo-Keto Reductases 1B in Adrenal Cortex Physiology.

    Science.gov (United States)

    Pastel, Emilie; Pointud, Jean-Christophe; Martinez, Antoine; Lefrançois-Martinez, A Marie

    2016-01-01

    Aldose reductase (AKR1B) proteins are monomeric enzymes, belonging to the aldo-keto reductase (AKR) superfamily. They perform oxidoreduction of carbonyl groups from a wide variety of substrates, such as aliphatic and aromatic aldehydes or ketones. Due to the involvement of human aldose reductases in pathologies, such as diabetic complications and cancer, AKR1B subgroup enzymatic properties have been extensively characterized. However, the issue of AKR1B function in non-pathologic conditions remains poorly resolved. Adrenal activities generated large amount of harmful aldehydes from lipid peroxidation and steroidogenesis, including 4-hydroxynonenal (4-HNE) and isocaproaldehyde (4-methylpentanal), which can both be reduced by AKR1B proteins. More recently, some AKR1B isoforms have been shown to be endowed with prostaglandin F synthase (PGFS) activity, suggesting that, in addition to possible scavenger function, they could instigate paracrine signals. Interestingly, the adrenal gland is one of the major sites for human and murine AKR1B expression, suggesting that their detoxifying/signaling activity could be specifically required for the correct handling of adrenal function. Moreover, chronic effects of ACTH result in a coordinated regulation of genes encoding the steroidogenic enzymes and some AKR1B isoforms. This review presents the molecular mechanisms accounting for the adrenal-specific expression of some AKR1B genes. Using data from recent mouse genetic models, we will try to connect their enzymatic properties and regulation with adrenal functions.

  12. 18 CFR 1b.20 - Request for confidential treatment.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Request for confidential treatment. 1b.20 Section 1b.20 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... disclosure requirements of the Freedom of Information Act (5 U.S.C. 552), is information referred to in 18...

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

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    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.

  14. CYP1B1 and hormone-induced cancer.

    Science.gov (United States)

    Gajjar, Ketan; Martin-Hirsch, Pierre L; Martin, Francis L

    2012-11-01

    Cancers in hormone-responsive tissues (e.g., breast, ovary, endometrium, prostate) occur at high incidence rates worldwide. However, their genetic basis remains poorly understood. Studies to date suggest that endogenous/exogenous oestrogen and environmental carcinogens may play a role in development and/or progression of hormone-induced cancers via oxidative oestrogen metabolism. Cytochrome P450 1B1 is a key enzyme in its oestrogen metabolism pathway, giving rise to hydroxylation and conjugation. Although CYP1B1 is expressed in many cancers, particularly high levels of expression are observed in oestrogen-mediated disease. CYP1B1 is more readily found in tumour tissue compared to normal. Given the role of CYP1B1 in pro-carcinogen and oestrogen metabolism, polymorphisms in CYP1B1 could result in modifications in its enzyme activity and subsequently lead to hormone-mediated carcinogenesis. CYP1B1 may also be involved in progression of the disease by altering the tissue response to hormones and clinical response to chemotherapy. The exact mechanism behind these events is complex and unclear. Only a few functional single nucleotide polymorphisms of CYP1B1 are known to result in amino acid substitutions and have been extensively investigated. Studies examining the contribution of different CYP1B1 alleles to hormone-mediated cancer risks are inconsistent. The main focus of this review is to appraise the available studies linking the pathogenesis of the hormone-induced cancers to various CYP1B1 polymorphisms. Additionally, we explore the role of a neuronal protein, γ-synuclein, in CYP1B1-mediated pathogenesis.

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

    Science.gov (United States)

    Treadwell, Edward L; Wiley, Kenneth; Word, Beverly; Melchior, William; Tolleson, William H; Gopee, Neera; Hammons, George; Lyn-Cook, Beverly D

    2015-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Expression of protein-tyrosine phosphatase 1B and insulin receptor substrate 2 in the skeletal muscle of rats with insulin resistance induced by high-fat diet%高脂饮食诱导肥胖模型大鼠骨骼肌组织蛋白酪氨酸磷酸酯酶1B和胰岛素受体底物2的表达

    Institute of Scientific and Technical Information of China (English)

    赵慧; 于苏国; 王令令; 赵艳敏

    2012-01-01

    背景:外周组织的胰岛素抵抗是2型糖尿病的主要病因.目的:观察高脂饮食诱导的肥胖大鼠骨骼肌中蛋白酪氨酸磷酸酯酶1B和胰岛素受体底物2的表达.方法:将20只SD大鼠随机等分为对照组和高脂组,分别给予常规饲料和高脂饲料喂养12周.结果和结论:与对照组相比,高脂组大鼠胰岛素敏感指数显著降低(P < 0.01),大鼠葡萄糖耐量受损,胰岛素释放试验提示葡萄糖刺激的胰岛素第一时相分泌受损,骨骼肌组织中蛋白酪氨酸磷酸酯酶1B蛋白表达水平明显增加(P < 0.01),骨骼肌中胰岛素诱导的胰岛素受体底物2磷酸化程度降低(P < 0.01).提示高脂饮食诱导的肥胖大鼠骨骼肌中蛋白酪氨酸磷酸酯酶1B蛋白表达量升高,使胰岛素诱导的胰岛素受体底物2磷酸化程度降低,可能是肥胖导致胰岛素抵抗的机制之一.%BACKGROUND: Insulin resistance in the peripheral tissue is a major cause of type 2 diabetes mellitus.OBJECTIVE: To observe the expression of protein tyrosine phosphatase 1B (PTP-1B) and insulin receptor substrate 2 (IRS-2) inthe skeletal muscle of rats with insulin resistance induced by high-fat diet.METHODS: Twenty SD rats were randomly divided into normal control group with 10 rats and high-fat diet group with 10 rats. Ratsin the two groups were fed with normal diet and high-fat diet for 12 weeks, respectively.RESULTS AND CONCLUSION: The insulin sensitive index was significantly decreased in the high-fat diet rats compared with thenormal rats (P < 0.01). In obese rats, glucose tolerance and the acute first-phase insulin secretory response to glucose wereimpaired. The protein level of PTP-1 B in the skeletal muscle of obese rats was significantly increased compared with the controlgroup (P< 0.01). Insulin-stimulated IRS-2 phosphorylation in the skeletal muscle was reduced in the obese rats (P< 0.01). Theseindicate that the increased PTP-1 B level and the reduced insulin-stimulated IRS-2

  18. Prolactin (PRL) in adipose tissue: regulation and functions.

    Science.gov (United States)

    Ben-Jonathan, Nira; Hugo, Eric

    2015-01-01

    New information concerning the effects of prolactin (PRL) on metabolic processes warrants reevaluation of its overall metabolic actions. PRL affects metabolic homeostasis by regulating key enzymes and transporters associated with glucose and lipid metabolism in several target organs. In the lactating mammary gland, PRL increases the production of milk proteins, lactose, and lipids. In adipose tissue, PRL generally suppresses lipid storage and adipokine release and affect adipogenesis. A specific case is made for PRL in the human breast and adipose tissues, where it acts as a circulating hormone and an autocrine/paracrine factor. Although its overall effects on body composition are both modest and species-specific, PRL may be involved in the manifestation of insulin resistance.

  19. Role of Estradiol in the Regulation of Prolactin Secretion During Late Pregnancy.

    Science.gov (United States)

    Villegas-Gabutti, Carlos; Pennacchio, Gisela E; Jahn, Graciela A; Soaje, Marta

    2016-12-01

    Estrogen action is necessary for evidencing the stimulatory action of mifepristone and naloxone on prolactin (PRL) secretion during late pregnancy. Our aim is to determine the mechanism mediating this facilitator action of estrogens. To investigate the hypothalamic mechanisms involved in estrogen actions in PRL secretion at the end of pregnancy, we measured the effect of pretreatment with the estrogen antagonist tamoxifen on the expression of tyrosine hydroxylase (TH), hormone receptors (ERα and β, PRs, PRLR(long)), and μ- and κ- opioid receptors (ORs) at mRNA (by semiquantitative RT-PCR) and protein (by western blot for TH, PRLR(long), ERα, PRs, μ- and ORs) levels in extracts of medial basal hypothalamus (MBH) and serum PRL, E2 and P4 levels (by RIA) in mifepristone- and naloxone-treated rats. Tamoxifen administration partially prevented PRL release induced by the combined treatment. TH expression diminished and ERα expression increased in mifepristone-treated rats at mRNA and protein levels and tamoxifen partially prevented these changes with no effect on PRs expression. Mifepristone increased PRLR(long) mRNA levels; this increase was blocked by tamoxifen. Combined tamoxifen and mifepristone treatment decreased μ- and k-ORs mRNA but not protein levels. In conclusion, E2 induces neuroadaptive mechanisms necessary to facilitate PRL release preceding delivery. Acting through ERα, E2 modulates hypothalamic dopaminergic neurons activity, regulating TH, μ- and κ-ORs and PRLR(long) expression, and is necessary for evidencing the effects of P4 withdrawal. Its presence on days 14 and 15 of pregnancy is crucial to facilitate the opioid system modulation of PRL secretion at the end of pregnancy in the rat.

  20. Postprandial prolactin suppression appears absent in antipsychotic-treated male patients

    DEFF Research Database (Denmark)

    Coello, Klara; Broberg, Brian Villumsen; Bak, Nikolaj;

    2015-01-01

    INTRODUCTION: Hyperprolactinemia is a common side-effect of antipsychotic treatment. Antipsychotics and hyperprolactinemia are both considered risk factors of metabolic disturbances and diabetes. Investigations on prolactin response to meal ingestion in antipsychotic-treated patients are missing...

  1. Predominant role of the 9-hydroxy metabolite of risperidone in elevating blood prolactin levels

    NARCIS (Netherlands)

    Knegtering, R; Baselmans, P; Castelein, S; Bosker, F; Bruggeman, R; van den Bosch, RJ

    2005-01-01

    Objective: The atypical antipsychotic risperidone significantly raises plasma prolactin levels in patients, but clozapine, olanzapine, and quetiapine do not. The differences in neuroendocrine response may be connected with the metabolism of the medications. The authors examined the contributory role

  2. PREPUBERTAL EXPOSURES TO COMPOUNDS THAT INCREASE PROLACTIN SECRETION IN THE MALE RAT: EFFECTS ON ADULT PROSTATE

    Science.gov (United States)

    Prepubertal exposure to compounds that increase prolactin secretion in the male rat: effects on the adult prostate.Stoker TE, Robinette CL, Britt BH, Laws SC, Cooper RL.Endocrinology Branch, Reproductive Toxicology Division, National Health and Environmental Effec...

  3. SERUM PROLACTIN ASSAY: AN IMPORTANT SCREENING METHOD IN PRIMARY AND SECONDARY INFERTILITY IN FEMALE

    Directory of Open Access Journals (Sweden)

    Sanjaya

    2016-02-01

    Full Text Available BACKGROUND Infertility represents a common condition nowadays with important medical, economic and psychological implications. Traditionally, measurement of Prolactin has been considered an important component of infertility workup in women. AIMS The study was designed to evaluate the serum prolactin assay in patients with primary and secondary infertility. METHOD In this retrospective case control study, we investigated one fifty (150 infertile women in the age range of 20-40 years attending Department of Obs. and Gynae. MLB Medical College, Jhansi, for infertility treatment. Fifty (50 fertile women with similar age range were selected as controls. The association between infertility and levels of serum Prolactin was reviewed. RESULTS Hyperprolactinemia was depicted in 24.66% infertile women. Prevalence of primary infertility was 68%, while that of secondary infertility cases was 32%. There was a correlation between Prolactin levels in infertile subjects (p <0.05. CONCLUSION There was higher prevalence of hyperprolactinemia in infertile patients

  4. CYP1B1: a unique gene with unique characteristics.

    Science.gov (United States)

    Faiq, Muneeb A; Dada, Rima; Sharma, Reetika; Saluja, Daman; Dada, Tanuj

    2014-01-01

    CYP1B1, a recently described dioxin inducible oxidoreductase, is a member of the cytochrome P450 superfamily involved in the metabolism of estradiol, retinol, benzo[a]pyrene, tamoxifen, melatonin, sterols etc. It plays important roles in numerous physiological processes and is expressed at mRNA level in many tissues and anatomical compartments. CYP1B1 has been implicated in scores of disorders. Analyses of the recent studies suggest that CYP1B1 can serve as a universal/ideal cancer marker and a candidate gene for predictive diagnosis. There is plethora of literature available about certain aspects of CYP1B1 that have not been interpreted, discussed and philosophized upon. The present analysis examines CYP1B1 as a peculiar gene with certain distinctive characteristics like the uniqueness in its chromosomal location, gene structure and organization, involvement in developmentally important disorders, tissue specific, not only expression, but splicing, potential as a universal cancer marker due to its involvement in key aspects of cellular metabolism, use in diagnosis and predictive diagnosis of various diseases and the importance and function of CYP1B1 mRNA in addition to the regular translation. Also CYP1B1 is very difficult to express in heterologous expression systems, thereby, halting its functional studies. Here we review and analyze these exceptional and startling characteristics of CYP1B1 with inputs from our own experiences in order to get a better insight into its molecular biology in health and disease. This may help to further understand the etiopathomechanistic aspects of CYP1B1 mediated diseases paving way for better research strategies and improved clinical management.

  5. 6β-hydroxytestosterone, a cytochrome P450 1B1 metabolite of testosterone, contributes to angiotensin II-induced hypertension and its pathogenesis in male mice.

    Science.gov (United States)

    Pingili, Ajeeth K; Kara, Mehmet; Khan, Nayaab S; Estes, Anne M; Lin, Zongtao; Li, Wei; Gonzalez, Frank J; Malik, Kafait U

    2015-06-01

    Previously, we showed that Cyp1b1 gene disruption minimizes angiotensin II-induced hypertension and associated pathophysiological changes in male mice. This study was conducted to test the hypothesis that cytochrome P450 1B1-generated metabolites of testosterone, 6β-hydroxytestosterone and 16α-hydroxytestosterone, contribute to angiotensin II-induced hypertension and its pathogenesis. Angiotensin II infusion for 2 weeks increased cardiac cytochrome P450 1B1 activity and plasma levels of 6β-hydroxytestosterone, but not 16α-hydroxytestosterone, in Cyp1b1(+/+) mice without altering Cyp1b1 gene expression; these effects of angiotensin II were not observed in Cyp1b1(-/-) mice. Angiotensin II-induced increase in systolic blood pressure and associated cardiac hypertrophy, and fibrosis, measured by intracardiac accumulation of α-smooth muscle actin, collagen, and transforming growth factor-β, and increased nicotinamide adenine dinucleotide phosphate oxidase activity and production of reactive oxygen species; these changes were minimized in Cyp1b1(-/-) or castrated Cyp1b1(+/+) mice, and restored by treatment with 6β-hydroxytestoterone. In Cyp1b1(+/+) mice, 6β-hydroxytestosterone did not alter the angiotensin II-induced increase in systolic blood pressure; the basal systolic blood pressure was also not affected by this agent in either genotype. Angiotensin II or castration did not alter cardiac, angiotensin II type 1 receptor, angiotensin-converting enzyme, Mas receptor, or androgen receptor mRNA levels in Cyp1b1(+/+) or in Cyp1b1(-/-) mice. These data suggest that the testosterone metabolite, 6β-hydroxytestosterone, contributes to angiotensin II-induced hypertension and associated cardiac pathogenesis in male mice, most probably by acting as a permissive factor. Moreover, cytochrome P450 1B1 could serve as a novel target for developing agents for treating renin-angiotensin and testosterone-dependent hypertension and associated pathogenesis in males.

  6. PTP1B deficiency increases glucose uptake in neonatal hepatocytes: involvement of IRA/GLUT2 complexes.

    Science.gov (United States)

    González-Rodriguez, Agueda; Nevado, Carmen; Escrivá, Fernando; Sesti, Giorgio; Rondinone, Cristina M; Benito, Manuel; Valverde, Angela M

    2008-08-01

    The contribution of the liver to glucose utilization is essential to maintain glucose homeostasis. Previous data from protein tyrosine phosphatase (PTP) 1B-deficient mice demonstrated that the liver is a major site for PTP1B action in the periphery. In this study, we have investigated the consequences of PTP1B deficiency in glucose uptake in hepatocytes from neonatal and adult mice. The lack of PTP1B increased basal glucose uptake in hepatocytes from neonatal (3-5 days old) but not adult (10-12 wk old) mice. This occurs without changes in hexokinase, glucokinase, and glucose 6-phosphatase enzymatic activities. By contrast, the glucose transporter GLUT2 was upregulated at the protein level in neonatal hepatocytes and livers from PTP1B-deficient neonates. These results were accompanied by a significant increase in the net free intrahepatic glucose levels in the livers of PTP1B(-/-) neonates. The association between GLUT2 and insulin receptor (IR) A isoform was increased in PTP1B(-/-) neonatal hepatocytes compared with the wild-type. Indeed, PTP1B deficiency in neonatal hepatocytes shifted the ratio of isoforms A and B of the IR by increasing the amount of IRA and decreasing IRB. Moreover, overexpression of IRA in PTP1B(-/-) neonatal hepatocytes increased the amount of IRA/GLUT2 complexes. Conversely, hepatocytes from adult mice only expressed IRB. Since IRA plays a direct role in the regulation of glucose uptake in neonatal hepatocytes through its specific association with GLUT2, we propose the increase in IRA/GLUT2 complexes due to PTP1B deficiency as the molecular mechanism of the increased glucose uptake in the neonatal stage.

  7. Establishment of Reference Interval of Serum Prolactin in an Indian Population

    OpenAIRE

    Lahiri, Kapil Deb; Baruah, Mriganka; Ghosh, Joya; Sengupta, Soumendyu

    2014-01-01

    Background: Reference data on serum prolactin levels based on a representative Indian sample are still lacking. The western normative laboratory values used for clinical diagnosis may not be applicable to Indian population. The objective of the study was to measure the serum prolactin levels in healthy Indian male and female in order to establish reference interval and to compare with the available reference intervals. It is a cross- sectional study done in West Bengal, India.

  8. Effects of Neonatal Exposure to Estradiol on Prolactin Secretion and Activity of the Tubero-lnfundibular Dopamine System in Young Adulthood: Comparison with Neonatal Prolactin Deficiency*.

    Science.gov (United States)

    Crowley, W R; Shah, G V; Watanobe, H; Grosvenor, C E

    1990-02-01

    Abstract Previous results from this laboratory indicate that female rats who consume milk deficient in prolactin (PRL) during the neonatal period subsequently display hyperprolactinemia, associated with decreased activity in the tubero-infundibular dopamine (DA) system and decreased lactotrope responsiveness to DA receptor stimulation. The present studies tested whether these neuroendocrine consequences of neonatal PRL deficiency can be mimicked by exposure of neonatal rats to estradiol. Female rats were injected sc with 1 mUg estradiol benzoate or oil vehicle on postpartum Days one to 3, while in other experiments, females were made neonatally deficient in PRL through treatment of their mothers with the DA agonist bromocriptine, a treatment that reduces the levels of PRL in milk. Females treated neonatally with estradiol benzoate, as well as offspring of the bromocriptine-treated mothers, displayed hyperprolactinemia as young adults, as compared to their respective vehicle-matched controls, and in both cases, this was abolished by ovariectomy, indicating dependence upon ovarian secretions. As reported previously in neonatal PRL-deficient females, neonatal estradiol benzoate-treated animals also exhibited reduced steady state levels and decreased turnover rates of DA in the median eminence when 35 days of age. DA levels and turnover rates in this region were still significantly reduced on postpartum Day 60. The DA agonist bromocriptine suppressed PRL release to a similar extent in cultured anterior pituitary cells from neonatal estrogen-treated and control rats, suggesting normal responsiveness of DA receptors on lactotrope cells in both groups. The present results confirm the ability of estradiol treatment or induction of a PRL deficiency during the early neonatal period to induce subsequent hyperprolactinemia in female rats, and further indicate that the hyperprolactinemic conditions resulting from either neonatal manipulation are dependent on the ovary and are

  9. Hepatic protein tyrosine phosphatase 1B (PTP1B) deficiency protects against obesity-induced endothelial dysfunction.

    Science.gov (United States)

    Agouni, Abdelali; Tual-Chalot, Simon; Chalopin, Matthieu; Duluc, Lucie; Mody, Nimesh; Martinez, M Carmen; Andriantsitohaina, Ramaroson; Delibegović, Mirela

    2014-12-15

    Growing evidence suggests that hepatic-insulin resistance is sufficient to promote progression to cardiovascular disease. We have shown previously that liver-specific protein-tyrosine-phosphatase 1B (PTP1B) deficiency improves hepatic-insulin sensitivity and whole-body glucose homeostasis. The aim of this study was to investigate the impact of liver-specific PTP1B-deficiency (L-PTP1B-/-) on cardiac and peripheral vascular function, with special emphasis on endothelial function in the context of high-fat diet (HFD)-induced obesity. L-PTP1B-/- mice exhibited an improved glucose and lipid homeostasis and increased insulin sensitivity, without changes in body weight. HFD-feeding increased systolic blood pressure (BP) in both L-PTP1B-/- and control littermates; however, this was significantly lower in L-PTP1B-/- mice. HFD-feeding increased diastolic BP in control mice only, whilst the L-PTP1B-/- mice were completely protected. The analysis of the function of the left ventricle (LV) revealed that HFD-feeding decreased LV fractional shortening in control animals, which was not observed in L-PTP1B-/- mice. Importantly, HFD feeding significantly impaired endothelium-dependent vasorelaxation in response to acetylcholine in aortas from control mice, whilst L-PTP1B-/- mice were fully protected. This was associated with alterations in eNOS phosphorylation. Selective inhibition of COX-2, using NS-398, decreased the contractile response in response to serotonin (5-HT) only in vessels from control mice. HFD-fed control mice released enhanced levels of prostaglandin E, a vasoconstrictor metabolite; whilst both chow- and HFD-fed L-PTP1B-/- mice released higher levels of prostacylin, a vasorelaxant metabolite. Our data indicate that hepatic-PTP1B inhibition protects against HFD-induced endothelial dysfunction, underscoring the potential of peripheral PTP1B inhibitors in reduction of obesity-associated cardiovascular risk in addition to its anti-diabetic effects.

  10. Identification and Characterization of Two Novel RNA Editing Sites in grin1b Transcripts of Embryonic Danio rerio

    Directory of Open Access Journals (Sweden)

    Pedro Pozo

    2012-01-01

    Full Text Available Discovering RNA editing sites in model organisms provides an insight into their adaptations in addition to finding potential sites for the regulation of neural activity and the basis of integrated models of metazoan editing with a variety of applications, including potential clinical treatments of neural dysregulation. The zebrafish, Danio rerio, is an important vertebrate model system. We focused on the grin1b gene of zebrafish due to its important function in the nervous tissue as a glutamate receptor. Using a comparative sequence-based approach, we located possible RNA editing events within the grin1b transcript. Surprisingly, sequence analysis also revealed a new editing site which was not predicted by the comparative approach. We here report the discovery of two novel RNA editing events in grin1b transcripts of embryonic zebrafish. The frequency of these editing events and their locations within the grin1b transcript are also described.

  11. A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk

    NARCIS (Netherlands)

    Bouatia-Naji, Nabila; Bonnefond, Amelie; Cavalcanti-Proenca, Christine; Sparso, Thomas; Holmkvist, Johan; Marchand, Marion; Delplanque, Jerome; Lobbens, Stephane; Rocheleau, Ghislain; Durand, Emmanuelle; De Graeve, Franck; Chevre, Jean-Claude; Borch-Johnsen, Knut; Hartikainen, Anna-Liisa; Ruokonen, Aimo; Tichet, Jean; Marre, Michel; Weill, Jacques; Heude, Barbara; Tauber, Maithe; Lemaire, Katleen; Schuit, Frans; Elliott, Paul; Jorgensen, Torben; Charpentier, Guillaume; Hadjadj, Samy; Cauchi, Stephane; Vaxillaire, Martine; Sladek, Robert; Visvikis-Siest, Sophie; Balkau, Beverley; Levy-Marchal, Claire; Pattou, Francois; Meyre, David; Blakemore, Alexandra I. F.; Jarvelin, Marjo-Riita; Walley, Andrew J.; Hansen, Torben; Dina, Christian; Pedersen, Oluf; Froguel, Philippe

    2009-01-01

    In genome-wide association (GWA) data from 2,151 nondiabetic French subjects, we identified rs1387153, near MTNR1B (which encodes the melatonin receptor 2 (MT2)), as a modulator of fasting plasma glucose (FPG; P = 1.3 x 10(-7)). In European populations, the rs1387153 T allele is associated with incr

  12. Regulation of prolactin secretion by hypothalamus in some cold blooded vertebrates.

    Science.gov (United States)

    Singh, S P; Singh, T P

    1980-07-01

    Effect of homoplastic hypothalamic extract (HHE) on the release of prolactin from the pituitary gland of three aquatic animals -- the fish, Clarias batrachus, the amphibian, Rana tigrina and the reptile, Natrix piscator was studied. Release of prolactin from the pituitary gland in the above animals was blocked within 4 hours by CG 603 (100 microgram/g body wt.) injection. Administration of HHE and perphenazine (15 microgram/g body wt.) in such animals resulted in significantly increased level of prolactin in the blood serum within one hour of treatment indicating an accelerated release of prolactin from the pituitary gland. Injection of cerebral cortical extract failed to induce such response in any of the specimens. From the findings of the present experimentation it is evident that the hypothalamus in C. batrachus, R. tigrina and N. piscator contained predominantly prolactin-release stimulatory factor (PRF) at the time of assessment. Probably in the aquatic poikilotherms where prolactin is not essential for their survival in hypophysectomized condition, hypothalamus contains PRF at least for some period in a year.

  13. Prolactin suppresses malonyl-CoA concentration in human adipose tissue.

    Science.gov (United States)

    Nilsson, L A; Roepstorff, C; Kiens, B; Billig, H; Ling, C

    2009-10-01

    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 as a consequence of suppressed malonyl-CoA concentration in parallel with decreased GLUT-4 expression. In the lactating woman, this regulation in adipose tissue may enhance the provision of nutrients for the infant instead of nutrients being stored in adipose tissue. In hyperprolactinemic individuals, a suppressed lipogenesis could contribute to an insulin resistant state with consequences for the health.

  14. Prolactin and estradiol serum levels in unmedicated male paranoid schizophrenia patients.

    Science.gov (United States)

    Segal, Michael; Avital, Avi; Berstein, Severina; Derevenski, Andrei; Sandbank, Sergio; Weizman, Abraham

    2007-03-30

    There is evidence for the involvement of the endocrine system in schizophrenia. This involment was widely investigated in female patients. In the current study, we examined prolactin and estradiol serum levels in hospitalized unmedicated men with first-episode and recurrent schizophrenia and then tested possible correlation with various subtypes of the disease. In addition, the estradiol and prolactin levels were compared with a healthy control group. The serum samples were assessed the morning following admission in fifty-seven schizophrenia male patients. There was a significant difference in prolactin serum levels between the paranoid and "nonparanoid" schizophrenia subgroups. However, no significant differences were found in estradiol serum levels between schizophrenia subtypes or between the patients and their healthy counterparts. Finally, a significant and positive correlation was found between the prolactin and estradiol levels in the paranoid subgroup alone. Thus, it appears that low estradiol levels are associated with low prolactin levels, alleged hyperdopaminergic tone and psychotic breakdown in paranoid schizophrenia. The results of the present study further support our previous report of the association between prolactin serum levels and the schizophrenia cluster subtypes, indicating a different dopaminergic activity for the various forms of the disease.

  15. Prolactin elevation with antipsychotic medications: mechanisms of action and clinical consequences.

    Science.gov (United States)

    Maguire, Gerald A

    2002-01-01

    Antipsychotic agents differ in efficacy and side effects such as movement disorders and prolactin elevation because of varying mechanisms of action. A revised nomenclature for antipsychotic agents, which categorizes the drugs according to efficacy, risk of movement disorders, and risk of prolactin elevation, is described. Prolactin elevation, a potential side effect of some antipsychotic medications, is underdiagnosed but can have serious short-term and long-term consequences. Short-term problems include menstrual irregularities, sexual dysfunction, and depression. Long-term problems related to prolactin elevation include decreased bone density and osteoporosis, relapse of psychosis because of poor compliance due to sexual dysfunction or depression, and perhaps cancer, although more research in this area is needed. Despite the serious nature of these effects, prolactin elevation is seldom detected because clinicians often fail to inquire about sexual function or other symptoms that signal that a patient's prolactin may be elevated. These are problems that patients may not bring up with clinicians unless they are asked. Therefore, when patients are taking antipsychotic medications, clinicians should regularly inquire about sexual dysfunction, depression, menstrual disturbances, galactorrhea, and gynecomastia.

  16. 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. ?? The American Ornithologists' Union, 2006. Printed in USA.

  17. A predictive algorithm for evaluating elevated serum prolactin in patients with a sellar mass.

    Science.gov (United States)

    Cheng, Jason S; Salinas, Ryan; Molinaro, Annette; Chang, Edward F; Kunwar, Sandeep; Blevins, Lewis; Aghi, Manish K

    2015-01-01

    Hyperprolactinemia occurs in patients with a prolactinoma and in those with a sellar mass compressing the pituitary stalk. Distinguishing these two diagnostic possibilities guides treatment with dopamine agonist therapy or surgical resection. We aimed to identify a simple, predictive algorithm to aid in the diagnosis of prolactinoma in patients with an elevated serum prolactin and a sellar mass. A case-control analysis of pathologically confirmed prolactinomas and non-endocrine secreting controls from the University of California, San Francisco was performed. From 2001 to 2011, this resulted in 177 patients with prolactinomas and 87 controls. Univariate and classification and regression tree (CART) analysis determined the significance of demographic variables, patient symptoms, laboratory values, and radiographic findings in distinguishing pathology. Additionally, a subset of patients with mildly elevated serum prolactin (25-125 ng/ml) was independently analyzed. Prolactinomas had a mean pre-operative prolactin of 858 ng/ml versus 17.57 ng/ml in controls (p10mm) compared to 74 (92.5%) of the controls (pprolactin (>41.5 ng/ml), age (prolactin (prolactin (>40 ng/ml) as key variables. These two factors correctly predicted 98.6% (69/70) of cases. Our model correctly classifies most patients with elevated serum prolactin and identifies those patients most amenable to surgical treatment.

  18. 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.

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

    Science.gov (United States)

    Hashemian, F; Shafigh, F; Roohi, E

    2016-01-01

    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.

  20. Prolactin secretion and ovarian function in cycling and non-cycling African female elephants (Loxodonta africana).

    Science.gov (United States)

    Yamamoto, Yuki; Yamamoto, Tatsuya; Watanabe, Gen; Yuto, Natsuki; Keio, Megumi; Narushima, Etsuo; Katayanagi, Masayuki; Nakao, Risa; Morikubo, Syu; Sakurai, Yuko; Kaneko, Mikako; Kaewmanee, Saroch; Taya, Kazuyoshi

    2010-07-01

    Reproduction of captive elephants in zoos has shown a low fecundity and requires improvement. One of the reasons for low fecundity is ovarian dysfunction in many female elephants. To investigate whether prolactin has a correlation with ovarian function in female elephants, the serum concentrations of prolactin, progesterone and estradiol-17beta in four African female elephants (one cycling female and three non-cycling female elephants) were measured. Cyclic patterns of prolactin and estradiol-17beta were observed in the cycling female elephant, which tended to be high during the follicular phase and low during the luteal phase. On the other hand, a cyclic pattern of prolactin was not observed in the non-cycling female elephants. One of the three non-cycling females (Mako) had developed breasts and showed significantly higher average levels of prolactin than the other female elephants. These results suggested that high concentrations of circulating estradiol-17beta during the follicular phase stimulated prolactin secretion. They also suggested that hyperprolactinemia in Mako was one of the causes of the developed mammary glands and ovarian dysfunction.

  1. Enzymes of the AKR1B and AKR1C subfamilies and uterine diseases

    Directory of Open Access Journals (Sweden)

    Tea eLanisnik Rizner

    2012-03-01

    Full Text Available Endometrial and cervical cancers, uterine myoma, and endometriosis are very common uterine diseases. Worldwide, more than 800,000 women are affected annually by gynecological cancers, as a result of which, more than 360,000 die. During their reproductive age, about 70% of women develop uterine myomas, 10% to 15% suffer from endometriosis, and 35% to 50% from infertility associated with endometriosis. Uterine diseases are associated with aberrant inflammatory responses and concomitant increased production of prostaglandins (PG. They are also related to decreased differentiation, due to low levels of protective progesterone and retinoic acid, and to enhanced proliferation, due to high local concentrations of estrogens. The pathogenesis of these diseases can thus be attributed to disturbed PG, estrogen and retinoid metabolism and actions. Five human members of the aldo-keto reductase 1B (AKR1B and 1C (AKR1C superfamilies, i.e., AKR1B1, AKR1B10, AKR1C1, AKR1C2 and AKR1C3, have roles in these processes and can thus be implicated in uterine diseases. AKR1B1 and AKR1C3 catalyze the formation of PGF2alpha which stimulates cell proliferation. AKR1C3 converts PGD2 to 9alpha,11beta-PGF2, and thus counteracts the formation of 15deoxy-PGJ2, which can activate pro-apoptotic peroxisome-proliferator-activated receptor beta. AKR1B10 catalyzes the reduction of retinal to retinol, and in thus lessens the formation of retinoic acid, with potential pro-differentiating actions. The AKR1C1-AKR1C3 enzymes also act as 17-keto- and 20-ketosteroid reductases to varying extents, and are implicated in increased estradiol and decreased progesterone levels. This review comprises a short introduction to uterine diseases, followed by an overview of the current literature on the AKR1B and AKR1C expression in the uterus and in uterine diseases. The potential implications of the AKR1B and AKR1C enzymes and their pathophysiologies are then discussed, followed by conclusions and

  2. TES/Aura L1B Spectra Limb V002

    Data.gov (United States)

    National Aeronautics and Space Administration — The L1B Limb granule consists of radiometrically calibrated spectra & associated NESR, observed at 0.025 cm-1 resolution for an entire Global Survey &...

  3. TES/Aura L1B Spectra Nadir V003

    Data.gov (United States)

    National Aeronautics and Space Administration — The L1B Nadir granule consists of radiometrically calibrated spectra & associated NESR, observed at 0.1 cm-1 resolution for an entire Global Survey &...

  4. TES/Aura L1B Spectra Nadir V004

    Data.gov (United States)

    National Aeronautics and Space Administration — The L1B Nadir granule consists of radiometrically calibrated spectra & associated NESR, observed at 0.1 cm-1 resolution for an entire Global Survey &...

  5. Aldo-keto reductases 1B in adrenal cortex physiology

    Directory of Open Access Journals (Sweden)

    Emilie PASTEL

    2016-07-01

    Full Text Available Aldose reductase proteins are cytosolic monomeric enzymes, belonging to the aldo-keto reductase (AKR superfamily. They perform oxidoreduction of carbonyl groups from a wide variety of substrates such as aliphatic and aromatic aldehydes or ketones. The Aldose reductase subgroup (AKR1B is one of the most characterized because of its involvement in human diseases such as diabetic complications resulting from the ability of its human archetype AKR1B1 to reduce glucose into sorbitol. However the issue of AKR1B function in non pathologic condition remains poorly resolved. Adrenal steroidogenesis is strongly associated with high production of endogenous harmful lipid aldehyde by-products including isocaproaldehyde (4-methylpentanal derived from cholesterol side chain cleavage (the first step of steroid synthesis and 4-hydroxynonenal (4- HNE that can both be reduced by AKR1B proteins. More recently, some AKR1B isoforms have been shown to be endowed with prostaglandin F synthase activity, suggesting that in addition to possible scavenger function, they could instigate paracrine signals. Interestingly, previous studies have established that the adrenal gland is one of the major site for human and murine AKR1B expression suggesting that their detoxifying/signaling activity could be specifically required for the correct handling of adrenal function. Moreover chronic effects of ACTH result in a coordinated regulation of genes encoding the steroidogenic enzymes and some AKR1B isoforms.This review presents the molecular mechanisms accounting for the adrenal specific expression of some AKR1B genes. Using data from recent mouse genetic models, we will try to connect their enzymatic properties and regulation with adrenal functions.

  6. CIAE Signs Contract on B1/B2 Project

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    CIAE signed Contract on Design,Commissioning and Technology Service for B1/B2 Project of Birine Reactor with CZEC in December,2015.The B1/B2 project which was won over by CZEC is PhaseⅠand PhaseⅡof an Algeria project which aimed to upgrade and rebuild Algeria Birine Nuclear Research Center.According to the contract with total fund amounting to 110million Yuan,CIAE will provide

  7. CYP1B1-mediated Pathobiology of Primary Congenital Glaucoma.

    Science.gov (United States)

    Faiq, Muneeb A; Dada, Rima; Qadri, Rizwana; Dada, Tanuj

    2015-01-01

    CYP1B1 is a dioxin-inducible enzyme belonging to the cytochrome P450 superfamily. It has been observed to be important in a variety of developmental processes including in utero development of ocular structures. Owing to its role in the developmental biology of eye, its dysfunction can lead to ocular developmental defects. This has been found to be true and CYP1B1 mutations have been observed in a majority of primary congenital glaucoma (PCG) patients from all over the globe. Primary congenital glaucoma is an irreversibly blinding childhood disorder (onset at birth or early infancy) typified by anomalous development of trabecular meshwork (TM). How CYP1B1 causes PCG is not known; however, some basic investigations have been reported. Understanding the CYP1B1 mediated etiopathomechanism of PCG is very important to identify targets for therapy and preventive management. In this perspective, we will make an effort to reconstruct the pathomechanism of PCG in the light of already reported information about the disease and the CYP1B1 gene. How to cite this article: Faiq MA, Dada R, Qadri R, Dada T. CYP1 B1-mediated Pathobiology of Primary Congenital Glaucoma. J Curr Glaucoma Pract 2015;9(3):77-80.

  8. PTP1B inhibitors from stems of Angelica keiskei (Ashitaba).

    Science.gov (United States)

    Li, Jin-Long; Gao, Li-Xin; Meng, Fan-Wang; Tang, Chun-Lan; Zhang, Ru-Jun; Li, Jing-Ya; Luo, Cheng; Li, Jia; Zhao, Wei-Min

    2015-01-01

    Three new chalcones, xanthoangelols K-M (1-3), together with 19 known compounds were isolated from the stems of Angelica keiskei Koidzumi, a well-known rejuvenated and anti-diabetic plant originated from Japan. The structures of compounds 1-3 were elucidated on the basis of spectroscopic data and Mosher's method. All compounds were evaluated for their inhibitory activity against protein tyrosine phosphatase 1B (PTP1B). Among them, six chalcones, xanthoangelol K (1), xanthoangelol (4), xanthoangelol F (5), 4-hydroxyderricin (6), xanthoangelol D (7), xanthoangelol E (8), and a coumarin, methoxsalen (17), showed strong PTP1B inhibitory effect with IC50 values of 0.82, 1.97, 1.67, 2.47, 3.97, 1.43, and 2.53μg/mL, respectively. A kinetic study revealed that compound 1 inhibited PTP1B with characteristics typical of a competitive inhibitor. Molecular docking simulations elucidated that ring B of 1 may anchor in a pocket of PTP1B and the molecule is stabilized by hydrogen bonds with Arg47, Asp48, and π-π interaction with Phe182 of PTP1B.

  9. Association of transcription factor gene LMX1B with autism.

    Directory of Open Access Journals (Sweden)

    Ismail Thanseem

    Full Text Available Multiple lines of evidence suggest a serotoninergic dysfunction in autism. The role of LMX1B in the development and maintenance of serotoninergic neurons is well known. In order to examine the role, if any, of LMX1B with autism pathophysiology, a trio-based SNP association study using 252 family samples from the AGRE was performed. Using pair-wise tagging method, 24 SNPs were selected from the HapMap data, based on their location and minor allele frequency. Two SNPs (rs10732392 and rs12336217 showed moderate association with autism with p values 0.018 and 0.022 respectively in transmission disequilibrium test. The haplotype AGCGTG also showed significant association (p = 0.008. Further, LMX1B mRNA expressions were studied in the postmortem brain tissues of autism subjects and healthy controls samples. LMX1B transcripts was found to be significantly lower in the anterior cingulate gyrus region of autism patients compared with controls (p = 0.049. Our study suggests a possible role of LMX1B in the pathophysiology of autism. Based on previous reports, it is likely to be mediated through a seretoninergic mechanism. This is the first report on the association of LMX1B with autism, though it should be viewed with some caution considering the modest associations we report.

  10. Association of transcription factor gene LMX1B with autism.

    Science.gov (United States)

    Thanseem, Ismail; Nakamura, Kazuhiko; Anitha, Ayyappan; Suda, Shiro; Yamada, Kazuo; Iwayama, Yoshimi; Toyota, Tomoko; Tsujii, Masatsugu; Iwata, Yasuhide; Suzuki, Katsuaki; Matsuzaki, Hideo; Iwata, Keiko; Sugiyama, Toshiro; Yoshikawa, Takeo; Mori, Norio

    2011-01-01

    Multiple lines of evidence suggest a serotoninergic dysfunction in autism. The role of LMX1B in the development and maintenance of serotoninergic neurons is well known. In order to examine the role, if any, of LMX1B with autism pathophysiology, a trio-based SNP association study using 252 family samples from the AGRE was performed. Using pair-wise tagging method, 24 SNPs were selected from the HapMap data, based on their location and minor allele frequency. Two SNPs (rs10732392 and rs12336217) showed moderate association with autism with p values 0.018 and 0.022 respectively in transmission disequilibrium test. The haplotype AGCGTG also showed significant association (p = 0.008). Further, LMX1B mRNA expressions were studied in the postmortem brain tissues of autism subjects and healthy controls samples. LMX1B transcripts was found to be significantly lower in the anterior cingulate gyrus region of autism patients compared with controls (p = 0.049). Our study suggests a possible role of LMX1B in the pathophysiology of autism. Based on previous reports, it is likely to be mediated through a seretoninergic mechanism. This is the first report on the association of LMX1B with autism, though it should be viewed with some caution considering the modest associations we report.

  11. Localization and significance of serotonin receptor 1B in the spiral ganglion in micee%5羟色胺1B受体在小鼠耳蜗螺旋神经元上的表达及意义

    Institute of Scientific and Technical Information of China (English)

    白云丹; 喻超; 唐玥玓

    2012-01-01

    目的 研究小鼠耳蜗螺旋神经元上5羟色胺(serotonin,5-HT)1B受体的表达并探讨其意义.方法 采用成熟昆明小鼠耳蜗石蜡切片,运用免疫组化技术检测耳蜗螺旋神经元上5羟色胺1B受体的表达.结果 实验组小鼠耳蜗螺旋神经元胞浆内显示阳性表达信号,阴性对照组未发现阳性信号.结论 5羟色胺1B受体存在于听觉传导通路的第一级神经元,支持5羟色胺作为其递质,对神经兴奋性起着重要的调节作用.%Objective To investigate the expression of serotonin (5-HT) receptor lB in spiral ganglion and its' significance. Methods In the cochlear paraffin slides. The immunohistochemistry technique was used to locate serotonin receptor IB in the spiral ganglion. Results Apositive signal was showed in the experimental group, as a negative signal was showed in the control group without serotonin receptor IB antibody. Conclusion The results demonstrate that the spiral ganglion neurons contain serotonin receptor IB. It strongly indicates that serotonin as a neurotransmitter plays an important role in regulating neural activity.

  12. Tumour necrosis factor alpha, interferon gamma and substance P are novel modulators of extrapituitary prolactin expression in human skin.

    Science.gov (United States)

    Langan, Ewan A; Vidali, Silvia; Pigat, Natascha; Funk, Wolfgang; Lisztes, Erika; Bíró, Tamás; Goffin, Vincent; Griffiths, Christopher E M; Paus, Ralf

    2013-01-01

    Human scalp skin and hair follicles (HFs) are extra-pituitary sources of prolactin (PRL). However, the intracutaneous regulation of PRL remains poorly understood. Therefore we investigated whether well-recognized regulators of pituitary PRL expression, which also impact on human skin physiology and pathology, regulate expression of PRL and its receptor (PRLR) in situ. This was studied in serum-free organ cultures of microdissected human scalp HFs and skin, i.e. excluding pituitary, neural and vascular inputs. Prolactin expression was confirmed at the gene and protein level in human truncal skin, where its expression significantly increased (p = 0.049) during organ culture. There was, however, no evidence of PRL secretion into the culture medium as measured by ELISA. PRL immunoreactivity (IR) in female human epidermis was decreased by substance P (p = 0.009), while neither the classical pituitary PRL inhibitor, dopamine, nor corticotropin-releasing hormone significantly modulated PRL IR in HFs or skin respectively. Interferon (IFN) γ increased PRL IR in the epithelium of human HFs (p = 0.044) while tumour necrosis factor (TNF) α decreased both PRL and PRLR IR. This study identifies substance P, TNFα and IFNγ as novel modulators of PRL and PRLR expression in human skin, and suggests that intracutaneous PRL expression is not under dopaminergic control. Given the importance of PRL in human hair growth regulation and its possible role in the pathogenesis of several common skin diseases, targeting intracutaneous PRL production via these newly identified regulatory pathways may point towards novel therapeutic options for inflammatory dermatoses.

  13. A synergistic effect of oestradiol and prolactin influencing the incidence of 3-methylcholanthrene induced cerivical carcinomas in mice.

    Science.gov (United States)

    Forsberg, J G; Breistein, L S

    1976-09-01

    Castrated NMRI mice were laparotomized and a thread impregnated with beeswax-methylcholanthrene was inserted into the uterine cervix. Beginning on the day of operation and for a further 5 days the animals were injected with oestradiol, prolactin, oestradiol-prolactin, oestradiol-prolactin-progesterone, or the solvents for the hormones only. One group of animals were injected with oestradiol-prolactin for 6 days and later with progesterone every third day until death. The animals were killed one or 4 weeks after the operation. Among the one-week animals the number of cervices presenting epithelial downgrowths ("buds") into the stroma was higher after treatment with a combination of oestradiol and prolactin than after treatment with each hormone separately or among the controls. Four weeks after operation, the incidence of squamous cervical carcinomas was seen to be significantly higher among animals injected with both oestradiol and prolactin than in controls or in those injected with oestradiol or prolactin alone. Progesterone had no definite effect on the oestradiol-prolactin induced incidence. The mechanism behind the synergistic effect of prolactin and oestradiol is discussed.

  14. The value of prolactin in inferior petrosal sinus sampling with desmopressin stimulation in Cushing's disease.

    Science.gov (United States)

    Qiao, Xiaona; Ye, Hongying; Zhang, Xiaolong; Zhao, Weiwei; Zhang, Shuo; Lu, Bin; Wang, Xuanchun; Zhang, Zhaoyun; Wu, Xi; He, Min; Zhao, Xiaolong; Li, Shiqi; Zhou, Linuo; Yang, Yehong; Hu, Renming; Li, Yiming

    2015-03-01

    Prolactin may reduce false-negative results in diagnosing Cushing's disease (CD) during inferior petrosal sinus sampling (IPSS). Prolactin normalization could improve the accuracy of IPSS in predicting adenoma lateralization in CD. However, none of the previous studies had involved the use of desmopressin during IPSS. Our objective was to examine the utility of prolactin measurement during IPSS with desmopressin stimulation. We conducted a retrospective analysis of 40 patients (including 31 females) with ACTH-dependent Cushing's syndrome who underwent IPSS between 2010 and 2013. Thirty-eight CD patients were partitioned into true positive (n = 35) and false negative (n = 3). The proportion of improper IPSS venous sampling defined by corresponding IPS:P (inferior petrosal sinus to peripheral) prolactin ratio prolactin-normalized ACTH IPS:P ratio >0.8 cutoff could increase the sensitivity of IPSS to 38/38 (100 %). Among the 31 patients with histopathologically proven adenoma localization, correct prediction of adenoma lateralization was obtained in 14/31 (45 %) patients by a peak intersinus ACTH gradient of ≥1.4 in baseline and was not improved by desmopressin stimulation. Left-right intersinus gradients of unilateral prolactin-adjusted ACTH IPS:P ratios could increase the correct prediction of adenoma lateralization to 20/31 (65 %) in baseline and 24/31 (77 %) (P = 0.006) after desmopressin stimulation, respectively. Prolactin is helpful to adjust negative results of IPSS with desmopressin stimulation. It may improve the accuracy in predicting adenoma lateralization in CD as well.

  15. Oncolytic Replication of E1b-Deleted Adenoviruses

    Directory of Open Access Journals (Sweden)

    Pei-Hsin Cheng

    2015-11-01

    Full Text Available Various viruses have been studied and developed for oncolytic virotherapies. In virotherapy, a relatively small amount of viruses used in an intratumoral injection preferentially replicate in and lyse cancer cells, leading to the release of amplified viral particles that spread the infection to the surrounding tumor cells and reduce the tumor mass. Adenoviruses (Ads are most commonly used for oncolytic virotherapy due to their infection efficacy, high titer production, safety, easy genetic modification, and well-studied replication characteristics. Ads with deletion of E1b55K preferentially replicate in and destroy cancer cells and have been used in multiple clinical trials. H101, one of the E1b55K-deleted Ads, has been used for the treatment of late-stage cancers as the first approved virotherapy agent. However, the mechanism of selective replication of E1b-deleted Ads in cancer cells is still not well characterized. This review will focus on three potential molecular mechanisms of oncolytic replication of E1b55K-deleted Ads. These mechanisms are based upon the functions of the viral E1B55K protein that are associated with p53 inhibition, late viralmRNAexport, and cell cycle disruption.

  16. LMX1B Mutations Cause Hereditary FSGS without Extrarenal Involvement

    Science.gov (United States)

    Boyer, Olivia; Woerner, Stéphanie; Yang, Fan; Oakeley, Edward J.; Linghu, Bolan; Gribouval, Olivier; Tête, Marie-Josèphe; Duca, José S.; Klickstein, Lloyd; Damask, Amy J.; Szustakowski, Joseph D.; Heibel, Françoise; Matignon, Marie; Baudouin, Véronique; Chantrel, François; Champigneulle, Jacqueline; Martin, Laurent; Nitschké, Patrick; Gubler, Marie-Claire; Johnson, Keith J.; Chibout, Salah-Dine

    2013-01-01

    LMX1B encodes a homeodomain-containing transcription factor that is essential during development. Mutations in LMX1B cause nail-patella syndrome, characterized by dysplasia of the patellae, nails, and elbows and FSGS with specific ultrastructural lesions of the glomerular basement membrane (GBM). By linkage analysis and exome sequencing, we unexpectedly identified an LMX1B mutation segregating with disease in a pedigree of five patients with autosomal dominant FSGS but without either extrarenal features or ultrastructural abnormalities of the GBM suggestive of nail-patella–like renal disease. Subsequently, we screened 73 additional unrelated families with FSGS and found mutations involving the same amino acid (R246) in 2 families. An LMX1B in silico homology model suggested that the mutated residue plays an important role in strengthening the interaction between the LMX1B homeodomain and DNA; both identified mutations would be expected to diminish such interactions. In summary, these results suggest that isolated FSGS could result from mutations in genes that are also involved in syndromic forms of FSGS. This highlights the need to include these genes in all diagnostic approaches to FSGS that involve next-generation sequencing. PMID:23687361

  17. Intestinal mucosal changes and upregulated calcium transporter and FGF-23 expression during lactation: Contribution of lactogenic hormone prolactin.

    Science.gov (United States)

    Wongdee, Kannikar; Teerapornpuntakit, Jarinthorn; Sripong, Chanakarn; Longkunan, Asma; Chankamngoen, Wasutorn; Keadsai, Chutiya; Kraidith, Kamonshanok; Krishnamra, Nateetip; Charoenphandhu, Narattaphol

    2016-01-15

    As the principal lactogenic hormone, prolactin (PRL) not only induces lactogenesis but also enhances intestinal calcium absorption to supply calcium for milk production. How the intestinal epithelium res-ponses to PRL is poorly understood, but it is hypothesized to increase mucosal absorptive surface area and calcium transporter expression. Herein, lactating rats were found to have greater duodenal, jejunal and ileal villous heights as well as cecal crypt depths than age-matched nulliparous rats. Morphometric analyses in the duodenum and cecum showed that their mucosal adaptations were diminished by bromocriptine, an inhibitor of pituitary PRL release. PRL also upregulated calcium transporter expression (e.g., TRPV6 and PMCA1b) in the duodenum of lactating rats. Since excessive calcium absorption could be detrimental to lactating rats, local negative regulator of calcium absorption, e.g., fibroblast growth factor (FGF)-23, should be increased. Immunohistochemistry confirmed the upregulation of FGF-23 protein expression in the duodenal and cecal mucosae of lactating rats, consistent with the enhanced FGF-23 mRNA expression in Caco-2 cells. Bromocriptine abolished this lactation-induced FGF-23 expression. Additionally, FGF-23 could negate PRL-stimulated calcium transport across Caco-2 monolayer. In conclusion, PRL was responsible for the lactation-induced mucosal adaptations, which were associated with compensatory increase in FGF-23 expression probably to prevent calcium hyperabsorption.

  18. Prolactin potentiates the activity of acid-sensing ion channels in female rat primary sensory neurons.

    Science.gov (United States)

    Liu, Ting-Ting; Qu, Zu-Wei; Ren, Cuixia; Gan, Xiong; Qiu, Chun-Yu; Hu, Wang-Ping

    2016-04-01

    Prolactin (PRL) is a polypeptide hormone produced and released from the pituitary and extrapituitary tissues. It regulates activity of nociceptors and causes hyperalgesia in pain conditions, but little is known the molecular mechanism. We report here that PRL can exert a potentiating effect on the functional activity of acid-sensing ion channels (ASICs), key sensors for extracellular protons. First, PRL dose-dependently increased the amplitude of ASIC currents with an EC50 of (5.89 ± 0.28) × 10(-8) M. PRL potentiation of ASIC currents was also pH dependent. Second, PRL potentiation of ASIC currents was blocked by Δ1-9-G129R-hPRL, a PRL receptor antagonist, and removed by intracellular dialysis of either protein kinase C inhibitor GF109203X, protein interacting with C-kinase 1(PICK1) inhibitor FSC-231, or PI3K inhibitor AS605240. Third, PRL altered acidosis-evoked membrane excitability of DRG neurons and caused a significant increase in the amplitude of the depolarization and the number of spikes induced by acid stimuli. Four, PRL exacerbated nociceptive responses to injection of acetic acid in female rats. Finally, PRL displayed a stronger effect on ASIC mediated-currents and nociceptive behavior in intact female rats than OVX female and male rats and thus modulation of PRL may be gender-dependent. These results suggest that PRL up-regulates the activity of ASICs and enhances ASIC mediated nociceptive responses in female rats, which reveal a novel peripheral mechanism underlying PRL involvement in hyperalgesia.

  19. Relative prolactin-to-progesterone concentrations around farrowing influence colostrum yield in primiparous sows.

    Science.gov (United States)

    Loisel, F; Farmer, C; van Hees, H; Quesnel, H

    2015-10-01

    In swine, colostrum production is induced by the drop of progesterone (P4) concentrations which leads to the prepartum peak of prolactin (PRL). PRL regulates mammary cell turnover and stimulates lacteal nutrient synthesis. P4 inhibits PRL secretion and downregulates the PRL receptor in the mammary gland. The aim of the present study was to determine if the relative prepartum concentrations of P4 and PRL (PRL/P4 ratio) influence sow colostrum production. The performance of 29 Landrace × Large White primiparous sows was analyzed. Colostrum yield was estimated during 24 h starting at the onset of parturition (T0) using litter weight gains. Colostrum was collected at T0 and 24 h later (T24). Repeated jugular blood samples were collected during the peripartum period, that is, from -72 to +24 h related to farrowing and were assayed for P4 and PRL. Sows were retrospectively categorized in 2 groups according to their PRL/P4 ratio 24 h before farrowing being either 3 (high PRL/P4, n = 13). During the peripartum period, the circulating concentrations of P4 were lower (P Colostrum yield was greater in high PRL/P4 compared with low PRL/P4 sows (4.11 vs 3.48 kg [root mean square error = 0.69], P Colostrum composition (dry matter, energy, protein, lipid, and lactose contents) and IgG and IgA concentrations did not differ between the 2 groups of sows (P > 0.10). The Na/K ratio in colostrum 24 h after the onset of farrowing was lower in high PRL/P4 compared with low PRL/P4 sows (P colostrum yield in primiparous sows.

  20. Prolactin circadian rhythm persists throughout lactation in women.

    Science.gov (United States)

    Stern, J M; Reichlin, S

    1990-01-01

    To determine whether the prolactin (PRL) circadian rhythm, with its characteristic nocturnal rise, persists during the hyperprolactinemia of lactation, PRL levels were analyzed in blood samples collected hourly for 24 h from 20 mothers, 4-46 months postpartum. The circadian rhythm of PRL persisted throughout lactation as manifested by: (1) significantly higher mean nighttime than daytime PRL levels in the whole sample, despite higher daytime nursing durations; (2) the distribution of zenith levels which most frequently occur between 23.00 and 07.00 h, when nursing duration is lowest, and which are almost absent between 07.00 and 23.00 h, when nursing duration is highest, and of nadir levels, which have an opposite pattern; (3) spontaneous PRL surges that are more frequent, longer, and of higher magnitude at night than during the day, and (4) the larger magnitude of suckling-induced PRL release from late afternoon through the night compared to the morning in some women. Our data suggest that the mechanisms responsible for the circadian rhythm in PRL secretion are relatively independent of the mechanisms of suckling-induced release. We propose that the nocturnal rise in PRL during lactation functions to ensure a robust milk supply during an extensive nonsuckling interval.

  1. Gender-related differences in prolactin secretion in pituitary prolactinomas

    Energy Technology Data Exchange (ETDEWEB)

    Nishioka, H.; Haraoka, J.; Akada, K.; Azuma, S. [Department of Neurosurgery, Tokyo Medical University (Japan)

    2002-05-01

    In pituitary prolactinomas, serum prolactin (PRL) levels usually parallel the tumor size. We conducted a retrospective study to determine differences in PRL production between men and women with prolactinomas. A total of 51 patients, 16 men and 35 women, was studied. We investigated clinical, endocrinological, radiological and histological findings, and estimated the tumor volume (TV) by high-resolution magnetic resonance imaging (MRI). Correlation between PRL level and TV was low in men (R=0.458), in contrast to women (R=0.953), c. Men with prolactinomas showed predominance of large tumors (P=0.0009) with high PRL levels (P=0.0009) and had greater tendencies for cyst formation (P=0.0047). Large prolactinomas tended to be accompanied by cyst(s) (P=0.0051) and hemorrhage (P=0.0015), both of which were associated with reduced PRL secretion (P=0.0004 and P<0.0001, respectively). When the volume of the cysts and hemorrhage was subtracted from the total TV, correlation between PRL level and TV became greater (R=0.905) with no gender difference. Histological examination demonstrated a sparsely granulated type of lactotroph adenoma with occasional fibrosis, particularly in tumors with hemorrhage and cysts. Although a significant discrepancy between PRL level and TV may exist in prolactinomas when intratumoral hemorrhage and/or cysts are present, there is no essential difference in PRL secretion between the sexes. (orig.)

  2. Bovine lactotroph cultures for the study of prolactin synthesis functions.

    Science.gov (United States)

    Wang, Jianfa; Yang, Zhanqing; Fu, Shoupeng; Liu, Bingrun; Wu, Dianjun; Wang, Wei; Sun, Dongbo; Wu, Rui; Liu, Juxiong

    2016-03-01

    The aim of this study was to establish a bovine anterior pituitary-derived lactotroph (BAPDL) line that expresses prolactin (PRL) in vitro to study the mechanisms of bovine PRL synthesis and secretion. Immunohistochemistry assay of PRL in the newborn calves' anterior pituitary glands showed that most lactotrophs were located within the superior border of the lateral wings of the anterior pituitary. Tissues of the superior border of the lateral wings of the anterior pituitary were dispersed and cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum (FBS). The limiting dilution method was used to establish BAPDL from single cell clone. BAPDL cells constantly expressed mRNAs for PRL and pituitary-specific transcription factor 1 (Pit-1) gene and grew steadily and rapidly in the DMEM supplemented with 10% FBS. PRL immunoreactivity was present in BAPDL at passage 20. The concentration of bovine PRL in BAPDL at passage 20 culture supernatant was decreased to below 35% compared with that in BAPDL at passage 1. The effects of human epidermal growth factor (hEGF) and dopamine (DA) on the expression and secretion of PRL in BAPDL at passage 4 were also investigated. The results are consistent with those of previous studies. Thus, it can be used successfully for studying the mechanisms of stimuli regulating PRL synthesis and release.

  3. Multiple metals predict prolactin and thyrotropin (TSH) levels in men

    Energy Technology Data Exchange (ETDEWEB)

    Meeker, John D., E-mail: meekerj@umich.edu [Department of Environmental Health Sciences, University of Michigan School of Public Health, 6635 SPH Tower, 109 S. Observatory St., Ann Arbor, MI 48109 (United States); Rossano, Mary G. [Department of Animal and Food Sciences, University of Kentucky, Lexington, KY (United States); Protas, Bridget [Department of Epidemiology, Michigan State University, East Lansing, MI (United States); Diamond, Michael P.; Puscheck, Elizabeth [Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI (United States); Daly, Douglas [Grand Rapids Fertility and IVF, Grand Rapids, MI (United States); Paneth, Nigel [Department of Obstetrics and Gynecology, Michigan State University, East Lansing, MI (United States); Wirth, Julia J. [Department of Epidemiology, Michigan State University, East Lansing, MI (United States); Department of Obstetrics and Gynecology, Michigan State University, East Lansing, MI (United States)

    2009-10-15

    Exposure to a number of metals can affect neuroendocrine and thyroid signaling, which can result in adverse effects on development, behavior, metabolism, reproduction, and other functions. The present study assessed the relationship between metal concentrations in blood and serum prolactin (PRL) and thyrotropin (TSH) levels, markers of dopaminergic, and thyroid function, respectively, among men participating in a study of environmental influences on male reproductive health. Blood samples from 219 men were analyzed for concentrations of 11 metals and serum levels of PRL and TSH. In multiple linear regression models adjusted for age, BMI and smoking, PRL was inversely associated with arsenic, cadmium, copper, lead, manganese, molybdenum, and zinc, but positively associated with chromium. Several of these associations (Cd, Pb, Mo) are consistent with limited studies in humans or animals, and a number of the relationships (Cr, Cu, Pb, Mo) remained when additionally considering multiple metals in the model. Lead and copper were associated with non-monotonic decrease in TSH, while arsenic was associated with a dose-dependent increase in TSH. For arsenic these findings were consistent with recent experimental studies where arsenic inhibited enzymes involved in thyroid hormone synthesis and signaling. More research is needed for a better understanding of the role of metals in neuroendocrine and thyroid function and related health implications.

  4. Prolactin family of the guinea pig, Cavia porcellus.

    Science.gov (United States)

    Alam, S M Khorshed; Konno, Toshihiro; Rumi, M A Karim; Dong, Yafeng; Weiner, Carl P; Soares, Michael J

    2010-08-01

    Prolactin (PRL) is a multifunctional hormone with prominent roles in regulating growth and reproduction. The guinea pig (Cavia porcellus) has been extensively used in endocrine and reproduction research. Thus far, the PRL cDNA and protein have not been isolated from the guinea pig. In the present study, we used information derived from the public guinea pig genome database as a tool for identifying guinea pig PRL and PRL-related proteins. Guinea pig PRL exhibits prominent nucleotide and amino acid sequence differences when compared with PRLs of other eutherian mammals. In contrast, guinea pig GH is highly conserved. Expression of PRL and GH in the guinea pig is prominent in the anterior pituitary, similar to known expression patterns of PRL and GH for other species. Two additional guinea pig cDNAs were identified and termed PRL-related proteins (PRLRP1, PRLRP2). They exhibited a more distant relationship to PRL and their expression was restricted to the placenta. Recombinant guinea pig PRL protein was generated and shown to be biologically active in the PRL-responsive Nb2 lymphoma cell bioassay. In contrast, recombinant guinea pig PRLRP1 protein did not exhibit PRL-like bioactivity. In summary, we have developed a new set of research tools for investigating the biology of the PRL family in an important animal model, the guinea pig.

  5. Prolactin stimulates precursor cells in the adult mouse hippocampus.

    Directory of Open Access Journals (Sweden)

    Tara L Walker

    Full Text Available In the search for ways to combat degenerative neurological disorders, neurogenesis-stimulating factors are proving to be a promising area of research. In this study, we show that the hormonal factor prolactin (PRL can activate a pool of latent precursor cells in the adult mouse hippocampus. Using an in vitro neurosphere assay, we found that the addition of exogenous PRL to primary adult hippocampal cells resulted in an approximate 50% increase in neurosphere number. In addition, direct infusion of PRL into the adult dentate gyrus also resulted in a significant increase in neurosphere number. Together these data indicate that exogenous PRL can increase hippocampal precursor numbers both in vitro and in vivo. Conversely, PRL null mice showed a significant reduction (approximately 80% in the number of hippocampal-derived neurospheres. Interestingly, no deficit in precursor proliferation was observed in vivo, indicating that in this situation other niche factors can compensate for a loss in PRL. The PRL loss resulted in learning and memory deficits in the PRL null mice, as indicated by significant deficits in the standard behavioral tests requiring input from the hippocampus. This behavioral deficit was rescued by direct infusion of recombinant PRL into the hippocampus, indicating that a lack of PRL in the adult mouse hippocampus can be correlated with impaired learning and memory.

  6. Epigenetic and genetic variants in the HTR1B gene and clinical improvement in children and adolescents treated with fluoxetine.

    Science.gov (United States)

    Gassó, Patricia; Rodríguez, Natalia; Blázquez, Ana; Monteagudo, Ana; Boloc, Daniel; Plana, Maria Teresa; Lafuente, Amalia; Lázaro, Luisa; Arnaiz, Joan Albert; Mas, Sergi

    2017-04-03

    The serotonin 1B receptor (5-HT1B) is important to both the pathogenesis of major depressive disorder and the antidepressant effects of selective serotonin reuptake inhibitors. Although fluoxetine has been shown to be effective and safe in children and adolescents, not all patients experience a proper clinical response, which has led to further study into the main factors involved in this inter-individual variability. Our aim was to study the effect of epigenetic and genetic factors that could affect 5-hydroxytryptamine receptor 1B (HTR1B) gene expression, and thereby response to fluoxetine. A total of 83 children and adolescents were clinically assessed 12weeks after of initiating an antidepressant treatment with fluoxetine for the first time. We evaluated the influence of single nucleotide polymorphisms (SNPs) specifically located in transcription factor binding sites (TFBSs) on their clinical improvement. A combined genetic analysis considering the significant SNPs together with the functional variant rs130058 previously associated in our population was also performed. Moreover, we assessed, for the first time in the literature, whether methylation levels of the HTR1B promoter region could be associated with the pharmacological response. Two, rs9361233 and rs9361235, were significantly associated with clinical improvement after treatment with fluoxetine. The heterozygous genotype combination analysis showed a negative correlation with clinical improvement. The lowest improvement was experienced by patients who were heterozygous for all three SNPs. Moreover, a negative correlation was found between clinical improvement and the average methylation level of the HTR1B promoter. These results give new evidence for the role of epigenetic and genetic factors which could modulate HTR1B expression in the pharmacological response to antidepressants.

  7. Cloning of ovine Prolactin Releasing Hormone and Its Receptor Gene and Their Different Expression in the HPG Axis%绵羊 PRLH 及其受体基因的克隆及在下丘脑-垂体-性腺轴中差异表达的研究

    Institute of Scientific and Technical Information of China (English)

    赵强; 马友记; 李菁华

    2015-01-01

    To explore the expression of PRLH and its receptor gene in sheep gonadal axis , we successfully cloned the PRLH and receptor gene in organizations at the hypothalamic-pituitary-gonadal axis by used the sheep as experimental animal ,got the phylogenetic tree .Also we used qRT-PCR technology to research different expression of PRLH and its receptor gene in different tissues at HPG axis .The results showed that sheep PRLH and PRLHR nu-cleotide sequences of mRNA were 113,237 bp.PRLH gene nucleotide sequence and goats ,cattle,human,mouse ho-mology were 96.8%,93.3%,80.3%,74.6%.PRLHR gene and the Tibetan antelope , goat, cattle, human and mouse homology were 100%,99.3%,97.3%,90.4%,84.4%.PRLH and its receptor gene in sheep hypothala-mus,pituitary,uterine and ovary were expressed ,and the expression of PRLH gene in hypothalamus ,pituitary and o-vary was significantly less than the uterine ( P0.05).So the hypothalamus,pituitary,o-vary and uterus were the main organ for the synthesis of secretion .%为了探讨PRLH及其受体基因在绵羊性腺轴中的表达,以绵羊下丘脑-垂体-性腺轴系为研究对象,克隆了PRLH及其受体基因PRLHR,构建了系统进化树,并利用qRT-PCR技术对PRLH及其受体基因在绵羊性腺轴中不同组织的表达差异做了研究。结果表明,绵羊PRLH和PRLHR mRNA核苷酸序列分别为113,237 bp,PRLH基因核苷酸序列与山羊、牛、人、小鼠的同源性分别为96.8%,93.3%,80.3%,74.6%,PRLHR基因与藏羚羊、山羊、牛、人和小鼠的同源性分别为100%,99.3%,97.3%,90.4%,84.4%;PRLH及其受体基因在绵羊的下丘脑、垂体、子宫和卵巢中均有一定量的表达,且PRLH基因在下丘脑、垂体和卵巢中的表达要显著低于子宫( P<0.05);PRLHR在子宫与垂体中的表达差异显著( P<0.05),其他差异不明显。说明下丘脑、垂体、子宫和卵巢是PRLH合成分泌和发挥作用的主要器官。

  8. Update on Melatonin Receptors. IUPHAR Review. : Melatonin Receptors

    OpenAIRE

    Jockers, Ralf; Delagrange, Philippe; Dubocovich, Margarita ,; Markus, Regina ,; Renault, Nicolas; Tosini, Gianluca; Cecon, Erika; Zlotos, Darius Paul

    2016-01-01

    International audience; Melatonin receptors are seven transmembrane-spanning proteins belonging to the G protein-coupled receptor super-family. In mammals, two melatonin receptor subtypes exit MT1 and MT2 encoded by the MTNR1A and MTNR1B genes, respectively. The current review provides an update on melatonin receptors by the corresponding sub-committee of the International Union of Basic and Clinical Pharmacology. We will highlight recent developments of melatonin receptor ligands, including ...

  9. Ahcyl2 upregulates NBCe1-B via multiple serine residues of the PEST domain-mediated association.

    Science.gov (United States)

    Park, Pil Whan; Ahn, Jeong Yeal; Yang, Dongki

    2016-07-01

    Inositol-1,4,5-triphosphate [IP3] receptors binding protein released with IP3 (IRBIT) was previously reported as an activator of NBCe1-B. Recent studies have characterized IRBIT homologue S-Adenosylhomocysteine hydrolase-like 2 (AHCYL2). AHCYL2 is highly homologous to IRBIT (88%) and heteromerizes with IRBIT. The two important domains in the N-terminus of AHCYL2 are a PEST domain and a coiled-coil domain which are highly comparable to those in IRBIT. Therefore, in this study, we tried to identify the role of those domains in mouse AHCYL2 (Ahcyl2), and we succeeded in identifying PEST domain of Ahcyl2 as a regulation region for NBCe1-B activity. Site directed mutagenesis and coimmunoprecipitation assay showed that NBCe1-B binds to the N-terminal Ahcyl2-PEST domain, and its binding is determined by the phosphorylation of 4 critical serine residues (Ser151, Ser154, Ser157, and Ser160) in Ahcyl2 PEST domain. Also we revealed that 4 critical serine residues in Ahcyl2 PEST domain are indispensable for the activation of NBCe1-B using measurement of intracellular pH experiment. Thus, these results suggested that the NBCe1-B is interacted with 4 critical serine residues in Ahcyl2 PEST domain, which play an important role in intracellular pH regulation through NBCe1-B.

  10. Tired of diabetes genetics? Circadian rhythms and diabetes: the MTNR1B story?

    Science.gov (United States)

    Nagorny, Cecilia; Lyssenko, Valeriya

    2012-12-01

    Circadian rhythms are ubiquitous in biological systems and regulate metabolic processes throughout the body. Misalliance of these circadian rhythms and the systems they regulate has a profound impact on hormone levels and increases risk of developing metabolic diseases. Melatonin, a hormone secreted by the pineal gland, is one of the major signaling molecules used by the master circadian oscillator to entrain downstream circadian rhythms. Several recent genetic studies have pointed out that a common variant in the gene that encodes the melatonin receptor 2 (MTNR1B) is associated with impaired glucose homeostasis, reduced insulin secretion, and an increased risk of developing type 2 diabetes. Here, we try to review the role of this receptor and its signaling pathways in respect to glucose homeostasis and development of the disease.

  11. Plasma prolactin, renin and catecholamines in young normotensive and borderline hypertensive subjects.

    Science.gov (United States)

    Saito, I; Takeshita, E; Saruta, T; Nagano, S; Sekihara, T

    1984-02-01

    It has been reported that patients with essential hypertension have high plasma prolactin levels and suggested that reduced central dopaminergic activity may be a factor in the pathogenesis of essential hypertension. This study examines the influence of posture on plasma prolactin, plasma catecholamines, plasma renin activity, blood pressure and heart rate in 24 patients with borderline hypertension (age 19 +/- 1 years) and 20 normotensive subjects matched for age and body mass index. Supine plasma prolactin levels were similar in both groups [borderline hypertension, 11.3 +/- 0.7 ng/ml; normotensive, 10.7 +/- 0.8 ng/ml (mean +/- s.e.m.)] and no increase in plasma prolactin was observed after 10 min standing in both groups. Normotensive and borderline hypertensive subjects had similar values for supine and upright plasma renin activity and plasma norepinephrine. There were no significant correlations between supine plasma prolactin and supine blood pressure, supine plasma renin activity or plasma norepinephrine when data from both normotensive and borderline hypertensive subjects were combined. These results may provide indirect evidence against the occurrence of reduced central dopaminergic activity in borderline hypertension.

  12. Prolactin and macroprolactin levels in psychiatric patients receiving atypical antipsychotics: A preliminary study.

    Science.gov (United States)

    Park, Young-Min; Lee, Seung-Hwan; Lee, Bun-Hee; Lee, Kyu Young; Lee, Kye-Seong; Kang, Seung-Gul; Lee, Hwa-Young; Kim, Won

    2016-05-30

    The aims of this study were to clarify whether atypical antipsychotics can elevate serum levels of both macroprolactin and prolactin, and whether the macroprolactin levels differ according to the type of atypical antipsychotic being taken. In total, 245 subjects were enrolled consecutively in 6 hospitals. Serum prolactin and macroprolactin levels were measured at a single time point during maintenance antipsychotic monotherapy. The mean total serum prolactin levels including macroprolactin were 11.91, 20.73, 16.41, 50.83, 12.84, and 59.1ng/mL for patients taking aripiprazole, blonanserin, olanzapine, paliperidone, quetiapine, and risperidone, respectively, while those for macroprolactin were 1.71, 3.86, 3.73, 7.28, 2.77, and 8.0ng/mL. The total prolactin and macroprolactin levels were significantly higher among those taking paliperidone and risperidone than among those taking any of the other antipsychotics (pprolactin and macroprolactin. Sexual dysfunction was reported in 35.5% (87/245) of the total subjects. However, the total prolactin level did not differ significantly between subjects with and without sexual dysfunction except gynecomastia. These findings suggest that treatment with risperidone and paliperidone can induce hyperprolactinemia and macroprolactinemia in psychiatric patients.

  13. A tale of two rhythms: the emerging roles of oxytocin in rhythmic prolactin release.

    Science.gov (United States)

    Bertram, R; Helena, C V; Gonzalez-Iglesias, A E; Tabak, J; Freeman, M E

    2010-07-01

    Hormone secretion often occurs in a pulsatile manner. In this review, we discuss two rhythms of in vivo prolactin release in female rats and the ongoing research that we and others have performed aiming to understand the mechanisms underlying them. The peptide hormone oxytocin appears to play an important role in both rhythms. One rhythm occurs during the first half of pregnancy, but can also be induced in ovariectomised rats. This is characterised by a circadian pattern with two prolactin surges per day. Two methods for triggering this rhythm are discussed, each utilising a unique physiological pathway that includes oxytocin action, presumably on pituitary lactotrophs. The second rhythm occurs during the oestrous cycle and is characterised by a surge of prolactin on the afternoon of pro-oestrus. We discuss recent findings that oxytocin is more effective at stimulating prolactin release from lactotrophs taken from animals on the afternoon of pro-oestrus than from those of animals on the morning of dioestrus 1, raising the possibility that this hormone plays a physiological role in the regulation of prolactin secretion during the oestrous cycle.

  14. Anthrax lethal toxin induced lysosomal membrane permeabilization and cytosolic cathepsin release is Nlrp1b/Nalp1b-dependent.

    Directory of Open Access Journals (Sweden)

    Kathleen M Averette

    Full Text Available NOD-like receptors (NLRs are a group of cytoplasmic molecules that recognize microbial invasion or 'danger signals'. Activation of NLRs can induce rapid caspase-1 dependent cell death termed pyroptosis, or a caspase-1 independent cell death termed pyronecrosis. Bacillus anthracis lethal toxin (LT, is recognized by a subset of alleles of the NLR protein Nlrp1b, resulting in pyroptotic cell death of macrophages and dendritic cells. Here we show that LT induces lysosomal membrane permeabilization (LMP. The presentation of LMP requires expression of an LT-responsive allele of Nlrp1b, and is blocked by proteasome inhibitors and heat shock, both of which prevent LT-mediated pyroptosis. Further the lysosomal protease cathepsin B is released into the cell cytosol and cathepsin inhibitors block LT-mediated cell death. These data reveal a role for lysosomal membrane permeabilization in the cellular response to bacterial pathogens and demonstrate a shared requirement for cytosolic relocalization of cathepsins in pyroptosis and pyronecrosis.

  15. Superoxide anion radicals induce IGF-1 resistance through concomitant activation of PTP1B and PTEN.

    Science.gov (United States)

    Singh, Karmveer; Maity, Pallab; Krug, Linda; Meyer, Patrick; Treiber, Nicolai; Lucas, Tanja; Basu, Abhijit; Kochanek, Stefan; Wlaschek, Meinhard; Geiger, Hartmut; Scharffetter-Kochanek, Karin

    2015-01-01

    The evolutionarily conserved IGF-1 signalling pathway is associated with longevity, metabolism, tissue homeostasis, and cancer progression. Its regulation relies on the delicate balance between activating kinases and suppressing phosphatases and is still not very well understood. We report here that IGF-1 signalling in vitro and in a murine ageing model in vivo is suppressed in response to accumulation of superoxide anions (O2∙-) in mitochondria, either by chemical inhibition of complex I or by genetic silencing of O2∙--dismutating mitochondrial Sod2. The O2∙--dependent suppression of IGF-1 signalling resulted in decreased proliferation of murine dermal fibroblasts, affected translation initiation factors and suppressed the expression of α1(I), α1(III), and α2(I) collagen, the hallmarks of skin ageing. Enhanced O2∙- led to activation of the phosphatases PTP1B and PTEN, which via dephosphorylation of the IGF-1 receptor and phosphatidylinositol 3,4,5-triphosphate dampened IGF-1 signalling. Genetic and pharmacologic inhibition of PTP1B and PTEN abrogated O2∙--induced IGF-1 resistance and rescued the ageing skin phenotype. We thus identify previously unreported signature events with O2∙-, PTP1B, and PTEN as promising targets for drug development to prevent IGF-1 resistance-related pathologies.

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

    Energy Technology Data Exchange (ETDEWEB)

    Mai, Leemin (National Yang-Ming Medical College, Taipei (Taiwan)); Pan, Jenntser (Michigan State Univ., East Lansing (USA))

    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 {mu}g/rat stimulated a moderate PRL release in the morning and lower doses were without effect. Vasopressin was most effective at a dose of 5 {mu}g/rat in stimulating PRL release, while consecutive injections of higher doses were less effective. In contrast, TRH, ranging from 1 to 8 {mu}g/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.

  17. Leptin induces CYP1B1 expression in MCF-7 cells through ligand-independent activation of the ERα pathway

    Energy Technology Data Exchange (ETDEWEB)

    Khanal, Tilak; Kim, Hyung Gyun; Do, Minh Truong; Choi, Jae Ho; Won, Seong Su [Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon (Korea, Republic of); Kang, Wonku [College of Pharmacy, Yeungnam University, Gyeongsan (Korea, Republic of); Chung, Young Chul [Department of Food Science and Culinary, International University of Korea, Jinju (Korea, Republic of); Jeong, Tae Cheon, E-mail: taecheon@ynu.ac.kr [College of Pharmacy, Yeungnam University, Gyeongsan (Korea, Republic of); Jeong, Hye Gwang, E-mail: hgjeong@cnu.ac.kr [Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon (Korea, Republic of)

    2014-05-15

    Leptin, a hormone with multiple biological actions, is produced predominantly by adipose tissue. Among its functions, leptin can stimulate tumour cell growth. Oestrogen receptor α (ERα), which plays an essential role in breast cancer development, can be transcriptionally activated in a ligand-independent manner. In this study, we investigated the effect of leptin on CYP1B1 expression and its mechanism in breast cancer cells. Leptin induced CYP1B1 protein, messenger RNA expression and promoter activity in ERα-positive MCF-7 cells but not in ERα-negative MDA-MB-231 cells. Additionally, leptin increased 4-hydroxyoestradiol in MCF-7 cells. Also, ERα knockdown by siRNA significantly blocked the induction of CYP1B1 expression by leptin, indicating that leptin induced CYP1B1 expression via an ERα-dependent mechanism. Transient transfection with CYP1B1 deletion promoter constructs revealed that the oestrogen response element (ERE) plays important role in the up-regulation of CYP1B1 by leptin. Furthermore, leptin stimulated phosphorylation of ERα at serine residues 118 and 167 and increased ERE-luciferase activity, indicating that leptin induced CYP1B1 expression by ERα activation. Finally, we found that leptin activated ERK and Akt signalling pathways, which are upstream kinases related to ERα phosphorylation induced by leptin. Taken together, our results indicate that leptin-induced CYP1B1 expression is mediated by ligand-independent activation of the ERα pathway as a result of the activation of ERK and Akt in MCF-7 cells. - Highlights: • Leptin increased 4-hydroxyoestradiol in MCF-7 breast cancer cells. • Leptin activated ERK and Akt kinases related to ERα phosphorylation. • Leptin induces phosphorylation of ERα at serine residues 118 and 167. • Leptin induces ERE-luciferase activity.

  18. Origin of vestibular dysfunction in Usher syndrome type 1B.

    NARCIS (Netherlands)

    Sun, J.; Alphen, A.M. van; Wagenaar, M.; Huygen, P.L.M.; Hoogenraad, C.C.; Hasson, T.; Koekkoek, S.K.; Bohne, B.A.; Zeeuw, C.I. de

    2001-01-01

    It is still debated to what extent the vestibular deficits in Usher patients are due to either central vestibulocerebellar or peripheral vestibular problems. Here, we determined the origin of the vestibular symptoms in Usher 1B patients by subjecting them to compensatory eye movement tests and by in

  19. PTP1B targets the endosomal sorting machinery

    DEFF Research Database (Denmark)

    Stuible, Matthew; Abella, Jasmine V; Feldhammer, Matthew;

    2010-01-01

    STAM2 specifically suppressed Akt activation, and a phosphorylation-deficient STAM2 mutant displayed prolonged localization on endosomes following EGF stimulation. These results reveal a novel link between the dephosphorylation and endocytic machinery and suggest that PTP1B can affect RTK signaling...

  20. Influence of prolactin administration on the ultimobranchial body and parathyroid glands of the freshwater snake, Natrix piscator.

    Science.gov (United States)

    Srivastav, A K; Rani, L; Sasayama, Y

    1994-05-01

    The effects of ovine prolactin (10 I.U./100 g body wt) on the ultimobranchial body and parathyroid glands were investigated in Natrix piscator for 15 days. The ultimobranchial body of the prolactin treated specimens depicts signs of increased activity whereas the parathyroid glands exhibit reduced activity.

  1. Levels of prolactin in relation to coagulation factors and risk of venous thrombosis. Results of a large population-based case-control study (MEGA-study)

    NARCIS (Netherlands)

    Stuijver, D.J.; Debeij, J.; Zaane, B. van; Dekkers, O.M.; Smit, J.W.A.; Buller, H.R.; Rosendaal, F.R.; Gerdes, V.E.; Cannegieter, S.C.

    2012-01-01

    The pituitary hormone prolactin is thought to influence coagulation. We aimed to study the relation between prolactin levels, coagulation factors and risk of venous thrombosis (VT). We used data from a large population based case-control study into aetiology of first VT (MEGA-study). Prolactin level

  2. Hostility is associated with a low prolactin response to meta-chlorophenylpiperazine in abstinent alcoholics.

    Science.gov (United States)

    Handelsman, L; Holloway, K; Kahn, R S; Sturiano, C; Rinaldi, P J; Bernstein, D P; Siever, L; Gabriel, S; Cooper, T B

    1996-08-01

    The prolactin response to the administration of serotonin agonists is an index of central nervous system serotonin (5HT) activity. This index is blunted in association with hostile aggression in personality-disordered individuals without substance abuse. We tested whether prolactin response to the partial 5HT agonist meta-chlorophenylpiperazine (MCPP) (0.35 mg/kg po) was associated with measures of trait hostility in alcoholics who were completing a 3-week rehabilitation program after medical detoxification. We also tested whether the same 5HT index differed in the group of alcoholics compared with the healthy volunteers. The prolactin response to MCPP was inversely associated with the main index of trait hostility and was similarly inversely associated with an index of depression. There was, however, no difference in neuroendocrine or temperature responses to MCPP between the alcohol-dependent group and the healthy volunteers.

  3. Treatment of Aggressive Prolactin-Secreting Pituitary Adenomas with Adjuvant Temozolomide Chemotherapy: A Review.

    Science.gov (United States)

    Moisi, Marc; Cruz, Aurora S; Benkers, Tara; Rostad, Steven; Broyles, Frances Broyles; Yuen, Kevin; Mayberg, Marc

    2016-01-01

    Most prolactin-secreting pituitary adenomas demonstrate slow growth and are effectively managed with medical/surgical therapy. Rarely, these tumors can behave aggressively with rapid growth and invasion of local tissues, and are refractory to medical, surgical, or radio-surgical therapies. We report a case of a prolactin-secreting adenoma in a young woman, which became progressively aggressive and refractory to usual treatment modalities, but responded to treatment with the chemotherapeutic agent temozolomide. In addition, we review the literature for treatment of refractory adenomas with temozolomide. The clinical and pathologic characteristics of aggressive prolactin-secreting adenomas are reviewed, as well as their response to dopamine agonists, surgery, radiotherapy, and chemotherapy.

  4. Radioimmunoassay of human homologous prolactin in serum with commercially available reagents. [/sup 125/I tracer technique

    Energy Technology Data Exchange (ETDEWEB)

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

    1977-09-01

    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 (..mu..g/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.

  5. Effects of central infusion of ghrelin on food intake and plasma levels of growth hormone, luteinizing hormone, prolactin, and cortisol secretion in sheep.

    Science.gov (United States)

    Iqbal, Javed; Kurose, Yohei; Canny, Benedict; Clarke, Iain J

    2006-01-01

    Ghrelin is an endogenous ligand for the GH secretagogue/ghrelin receptor (GHS-R) and stimulates feeding behavior and GH levels in rodents and humans. A preprandial increase in plasma ghrelin levels is seen in sheep on programmed feeding, followed by a postprandial rise in plasma GH levels, but effects on food intake and endocrine function are not defined in this ruminant species. We administered ghrelin to female sheep in various modes and measured effects on voluntary food intake (VFI) and plasma levels of GH, LH, prolactin, and cortisol. Whether administered intracerebroventricularly or iv, ghrelin consistently failed to stimulate VFI. On the other hand, ghrelin invariably increased plasma GH levels and alpha,beta-diaminopropanoic acid-octanoyl3 human ghrelin was more potent than ovine ghrelin. Bolus injection of ghrelin into the third cerebral ventricle reduced plasma LH levels but did not affect levels of prolactin or cortisol. These findings suggested that the preprandial rise in plasma ghrelin that is seen in sheep on programmed feeding does not influence VFI but is likely to be important in the postprandial rise in GH levels. Thus, ghrelin does not appear to be a significant regulator of ingestive behavior in this species of ruminant but acts centrally to indirectly regulate GH and LH secretion.

  6. Prolactin as an Adjunct for Type 1 Diabetes Immunotherapy.

    Science.gov (United States)

    Hyslop, Colin M; Tsai, Sue; Shrivastava, Vipul; Santamaria, Pere; Huang, Carol

    2016-01-01

    Type 1 diabetes is caused by autoimmune destruction of β-cells. Although immunotherapy can restore self-tolerance thereby halting continued immune-mediated β-cell loss, residual β-cell mass and function is often insufficient for normoglycemia. Using a growth factor to boost β-cell mass can potentially overcome this barrier and prolactin (PRL) may fill this role. Previous studies have shown that PRL can stimulate β-cell proliferation and up-regulate insulin synthesis and secretion while reducing lymphocytic infiltration of islets, suggesting that it may restore normoglycemia through complementary mechanisms. Here, we test the hypothesis that PRL can improve the efficacy of an immune modulator, the anticluster of differentiation 3 monoclonal antibody (aCD3), in inducing diabetes remission by up-regulating β-cell mass and function. Diabetic nonobese diabetic (NOD) mice were treated with a 5-day course of aCD3 with or without a concurrent 3-week course of PRL. We found that a higher proportion of diabetic mice treated with the aCD3 and PRL combined therapy achieved diabetes reversal than those treated with aCD3 alone. The aCD3 and PRL combined group had a higher β-cell proliferation rate, an increased β-cell fraction, larger islets, higher pancreatic insulin content, and greater glucose-stimulated insulin release. Lineage-tracing analysis found minimal contribution of β-cell neogenesis to the formation of new β-cells. Although we did not detect a significant difference in the number or proliferative capacity of T cells, we observed a higher proportion of insulitis-free islets in the aCD3 and PRL group. These results suggest that combining a growth factor with an immunotherapy may be an effective treatment paradigm for autoimmune diabetes.

  7. Secretory patterns of prolactin in dogs: circannual and ultradian rhythms.

    Science.gov (United States)

    Corrada, Y; Castex, G; Sosa, Y; Gobello, C

    2003-06-01

    The objectives of the present study were to characterize in dogs circannual and ultradian prolactin (PRL) secretory patterns and also to compare gender differences in the ultradian period of study in the Southern hemisphere. Blood samples were collected at 15-min intervals for 2.5 h from seven male and seven female dogs and a single monthly sampling, over a 1-year time span, from six male dogs for the ultradian and circannual studies, respectively. Plasma PRL was measured by a homologous enzyme immunometric assay. The ultradian study evidenced PRL elevations suggesting pulsatile secretion in both genders. Significantly higher mean smoothed baseline (ng / ml [7.02 +/- 1.2 vs 1.23 +/- 1.0, p < 0.01]) and AUC (ng/ml * 2.5 h [25.2 +/- 3.8 vs 4.4 +/- 3.8, p < 0.01]) were found in females when compared with males. In the circannual study, plasma PRL concentrations did not statistically differ among the months of the year. When grouped together the 3 months with a longer daylight had significantly higher PRL concentrations than the 3 months with the shortest (2.31 +/- 0.37 vs 0.96 +/- 0.37, p < 0.01). The correlation between length of daylight and PRL concentrations was 0.24, p < 0.05. It is concluded that PRL does have a circannual rhythmicity and that there are ultradian gender-related differences in the period under study in these groups of dogs. This study also demonstrates plasma PRL elevations suggesting pulsatile secretion in male dogs.

  8. Biochemical and pharmacological characterization of the thyrotropin releasing hormone (TRH) receptor from clonal GH sub 4 C sub 1 pituitary cells

    Energy Technology Data Exchange (ETDEWEB)

    Phillips, W.J.

    1987-01-01

    The effect of drugs with anesthetic properties on the activity of the pituitary thyrotropin-releasing hormone (TRH) receptor was determined in the clonal GH{sub 4}C{sub 1} somatomammotropic cell line. Classic local anesthetics and other drugs with anesthetic activity inhibited binding of ({sup 3}H)methyl-TRH to cell receptors at concentrations known to produce anesthetic effects on the membrane. The inhibition of TRH receptor binding by tetracaine was competitive and temperature and pH dependent. Verapamil and tetracaine inhibited TRH-stimulated prolactin secretion at concentrations that inhibited peptide binding. TRH-stimulated prolactin secretion was equivalent with or without Ca{sup 2+} channel activity. Verapamil and tetracaine also inhibited basal prolactin and secretion stimulated by drugs that bypass membrane receptors, db-cAMP and TPA. These results indicate that inhibition of TRH binding and responses by diverse drugs results from an anesthetic effect on the cell membrane.

  9. Granulosa Cell-Expressed BMPR1A and BMPR1B Have Unique Functions in Regulating Fertility but Act Redundantly to Suppress Ovarian Tumor Development

    Science.gov (United States)

    Edson, Mark A.; Nalam, Roopa L.; Clementi, Caterina; Franco, Heather L.; DeMayo, Francesco J.; Lyons, Karen M.; Pangas, Stephanie A.; Matzuk, Martin M.

    2010-01-01

    Bone morphogenetic proteins (BMPs) have diverse roles in development and reproduction. Although several BMPs are produced by oocytes, thecal cells, and granulosa cells of developing follicles, the in vivo functions of most of these ligands are unknown. BMP signals are transduced by multiple type I and type II TGFβ family receptors, and of the type I receptors, BMP receptor 1A (BMPR1A) and BMP receptor 1B (BMPR1B) are known to be expressed in rodent granulosa cells. Female mice homozygous null for Bmpr1b are sterile due to compromised cumulus expansion, but the function of BMPR1A in the ovary is unknown. To further decipher a role for BMP signaling in mouse granulosa cells, we deleted Bmpr1a in the granulosa cells of the ovary and found Bmpr1a conditional knockout females to be subfertile with reduced spontaneous ovulation. To explore the redundant functions of BMP receptor signaling in the ovary, we generated Bmpr1a Bmpr1b double-mutant mice, which developed granulosa cell tumors that have evidence of increased TGFβ and hedgehog signaling. Thus, similar to SMAD1 and SMAD5, which have redundant roles in suppressing granulosa cell tumor development in mice, two type I BMP receptors, BMPR1A and BMPR1B, function together to prevent ovarian tumorigenesis. These studies support a role for a functional BMP signaling axis as a tumor suppressor pathway in the ovary, with BMPR1A and BMPR1B acting downstream of BMP ligands and upstream of BMP receptor SMADs. PMID:20363875

  10. Genetic and genomic dissection of Prolactin revealed potential association with milk production traits in riverine buffalo.

    Science.gov (United States)

    Nadeem, A; Maryam, J

    2016-08-01

    Milk yield and quality has been a major selection criterion for genetic improvement in livestock species. Role of Prolactin gene in determining milk quality in terms of protein profile, lactose, lipids and other imperative macromolecules is very important. In this context, genetic profiling of Prolactin gene in riverine buffalo of Pakistan was performed and potential genetic markers were identified illustrating worth of this gene in marker-assisted selection of superior dairy buffaloes. Series of wet and dry lab experimentation was performed starting with genomic DNA isolation from true to breed representatives of indigenous river buffalo (Nili-Ravi). After amplification of coding regions of Prolactin gene, products were eluted and sequenced by Sanger's chain termination method and aligned to get variations in genomic region. A total of 15 novel variations were identified and analyzed statistically for their significance at population level, haplotypes were constructed, and association was estimated. Phylogenetic analysis was performed to evaluate the rate of evolution for Prolactin gene in various mammalian species. Lastly, biological networking for this molecule was predicted to get the bigger pictorial of its functional machinery. Pathway analysis was performed to find its physiological mode of action in milk synthesis. This is a first report toward complete genetic screening of Prolactin gene in Pakistani buffaloes. Results of this study not only provide an insight for potential role of Prolactin gene in milk-producing abilities of buffalo but also suggest new directions for exploration of more genes that may have promising role to enhance future milk production capabilities of river buffalo breeds of Asian region through marker-assisted selection.

  11. Nascent bipolar outflows associated with the first hydrostatic core candidates Barnard 1b-N and 1b-S

    CERN Document Server

    Gerin, M; Fuente, A; Cernicharo, J; Commerçon, B; Marcelino, N

    2015-01-01

    In the theory of star formation, the first hydrostatic core (FHSC) phase is a critical step in which a condensed object emerges from a prestellar core. This step lasts about one thousand years, a very short time compared with the lifetime of prestellar cores, and therefore is hard to detect unambiguously. We present IRAM Plateau de Bure observations of the Barnard 1b dense molecular core, combining detections of H2CO and CH3OH spectral lines and dust continuum at 2.3" resolution (~ 500 AU). The two compact cores B1b-N and B1b-S are detected in the dust continuum at 2mm, with fluxes that agree with their spectral energy distribution. Molecular outflows associated with both cores are detected. They are inclined relative to the direction of the magnetic field, in agreement with predictions of collapse in turbulent and magnetized gas with a ratio of mass to magnetic flux somewhat higher than the critical value, \\mu ~ 2 - 7. The outflow associated with B1b-S presents sharp spatial structures, with ejection velocit...

  12. Does prolactin mediate parental and life-history decisions in response to environmental conditions in birds? A review.

    Science.gov (United States)

    Angelier, Frédéric; Wingfield, John C; Tartu, Sabrina; Chastel, Olivier

    2016-01-01

    This article is part of a Special Issue "Parental Care". In vertebrates, adjustments of physiology and behavior to environmental changes are often mediated by central physiological mechanisms, and more specifically by hormonal mechanisms. As a consequence, these mechanisms are thought to orchestrate life-history decisions in wild vertebrates. For instance, investigating the hormonal regulation of parental behavior is relevant to evaluate how parents modulate their effort according to specific environmental conditions. Surprisingly and despite being classically known as the 'parental hormone', prolactin has been overlooked in birds relative to this context. Our aim is to review evidence that changes in prolactin levels can mediate, at least to some extent, the response of breeding birds to environmental conditions. To do so, we first examine current evidence and limits for the role of prolactin in mediating parental behavior in birds. Second, we emphasize the influence of environmental conditions and stressors on circulating prolactin levels. In addition, we review to what extent prolactin levels are a reliable predictor of breeding success in wild birds. By linking environmental conditions, prolactin regulation, parental behavior, and breeding success, we highlight the potential role of this hormone in mediating parental decisions in birds. Finally, we also review the potential role of prolactin in mediating other life history decisions such as clutch size, re-nesting, and the timing of molt. By evaluating the influence of stressors on circulating prolactin levels during these other life-history decisions, we also raise new hypotheses regarding the potential of the prolactin stress response to regulate the orchestration of the annual cycle when environmental changes occur. To sum up, we show in this review that prolactin regulation has a strong potential to allow ecological physiologists to better understand how individuals adjust their life-history decisions

  13. Modulations of prolactin and growth hormone gene expression and chromatin structure in cultured rat pituitary cells.

    OpenAIRE

    Levy-Wilson, B

    1983-01-01

    I have measured the effect of hormones and other regulatory factors present in the serum component of the culture medium on the levels of growth hormone and prolactin mRNAs in rat pituitary (GH4) cells. Hybridization of cytoplasmic RNA with growth hormone or prolactin cDNA clones indicate that serum depletion reduces significantly the amount of these two mRNAs. The localization of these two genes in chromatin was also analysed using micrococcal nuclease as a probe. At intermediate levels of d...

  14. 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.

  15. Prolactin suppresses malonyl-CoA concentration in human adipose tissue

    DEFF Research Database (Denmark)

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

    2009-01-01

    +/-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...... as a consequence of suppressed malonyl-CoA concentration in parallel with decreased GLUT-4 expression. In the lactating woman, this regulation in adipose tissue may enhance the provision of nutrients for the infant instead of nutrients being stored in adipose tissue. In hyperprolactinemic individuals, a suppressed...

  16. Direct proteolytic cleavage of NLRP1B is necessary and sufficient for inflammasome activation by anthrax lethal factor.

    Directory of Open Access Journals (Sweden)

    Joseph Chavarría-Smith

    Full Text Available Inflammasomes are multimeric protein complexes that respond to infection by recruitment and activation of the Caspase-1 (CASP1 protease. Activated CASP1 initiates immune defense by processing inflammatory cytokines and by causing a rapid and lytic cell death called pyroptosis. Inflammasome formation is orchestrated by members of the nucleotide-binding domain and leucine-rich repeat (NLR or AIM2-like receptor (ALR protein families. Certain NLRs and ALRs have been shown to function as direct recep