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Sample records for form 1b prolactin

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

    Science.gov (United States)

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

    2012-05-01

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

  2. 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

  3. On Efficient Numerical Approximation of the Bilinear Form c* A(-1)b

    Czech Academy of Sciences Publication Activity Database

    Strakoš, Z.; Tichý, Petr

    2011-01-01

    Roč. 33, č. 2 (2011), s. 565-587 ISSN 1064-8275 R&D Projects: GA AV ČR IAA100300802 Grant - others:GA ČR(CZ) GA201/09/0917; GA AV ČR(CZ) M100300901 Program:GA Institutional research plan: CEZ:AV0Z10300504 Keywords : bilinear forms * scattering amplitude * method of moments * Krylov subspace methods * conjugate gradient method * biconjugate gradient method * Lanczos algorithm * Arnoldi algorithm * Gauss-Christoffel quadrature * model reduction Subject RIV: BA - General Mathematics Impact factor: 1.569, year: 2011

  4. Prolactins, ch. 11

    International Nuclear Information System (INIS)

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

    1976-01-01

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

  5. Prolactin blood test

    Science.gov (United States)

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

  6. A study of the cytoplasmic expression of a form of human prolactin and of its solubilization and renaturation from bacterial inclusion bodies

    International Nuclear Information System (INIS)

    Affonso, Regina

    2000-01-01

    Different vector elements, that can determine a high expression level of a form of human prolactin (taghPrl) in bacterial cytoplasm, were studied. Expression conditions were first optimized for a reference vector, which was used to transform different strains of E. coli: HB2151, RRI and RB791. The highest expression level (113 ±16 μg/mL.A 600 ) was obtained in HB2151, after activation with only 0.1 mM IPTG. At this point the influence of the transcription terminator (g32 from bacteriophage T4), of the translation enhancer (g10 from bacteriophage T7), of the promoter (λP L or tac) and of the antibiotic resistance gene (amp r or kan r ) were studied. The first three elements did not show any significant influence, at least in our systems. On the contrary, the analysis of the influence of amp r and kan r genes showed, unexpectedly, that the presence of the last one provides an approximately 5-fold higher expression for taghPrl in E. coli cytoplasm. Finally, an appropriate extraction, solubilization, renaturation and purification process, able to provide a monomeric form of taghPrl, was studied. A method utilizing urea and mercaptoethanol as solubilizing agents and a dialysis as a renaturation procedure, provided with some modifications, one of the highest yields ever reported in the literature: 35.4 ± 4.5% of total recovery. Moreover, the biological activity of the taghPrl obtained, when tested in the Nb2 cell proliferation assay, was of the same order of that shown by the International Standard of human prolactin of pituitary origin. These data show that the cytoplasmic expression system here described, which can provide an expression efficiency 50-100 - fold higher than the periplasmic expression, can represent a valid alternative for the production of this and of other hormones of pharmaceutical interest and grade. (author)

  7. A Rare Form of Guillan Barre Syndrome: A Child Diagnosed with Anti-GD1a and Anti-GD1b Positive Pharyngeal-Cervical-Brachial Variant

    OpenAIRE

    Uysalol, Metin; Tatlı, Burak; Uzel, Nedret; Çıtak, Agop; Aygün, Erhan; Kayaoğlu, Semra

    2013-01-01

    Background: Pharyngeal-cervical-brachial (PCB) variant is a rare form of Guillan-Barre Syndrome (GBS). Antibodies against other membrane proteins like GM1b and GD1a have been found only in a small number of patients with Guillan Barre syndrome variant. Case Report: Here, we report a 5.5 year-old boy diagnosed early with positive GD1a and GD1b gangliosides of Guillan-Barre syndrome pharyngeal cervical-Brachial variant, who improved and recovered fully in a short period. This is in co...

  8. A Rare Form of Guillan Barre Syndrome: A Child Diagnosed with Anti-GD1a and Anti-GD1b Positive Pharyngeal-Cervical-Brachial Variant

    OpenAIRE

    Uysalol, Metin; Tatlı, Burak; Uzel, Nedret; Çıtak, Agop; Aygün, Erhan; Kayaoğlu, Semra

    2014-01-01

    Background: Pharyngeal-cervical-brachial (PCB) variant is a rare form of Guillan-Barre Syndrome (GBS). Antibodies against other membrane proteins like GM1b and GD1a have been found only in a small number of patients with Guillan Barre syndrome variant. Case Report: Here, we report a 5.5 year-old boy diagnosed early with positive GD1a and GD1b gangliosides of Guillan-Barre syndrome pharyngeal cervical-Brachial variant, who improved and recovered fully in a short period. This is in cont...

  9. In vitro conditions modify immunoassayability of bovine pituitary prolactin and growth hormone: insights into their secretory granule storage forms

    International Nuclear Information System (INIS)

    Lorenson, M.Y.

    1985-01-01

    The amount of immunoassayable intracellular bovine (b) PRL and GH varies depending on treatment conditions. The present studies were designed to characterize the mechanisms involved and to compare immunoassayability of both hormones under similar conditions. Pituitary homogenate and secretory granule hormones displayed both time- and temperature-dependent increases when incubated at pH 10.5 with reduced glutathione. Changes in immunoassayability seem to reflect conversion from poorly immunoactive tissue hormone oligomers to monomeric hormone. The data indicate that oligomeric bPRL is stabilized primarily by intermolecular disulfide bonds, although it is also susceptible to urea, SDS, and EDTA; granule thiols may also influence the conversion to monomer. The storage form of bGH appears to be stabilized differently. Maneuvers demonstrated in these studies to influence immunoassayability correlate very well with their previously established effects on hormone release and secretion, strengthening the likelihood that a functional link exists between assayability and secretion

  10. Clinical indications of prolactin radioimmunoassay

    International Nuclear Information System (INIS)

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

    1980-01-01

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

  11. Serum prolactin revisited

    DEFF Research Database (Denmark)

    Overgaard, Martin; Pedersen, Susanne Møller

    2017-01-01

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

  12. Prolactin induces adrenal hypertrophy

    Directory of Open Access Journals (Sweden)

    E.J. Silva

    2004-02-01

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

  13. Prolactin promotes breast cancer cell migration through actin cytoskeleton remodeling

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    Priscilla Ludovico da Silva

    2015-12-01

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

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  15. Survey of familial glaucoma shows a high incidence of cytochrome P450, family 1, subfamily B, polypeptide 1 (CYP1B1) mutations in non-consanguineous congenital forms in a Spanish population

    Science.gov (United States)

    Millá, Elena; Mañé, Begoña; Duch, Susana; Hernan, Imma; Borràs, Emma; Planas, Ester; Dias, Miguel de Sousa; Carballo, Miguel

    2013-01-01

    Purpose To identify myocilin (MYOC) and cytochrome P450, family 1, subfamily B, polypeptide 1 (CYP1B1) mutations in a Spanish population with different clinical forms of familial glaucoma or ocular hypertension (OHT). Methods Index patients from 226 families participated in this study. Patients were diagnosed with familial glaucoma or OHT by complete ophthalmologic examination. Screening for MYOC mutations was performed in 207 index patients: 96 with adult-onset primary open-angle glaucoma (POAG), 21 with primary congenital glaucoma (PCG), 18 with juvenile-onset open-angle glaucoma (JOAG), five with Axenfeld-Rieger syndrome (ARS), and 67 with other types of glaucoma. One hundred two of the families (including all those in whom a MYOC mutation was detected) were also screened for CYP1B1 mutations: 45 POAG, 25 PCG, 21 JOAG, four ARS, and seven others. Results We examined 292 individuals (patients and relatives) with a positive family history of glaucoma or OHT. We identified two novel MYOC variants, p.Lys39Arg and p.Glu218Lys, in two families with POAG, and six previously reported MYOC mutations in seven families with POAG (four), JOAG (one), PCG (one), and normotensive glaucoma (one). CYP1B1 mutations were found in 16 index patients with PCG (nine), POAG (three), JOAG (two), and ARS (two). Conclusions The high percentage (9/25=36%) of mutations in CYP1B1 found in non-consanguineous patients with congenital glaucoma mandates genetic testing. However, the percentage of mutations (9/207=4.4%) in MYOC associated with glaucoma is relatively low in our population. The variable phenotype expression of glaucoma, even in families, cannot be explained with a digenic mechanism between MYOC and CYP1B1. PMID:23922489

  16. Serum prolactin level in patients taking olanzapine

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    Diganta Das

    2015-01-01

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

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

    NARCIS (Netherlands)

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

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

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

    International Nuclear Information System (INIS)

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

    2011-01-01

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

  19. 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.

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Jimena Ferraris

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

  2. 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.

  3. 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 chronic ... severe, malignant osteopetrosis (an inherited bone disease). Interferon gamma-1b is in a class of medications called ...

  4. Histaminergic regulation of prolactin secretion

    DEFF Research Database (Denmark)

    Knigge, U P

    1990-01-01

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

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

    Science.gov (United States)

    Anuradha; Krishna, Amitabh

    2017-07-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Fernanda das Chagas Angelo Mendes Tenorio

    2015-06-01

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

  10. Prolactin secretion: the impact of dynamic studies

    International Nuclear Information System (INIS)

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

    1975-01-01

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

  11. Obtention of antibodies anti prolactin from human prolactin of national production

    International Nuclear Information System (INIS)

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

    1996-01-01

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

  12. 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.

  13. Synthesis of human prolactin in Chinese hamster ovary (CHO) cells

    International Nuclear Information System (INIS)

    Soares, Carlos Roberto Jorge

    2000-01-01

    Three different eukaryotic expression vectors, based on the same selectable gene marker (dhfr), have been used for dhf- CHO cells transfection to rapidly isolate stable cell lines capable of secreting high levels of recombinant human prolactin (rec-hPRL). Two vectors, one codifying a human prolactin (p658-hPRL) and the other a tag-prolactin (p658-tagPRL), contain the complete hepatitis B virus-X (HBV-X) gene coding for a viral transactivator and a sequence derived from the granulocyte-macrophage colony-stimulating factor (GM-CSF) that mediates selective dhfr mRNA degradation. These vectors have the advantage of rapidly obtaining stable cell lines without methotrexate amplification. The highest secretion obtained by these vectors was of approximately 10 μg hPRU10 6 cells/day. The other vector (pEDdc-hPRL) is based on a dicistronic expression system, containing an internal ribosome entry site isolated from the encephalomyocarditis (EMC) virus. This vector before amplification provided secretion levels at least 10 fold lower than that obtained with the other two vectors. However, after three steps of methotrexate amplification, it provided some clones able to secrete up to 30 μg hPRU10 6 cells/day. This is the first report describing the production and purification of rec-hPRL from CHO cells, obtaining secretion levels with both vectors higher than those reported so far for this hormone in other eukaryotic systems. CHO-derived rec-hPRL contained approximately 10 % of the glycosylated form, a value that is consistent with results reported for hPRL purified from the pituitary or from transformed murine C-127 cells. CHO-derived rec-hPRL was purified with good yield, obtaining also a good resolution between non-glycosylated and glycosylated prolactin. The latter, when its potency was determined via an in vitro bioassay, presented a 47 % lower bioactivity. A qualitative and quantitative analysis of these forms was also possible thanks to the setting up of a reversed

  14. Role of Mammary Prolactin in Carcinogenesis

    Science.gov (United States)

    1998-10-01

    lactating rats (167) and dairy kines tested, IL-4 was the most potent inhibitor of myome- cows (174) by bromocriptine did not lower immunoreactive trial...of prolactin in dairy cows during lactogenesis. J Dairy 151. Chapitis J, Riddick DH, Betz LM, Brumsted JR, Gibson M, Prior Sci 70:2241-2253 JC, Gout...factors, insulin (30) and EGF (31) stim- ing the presence of functional postreceptor signaling mech- ulate, whereas transforming growth factor-P

  15. Simultaneous radioimmunoassay for luteinizing hormone and prolactin

    International Nuclear Information System (INIS)

    Steele, M.K.; Deschepper, C.F.

    1985-01-01

    A combined radioimmunoassay (RIA) for the measurement of the anterior pituitary proteins luteinizing hormone (LH) and prolactin (PRL) is described and compared with individual RIAs for these hormones. The standard curves and the sample values for LH and PRL were identical when determined in a combined or in an individual RIA. This technique may prove useful to a number of laboratories where it is desirable to determine levels of more than one hormone in limited sample volumes

  16. Maintenance of prolactin receptors in human breast cancer

    International Nuclear Information System (INIS)

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

    1981-01-01

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

  17. Enhanced prolactin levels in opium smokers.

    Science.gov (United States)

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

    2005-12-01

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

  18. Development of radioimmunoassay for prolactin binding protein

    Energy Technology Data Exchange (ETDEWEB)

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

    1982-01-01

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

  19. Interactions between prolactin and kisspeptin to control reproduction.

    Science.gov (United States)

    Donato, Jose; Frazão, Renata

    2016-01-01

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

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

    International Nuclear Information System (INIS)

    Caso, R.; Arranz, C.

    1996-01-01

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

  1. Elephant Endotheliotropic Herpesviruses EEHV1A, EEHV1B, and EEHV2 from Cases of Hemorrhagic Disease Are Highly Diverged from Other Mammalian Herpesviruses and May Form a New Subfamily

    Science.gov (United States)

    Richman, Laura K.; Zong, Jian-Chao; Latimer, Erin M.; Lock, Justin; Fleischer, Robert C.; Heaggans, Sarah Y.

    2014-01-01

    ABSTRACT A family of novel endotheliotropic herpesviruses (EEHVs) assigned to the genus Proboscivirus have been identified as the cause of fatal hemorrhagic disease in 70 young Asian elephants worldwide. Although EEHV cannot be grown in cell culture, we have determined a total of 378 kb of viral genomic DNA sequence directly from clinical tissue samples from six lethal cases and two survivors. Overall, the data obtained encompass 57 genes, including orthologues of 32 core genes common to all herpesviruses, 14 genes found in some other herpesviruses, plus 10 novel genes, including a single large putative transcriptional regulatory protein (ORF-L). On the basis of differences in gene content and organization plus phylogenetic analyses of conserved core proteins that have just 20% to 50% or less identity to orthologues in other herpesviruses, we propose that EEHV1A, EEHV1B, and EEHV2 could be considered a new Deltaherpesvirinae subfamily of mammalian herpesviruses that evolved as an intermediate branch between the Betaherpesvirinae and Gammaherpesvirinae. Unlike cytomegaloviruses, EEHV genomes encode ribonucleotide kinase B subunit (RRB), thymidine kinase (TK), and UL9-like origin binding protein (OBP) proteins and have an alphaherpesvirus-like dyad symmetry Ori-Lyt domain. They also differ from all known betaherpesviruses by having a 40-kb large-scale inversion of core gene blocks I, II, and III. EEHV1 and EEHV2 DNA differ uniformly by more than 25%, but EEHV1 clusters into two major subgroups designated EEHV1A and EEHV1B with ancient partially chimeric features. Whereas large segments are nearly identical, three nonadjacent loci totaling 15 kb diverge by between 21 and 37%. One strain of EEHV1B analyzed is interpreted to be a modern partial recombinant with EEHV1A. IMPORTANCE Asian elephants are an endangered species whose survival is under extreme pressure in wild range countries and whose captive breeding populations in zoos are not self-sustaining. In 1999, a

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

    International Nuclear Information System (INIS)

    Massa, J.S.

    1986-01-01

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

  3. 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

  4. Sex differences in the hypothalamic control of prolactin secretion

    International Nuclear Information System (INIS)

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

    2001-01-01

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

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

    Science.gov (United States)

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

    2014-05-30

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

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

    African Journals Online (AJOL)

    p2492989

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

  7. Mammalian Prolactin – An Ancient But Still A Mysterious Hormone

    Indian Academy of Sciences (India)

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

  8. 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.

  9. Development and characterization of a homologous radioimmunoassay for equine prolactin

    International Nuclear Information System (INIS)

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

    1984-01-01

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

  10. Agnus castus extracts inhibit prolactin secretion of rat pituitary cells.

    Science.gov (United States)

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

    1993-05-01

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

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

    Science.gov (United States)

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

    1986-03-01

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

  12. 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.

  13. Polymorphism of the prolactin gene (PRL) and its relationship with ...

    African Journals Online (AJOL)

    enoh

    2012-04-10

    Apr 10, 2012 ... prolactin gene (PRL), associated with milk production and quality (Brymet et al., 2005; ... synthesis and secretion of proteins, lactose, lipids, and other important ..... genotype AB in Black Pied cattle affected milk, fat and protein ...

  14. 21 CFR 862.1625 - Prolactin (lactogen) test system.

    Science.gov (United States)

    2010-04-01

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

  15. Prolactin deficiency, obesity, and enlarged testes--a new syndrome?

    Science.gov (United States)

    Roitman, A; Assa, S; Kauli, R; Laron, Z

    1980-01-01

    A 4-year-old boy is described who was obese and slightly mentally retarded. His testes were enlarged. The only endocrine disorder present was a failure to increase plasma prolactin after stimulation. Images Figure PMID:7436524

  16. Cyclical Changes in Prolactin Levels among Infertile Women ...

    African Journals Online (AJOL)

    Michael Horsfall

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

  17. Prolactin, cortisol and thyroxine levels and the premature infant

    African Journals Online (AJOL)

    1983-04-16

    Apr 16, 1983 ... and the premature infant ... values in cord and maternal plasma to fetal age and weight and to the incidence of hyaline membrane disease (HMD) was .... thyroxine and prolactin values with an increase in weight has also.

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

    OpenAIRE

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

    2015-01-01

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

  19. 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

  20. 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.21 Section 1b.21 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION... shall be treated as non-public by the Commission and its staff, consistent with the provisions of...

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

    International Nuclear Information System (INIS)

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

    1978-01-01

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

  2. 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.

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

    Science.gov (United States)

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

    2007-08-01

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

  4. Serum prolactin profiles of normal human conception cycles

    Energy Technology Data Exchange (ETDEWEB)

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

    1984-06-01

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

  5. Processing TES Level-1B Data

    Science.gov (United States)

    DeBaca, Richard C.; Sarkissian, Edwin; Madatyan, Mariyetta; Shepard, Douglas; Gluck, Scott; Apolinski, Mark; McDuffie, James; Tremblay, Dennis

    2006-01-01

    TES L1B Subsystem is a computer program that performs several functions for the Tropospheric Emission Spectrometer (TES). The term "L1B" (an abbreviation of "level 1B"), refers to data, specific to the TES, on radiometric calibrated spectral radiances and their corresponding noise equivalent spectral radiances (NESRs), plus ancillary geolocation, quality, and engineering data. The functions performed by TES L1B Subsystem include shear analysis, monitoring of signal levels, detection of ice build-up, and phase correction and radiometric and spectral calibration of TES target data. Also, the program computes NESRs for target spectra, writes scientific TES level-1B data to hierarchical- data-format (HDF) files for public distribution, computes brightness temperatures, and quantifies interpixel signal variability for the purpose of first-order cloud and heterogeneous land screening by the level-2 software summarized in the immediately following article. This program uses an in-house-developed algorithm, called "NUSRT," to correct instrument line-shape factors.

  6. Independent System Calibration of Sentinel-1B

    Directory of Open Access Journals (Sweden)

    Marco Schwerdt

    2017-05-01

    Full Text Available Sentinel-1B is the second of two C-Band Synthetic Aperture Radar (SAR satellites of the Sentinel-1 mission, launched in April 2016—two years after the launch of the first satellite, Sentinel-1A. In addition to the commissioning of Sentinel-1B executed by the European Space Agency (ESA, an independent system calibration was performed by the German Aerospace Center (DLR on behalf of ESA. Based on an efficient calibration strategy and the different calibration procedures already developed and applied for Sentinel-1A, extensive measurement campaigns were executed by initializing and aligning DLR’s reference targets deployed on the ground. This paper describes the different activities performed by DLR during the Sentinel-1B commissioning phase and presents the results derived from the analysis and the evaluation of a multitude of data takes and measurements.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1978-11-01

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

  8. Polymorphism of the prolactin gene (PRL) and its relationship with ...

    African Journals Online (AJOL)

    The modern dairy cattle breeding strategy in the Mexican tropic is to identify genes or allelic variants that can be incorporated into selection programs such as the prolactin gene (PRL) which is associated with milk production and quality. The aim of this study is to screen an American Swiss population in Chiapas, Mexico, ...

  9. Prolactin and Male Fertility: The Long and Short Feedback Regulation

    Directory of Open Access Journals (Sweden)

    M. K. Gill-Sharma

    2009-01-01

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

  10. Prolactin, cortisol and thyroxine levels and the premature infant ...

    African Journals Online (AJOL)

    The relationship of prolactin, cortisol and thyroxine values in cord and maternal plasma to fetal age and weight and to the incidence of hyaline membrane disease (HMD) was investigated in 80 neonates of whom 40 were born at more than 37 weeks' gestation. Of the 40 born at less than 36 weeks 11 developed HMD.

  11. Prolactin-releasing peptide: a new tool for obesity treatment

    Czech Academy of Sciences Publication Activity Database

    Kuneš, Jaroslav; Pražienková, V.; Popelová, A.; Mikulášková, Barbora; Zemenová, J.; Maletínská, L.

    2016-01-01

    Roč. 230, č. 2 (2016), R51-R58 ISSN 0022-0795 R&D Projects: GA ČR(CZ) GA15-08679S Institutional support: RVO:67985823 Keywords : prolactin-releasing peptide * lipidization * obesity * GPR10 * anorexigenic * mice Subject RIV: ED - Physiology Impact factor: 4.706, year: 2016

  12. Prolactin-releasing peptide: a new tool for obesity treatment

    Czech Academy of Sciences Publication Activity Database

    Kuneš, Jaroslav; Pražienková, Veronika; Popelová, Andrea; Mikulášková, Barbora; Zemenová, Jana; Maletínská, Lenka

    2016-01-01

    Roč. 230, č. 2 (2016), R51-R58 ISSN 0022-0795 R&D Projects: GA ČR(CZ) GA15-08679S Institutional support: RVO:61388963 Keywords : prolactin-releasing peptide * lipidization * obesity * GPR10 * anorexigenic * mice Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 4.706, year: 2016

  13. A pigeon crop sac radioreceptor assay for prolactin

    International Nuclear Information System (INIS)

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

    1978-01-01

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

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

    Science.gov (United States)

    Hutchison, R E

    1975-10-01

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

  15. Human breast cancer: concerted role of diet, prolactin and adrenal C19-delta 5-steroids in tumorigenesis.

    Science.gov (United States)

    Adams, J B

    1992-04-01

    The low incidence of breast cancer in Japan disappears within 2 generations in migrant Japanese in the USA. This is of fundamental importance if we are to understand, and perhaps reverse, the high rate seen in Western countries. Diet is the most likely factor involved, and a review of the topic of diet, body mass index, and gain in adult body mass, supports a relationship between these factors and breast-cancer risk in post-menopausal, but not pre-menopausal, women. A direct link between nutritional factors and secretion of the hormones prolactin and dehydroepiandrosterone sulfate is proposed. An estrogen 5-androstene-3 beta, 17 beta-diol is formed peripherally from the latter steroid, and in Western women attains a blood concentration at which it is biologically active. Thus diet/fat provides factors, viz., fatty acids, prolactin and estrogen, which in concerted fashion provide a milieu conducive to mammary tumorigenesis.

  16. 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.

  17. Deletion of SNURF/SNRPN U1B and U1B* upstream exons in a ...

    Indian Academy of Sciences (India)

    RESEARCH ARTICLE. Deletion of SNURF/SNRPN U1B and U1B* upstream exons in a child ... whereby genes are expressed in a parent-of-origin dependent manner. One of the ... lity, neurodevelopmental delay, features of attention deficit hyperactivity .... Received 16 December 2015; accepted 8 January 2016. Unedited ...

  18. 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.)

  19. ESA Swarm Mission - Level 1b Products

    Science.gov (United States)

    Tøffner-Clausen, Lars; Floberghagen, Rune; Mecozzi, Riccardo; Menard, Yvon

    2014-05-01

    Swarm, a three-satellite constellation to study the dynamics of the Earth's magnetic field and its interactions with the Earth system, has been launched in November 2013. The objective of the Swarm mission is to provide the best ever survey of the geomagnetic field and its temporal evolution, which will bring new insights into the Earth system by improving our understanding of the Earth's interior and environment. The Level 1b Products of the Swarm mission contain time-series of the quality screened, calibrated, corrected, and fully geo-localized measurements of the magnetic field intensity, the magnetic field vector (provided in both instrument and Earth-fixed frames), the plasma density, temperature, and velocity. Additionally, quality screened and pre-calibrated measurements of the nongravitational accelerations are provided. Geo-localization is performed by 24- channel GPS receivers and by means of unique, three head Advanced Stellar Compasses for high-precision satellite attitude information. The Swarm Level 1b data will be provided in daily products separately for each of the three Swarm spacecrafts. This poster will present detailed lists of the contents of the Swarm Level 1b Products and brief descriptions of the processing algorithms used in the generation of these data.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1996-07-01

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

  1. 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.

  2. Prolactin-inducible proteins in human breast cancer cells

    International Nuclear Information System (INIS)

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

    1985-01-01

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

  3. The Influence of Phytotherapy on Prolactin Level in Macroprolactinoma Patients

    OpenAIRE

    Trogrlić, Ivo; Trogrlić, Dragan; Trogrlić, Zoran

    2011-01-01

    The study aims at demonstrating the efficiency of phytotherapy in regulation of prolactin levels in patients diagnosed with pituitary macroprolactinoma. The study made use of workup outcomes submitted by treating healthcare facilities where the patients were first diagnosed with macroprolactinomas based on diagnostic imaging (MRI and/or CT), laboratory workup, and hormone status estimation. The data in reference served as the baseline for a comparative follow-up of phytotherapeutic efficiency...

  4. Prolactin suppresses malonyl-CoA concentration in human adipose tissue

    DEFF Research Database (Denmark)

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

    2009-01-01

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

  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. The importance of prolactin for lactation in the ewe

    International Nuclear Information System (INIS)

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

    1978-01-01

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

  7. Importance of prolactin for lactation in the ewe

    Energy Technology Data Exchange (ETDEWEB)

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

    1978-12-01

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

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

    International Nuclear Information System (INIS)

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

    1980-01-01

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

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

    International Nuclear Information System (INIS)

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

    1994-01-01

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

  10. 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.

  11. Night shift work and prolactin as a breast cancer risk factor

    Directory of Open Access Journals (Sweden)

    Agnieszka Bukowska

    2013-04-01

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

  12. Gfi1b controls integrin signaling-dependent cytoskeleton dynamics and organization in megakaryocytes.

    Science.gov (United States)

    Beauchemin, Hugues; Shooshtarizadeh, Peiman; Vadnais, Charles; Vassen, Lothar; Pastore, Yves D; Möröy, Tarik

    2017-03-01

    Mutations in GFI1B are associated with inherited bleeding disorders called GFI1B -related thrombocytopenias. We show here that mice with a megakaryocyte-specific Gfi1b deletion exhibit a macrothrombocytopenic phenotype along a megakaryocytic dysplasia reminiscent of GFI1B -related thrombocytopenia. GFI1B deficiency increases megakaryocyte proliferation and affects their ploidy, but also abrogates their responsiveness towards integrin signaling and their ability to spread and reorganize their cytoskeleton. Gfi1b -null megakaryocytes are also unable to form proplatelets, a process independent of integrin signaling. GFI1B-deficient megakaryocytes exhibit aberrant expression of several components of both the actin and microtubule cytoskeleton, with a dramatic reduction of α-tubulin. Inhibition of FAK or ROCK, both important for actin cytoskeleton organization and integrin signaling, only partially restored their response to integrin ligands, but the inhibition of PAK, a regulator of the actin cytoskeleton, completely rescued the responsiveness of Gfi1b -null megakaryocytes to ligands, but not their ability to form proplatelets. We conclude that Gfi1b controls major functions of megakaryocytes such as integrin-dependent cytoskeleton organization, spreading and migration through the regulation of PAK activity whereas the proplatelet formation defect in GFI1B-deficient megakaryocytes is due, at least partially, to an insufficient α-tubulin content. Copyright© Ferrata Storti Foundation.

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

    Science.gov (United States)

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

    1992-02-01

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

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

    International Nuclear Information System (INIS)

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

    1989-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1989-06-01

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

  16. 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.

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

    Directory of Open Access Journals (Sweden)

    Charles T Snowdon

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

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

    Science.gov (United States)

    Curlewis, J D

    1992-01-01

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

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

    International Nuclear Information System (INIS)

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

    1998-01-01

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

  20. Pituitary Macroprolactinoma with Mildly Elevated Serum Prolactin: Hook Effect

    Directory of Open Access Journals (Sweden)

    Mahnaz Pejman-Sani

    2018-04-01

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

  1. Evaluation of the human prolactin of National Production for use in radioimmunoassay (RIA); Evaluacion de la prolactina humana de produccion nacional para su empleo en radioimmunoanalisis (RIA)

    Energy Technology Data Exchange (ETDEWEB)

    Caso, R [Centro de Isotopos, La Habana (Cuba); Arranz, C [Instituto Nacional de Endocrinologia, La Habana (Cuba)

    1996-07-01

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

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

    Directory of Open Access Journals (Sweden)

    G FAGHIHI

    2002-03-01

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

  3. 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.

    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,

  4. 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,

  5. 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.

  6. Jumonji/Arid1b (Jarid1b) protein modulates human esophageal cancer cell growth

    Science.gov (United States)

    KANO, YOSHIHIRO; KONNO, MASAMITSU; OHTA, KATSUYA; HARAGUCHI, NAOTSUGU; NISHIKAWA, SHIMPEI; KAGAWA, YOSHINORI; HAMABE, ATSUSHI; HASEGAWA, SHINICHIRO; OGAWA, HISATAKA; FUKUSUMI, TAKAHITO; NOGUCHI, YUKO; OZAKI, MIYUKI; KUDO, TOSHIHIRO; SAKAI, DAISUKE; SATOH, TAROH; ISHII, MASARU; MIZOHATA, EIICHI; INOUE, TAKESHI; MORI, MASAKI; DOKI, YUICHIRO; ISHII, HIDESHI

    2013-01-01

    Although esophageal cancer is highly heterogeneous and the involvement of epigenetic regulation of cancer stem cells is highly suspected, the biological significance of epigenetically modified molecules that regulate different subpopulations remains to be firmly established. Using esophageal cancer cells, we investigated the functional roles of the H3K4 demethylase Jumonji/Arid1b (Jarid1b) (Kdm5b/Plu-1/Rbp2-h1), an epigenetic factor that is required for continuous cell growth in melanoma. JARID1B knockdown resulted in the suppression of esophageal cancer cell growth, sphere formation and invasion ability and was associated with loss of epithelial marker expression. However, these inhibitory effects observed on tumor formation were reverted subsequent to subcutaneous inoculation of these cells into immune-deficient mice. These results indicated that JARID1B plays a role in maintaining cancer stem cells in the esophagus and justifies the rationale for studying the effects of continuous inhibition of this epigenetic factor in esophageal cancer. PMID:24649241

  7. Prolactin cycling and the management of breast-feeding failure.

    Science.gov (United States)

    Weichert, C E

    1980-01-01

    Various studies (Tyson et.al.; Frantz; Aono et.al.) show that cycling of prolactin is critical to the establishment of successful lactation in the first 60 to 80 days postpartum, and that a 2-hour nursing interval is associated with a statistically significant earlier onset of milk production (Salarija et.al.). However, in the patient with a lactational insufficiency, efforts to increase the frequency of nursing more often than every 2 hours may be counterproductive, as experimental evidence shows that prolactin exerts a negative feedback upon itself, and the patient with a breastfeeding problems may experience increased episodes of anxiety and fatigue. The patient with breast milk insufficiency can be managed by ensuring that a sucking stimulus of 30 minutes (15 minutes bilaterally) be present and repeated every 2-3 hours to provide adequate stimulation for prolactin release. Maternal anxiety about milk supply can be relieved by using the Lact-Aid nursing supplementer, a device which provides an additional source of milk to the infant at the breast. Nursing should be carried out in a sheltered situation to provide an uninterrupted sucking stimulus devoid of distraction. The mother should be directed to focus on pleasant associations while nursing to keep her from worrying about whether she will have enough milk. Symptoms of lactational insufficiency can be corrected with proper hormonal regulation. Evaluation of a breastfeeding disorder depends upon a careful physical examination of the breast, preferably to be done prior to and during infant nursing. Observation of infant nursing has not been a standard part of physical examination, although it is critical to making a diagnosis of the problem. The principles of breastfeeding management are illustrated in 3 cases in this chapter. In cases where there is no response to treatment, additional evaluation of the patient's developmental (e.g., adolescent attitude towards the breast) attitude and sexual function history

  8. 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.

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

    Bukowska, Agnieszka; Sobala, Wojciech; Peplonska, Beata

    2015-04-01

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

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

    African Journals Online (AJOL)

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

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

    African Journals Online (AJOL)

    STORAGESEVER

    2009-10-05

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

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

    International Nuclear Information System (INIS)

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

    1977-01-01

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

  14. Submaximal doses of ghrelin do not inhibit gonadotrophin levels but stimulate prolactin secretion in postmenopausal women.

    Science.gov (United States)

    Messini, Christina I; Malandri, Maria; Anifandis, George; Dafopoulos, Konstantinos; Georgoulias, Panagiotis; Sveronis, Georgios; Garas, Antonios; Daponte, Alexandros; Messinis, Ioannis E

    2017-07-01

    An inhibitory effect of ghrelin on gonadotrophin secretion has been reported in normally menstruating women possibly modulated by endogenous oestrogen. The aim of this study was to examine the effect of ghrelin on gonadotrophin and prolactin (PRL) secretion in oestrogen-deprived postmenopausal women. Prospective intervention study. Ten healthy postmenopausal volunteer women were studied during two 15-days periods of oestrogen treatment (A and B) a month apart. Four experiments (Exp) were performed in total, two on day 1 (Exp 1A and Exp 1B) and two on day 15 (Exp 15A and Exp 15B) of the two periods. The women received in Exp 1A and in Exp 15A two iv injections of ghrelin (0.15 μg/kg at time 0 minute and 0.30 μg/kg at time 90 minutes) and in Exp1B and in Exp 15B normal saline (2 mL), respectively. Blood samples were taken at -15, 0, 30, 60, 90, 120, 150 and 180 minutes. After oestrogen treatment, late follicular phase serum oestradiol levels were attained on day 15 of periods A and B. Ghrelin administration did not affect serum levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), whereas it increased significantly those of growth hormone (GH) and PRL. In Exp 15A, serum PRL increment in response to ghrelin (area under the curve, net increment) was significantly greater than in Exp 1A (Pghrelin administration affects neither FSH nor LH levels but stimulates PRL secretion, that is amplified by exogenous oestrogen administration. © 2017 John Wiley & Sons Ltd.

  15. 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

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

    Science.gov (United States)

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

    1989-01-01

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

  17. [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.

  18. Spitzer secondary eclipses of Qatar-1b

    Science.gov (United States)

    Garhart, Emily; Deming, Drake; Mandell, Avi; Knutson, Heather; Fortney, Jonathan J.

    2018-02-01

    Aims: Previous secondary eclipse observations of the hot Jupiter Qatar-1b in the Ks band suggest that it may have an unusually high day side temperature, indicative of minimal heat redistribution. There have also been indications that the orbit may be slightly eccentric, possibly forced by another planet in the system. We investigate the day side temperature and orbital eccentricity using secondary eclipse observations with Spitzer. Methods: We observed the secondary eclipse with Spitzer/IRAC in subarray mode, in both 3.6 and 4.5 μm wavelengths. We used pixel-level decorrelation to correct for Spitzer's intra-pixel sensitivity variations and thereby obtain accurate eclipse depths and central phases. Results: Our 3.6 μm eclipse depth is 0.149 ± 0.051% and the 4.5 μm depth is 0.273 ± 0.049%. Fitting a blackbody planet to our data and two recent Ks band eclipse depths indicates a brightness temperature of 1506 ± 71 K. Comparison to model atmospheres for the planet indicates that its degree of longitudinal heat redistribution is intermediate between fully uniform and day-side only. The day side temperature of the planet is unlikely to be as high (1885 K) as indicated by the ground-based eclipses in the Ks band, unless the planet's emergent spectrum deviates strongly from model atmosphere predictions. The average central phase for our Spitzer eclipses is 0.4984 ± 0.0017, yielding e cos ω = -0.0028 ± 0.0027. Our results are consistent with a circular orbit, and we constrain e cos ω much more strongly than has been possible with previous observations. Tables of the lightcurve data are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/610/A55

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

    International Nuclear Information System (INIS)

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

    1986-01-01

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

  20. Characterization of the C-terminal ER membrane anchor of PTP1B

    International Nuclear Information System (INIS)

    Anderie, Ines; Schulz, Irene; Schmid, Andreas

    2007-01-01

    The tyrosine phosphatase PTP1B is an important regulator of cell function. In living cells PTP1B activity is restricted to the vicinity of the endoplasmic reticulum (ER) by post-translational C-terminal attachment of PTP1B to the ER membrane network. In our study we investigated the membrane anchor of PTP1B by use of EGFP fusion proteins. We demonstrate that the membrane anchor of PTP1B cannot be narrowed down to a unique amino acid sequence with a defined start and stop point but rather is moveable within several amino acids. Removal of up to seven amino acids from the C-terminus, as well as exchange of single amino acids in the putative transmembrane sequence did not influence subcellular localization of PTP1B. With the method of bimolecular fluorescence complementation we could demonstrate dimerization of PTP1B in vivo. Homodimerization was, in contrast to other tail-anchored proteins, not dependent on the membrane anchor. Our data demonstrate that the C-terminal membrane anchor of PTP1B is formed by a combination of a single stretch transmembrane domain (TMD) followed by a tail. TMD and tail length are variable and there are no sequence-specific features. Our data for PTP1B are consistent with a concept that explains the ER membrane anchor of tail-anchored proteins as a physicochemical structure

  1. PTP1B is a negative regulator of interleukin 4–induced STAT6 signaling

    Science.gov (United States)

    Lu, Xiaoqing; Malumbres, Raquel; Shields, Benjamin; Jiang, Xiaoyu; Sarosiek, Kristopher A.; Natkunam, Yasodha

    2008-01-01

    Protein tyrosine phosphatase 1B (PTP1B) is a ubiquitously expressed enzyme shown to negatively regulate multiple tyrosine phosphorylation-dependent signaling pathways. PTP1B can modulate cytokine signaling pathways by dephosphorylating JAK2, TYK2, and STAT5a/b. Herein, we report that phosphorylated STAT6 may serve as a cytoplasmic substrate for PTP1B. Overexpression of PTP1B led to STAT6 dephosphorylation and the suppression of STAT6 transcriptional activity, whereas PTP1B knockdown or deficiency augmented IL-4–induced STAT6 signaling. Pretreatment of these cells with the PTK inhibitor staurosporine led to sustained STAT6 phosphorylation consistent with STAT6 serving as a direct substrate of PTP1B. Furthermore, PTP1B-D181A “substrate-trapping” mutants formed stable complexes with phosphorylated STAT6 in a cellular context and endogenous PTP1B and STAT6 interacted in an interleukin 4 (IL-4)–inducible manner. We delineate a new negative regulatory loop of IL-4–JAK-STAT6 signaling. We demonstrate that IL-4 induces PTP1B mRNA expression in a phosphatidylinositol 3-kinase–dependent manner and enhances PTP1B protein stability to suppress IL-4–induced STAT6 signaling. Finally, we show that PTP1B expression may be preferentially elevated in activated B cell–like diffuse large B-cell lymphomas. These observations identify a novel regulatory loop for the regulation of IL-4–induced STAT6 signaling that may have important implications in both neoplastic and inflammatory processes. PMID:18716132

  2. Caged xanthones displaying protein tyrosine phosphatase 1B (PTP1B) inhibition from Cratoxylum cochinchinense.

    Science.gov (United States)

    Li, Zuo Peng; Lee, Hyeong-Hwan; Uddin, Zia; Song, Yeong Hun; Park, Ki Hun

    2018-08-01

    Four new caged xanthones (1-4) and two known compounds (5, 6) were isolated from the roots of Cratoxylum cochinchinense, a polyphenol rich plant, collected in China. The structures of the isolated compounds (1-6) were characterized by obtaining their detailed spectroscopic data. In particular, compounds 1 and 6 were fully identified by X-ray crystallographic data. The isolated compounds (1-6) were evaluated against protein tyrosine phosphatase 1B (PTP1B), which plays an important role in diabetes, obesity, and cancer. Among these compounds, 3, 4, and 6 displayed significant inhibition with IC 50 values of 76.3, 43.2, and 6.6 µM, respectively. A detailed kinetic study was conducted by determining K m , V max , and the ratio of K ik and K iv , which revealed that all the compounds behaved as competitive inhibitors. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. Suppressed serum prolactin in sinoaortic-denervated rats

    International Nuclear Information System (INIS)

    Alexander, N.; Melmed, S.; Morris, M.

    1987-01-01

    The authors investigated the effect of arterial baroreceptor deafferentation on serum and pituitary prolactin (PRL) and on catecholamines in median eminence (ME) and anterior and posterior pituitaries. Male Wistar rats were sinoaortic denervated (SAD) or sham operated (SO). Three days after surgery serum prolactin, measured by radioimmunoassay, was suppressed in SAD rats, and dopamine (DA) and norepinephrine (NE) concentrations, measured by radioenzymatic or high-performance liquid chromatography electron capture methods, were significantly reduced in ME of SAD rats. Simultaneously, anterior pituitary of SAD rats had significant increases in both catecholamines, whereas posterior pituitary showed no changes. Four hours after surgery serum PRL was also reduced in SAD rats, but no changes in ME catecholamines were found. Mean arterial pressure (MAP) and heart rate were measured before and after injection of bromocriptine in SAD and SO rats 3 days after surgery. Bromocriptine markedly suppressed serum PRL in both groups and reduced MAP from 144 +/- 10 to 84 +/- 5 and from 116 +/- 2 to 99 +/- 3 in SAD and SO rats, respectively; heart rate was reduced in SAD rats. They conclude that the SAD rat is a model of hypertension with suppressed serum PRL and that interruption of arterial baroreceptor nerves suppresses PRL secretion probably by modulating tuberoinfundibular turnover of catecholamines

  4. Geometrical criteria for characterizing open and closed states of WPD-loop in PTP1B

    Science.gov (United States)

    Shinde, Ranajit Nivrutti; Elizabeth Sobhia, M.

    2012-06-01

    Distinctive movement of WPD-loop occurs during the catalysis of phosphotyrosine by protein tyrosine phosphatase 1B (PTP1B). This loop is in the "open" state in apo-form whereas it is catalytically competent in the "closed" state. During the closure of this loop, unique hydrogen bond interactions are formed between different residues of the PTP1B. Present study examines such interactions from the available 118 crystal structures of PTP1B. It gives insights into the five novel hydrogen bonds essentially formed in the "closed" loop structures. Additionally, the study provides distance ranges between the atoms involved in the hydrogen bonds. This information can be used as a geometrical criterion in the characterization of conformational state of the WPD-loop especially in the molecular dynamics simulations.

  5. 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 (pPCR. 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. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2017-08-01

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

  7. IceBridge Atmospheric Chemistry L1B Data

    Data.gov (United States)

    National Aeronautics and Space Administration — The IceBridge Atmospheric Chemistry L1B Data set (ICHEM1B) contains measurements acquired over Antarctica using the AVOCET differential Non-Dispersive Infrared...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1980-05-01

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

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

    Directory of Open Access Journals (Sweden)

    C. D. C. Sanches

    2018-04-01

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

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

    Science.gov (United States)

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

    2000-02-01

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

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

    Science.gov (United States)

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

    1997-01-01

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

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    Janet eAshbury

    2012-12-01

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

  14. Association of neuropeptide Y (NPY, interleukin-1B (IL1B genetic variants and correlation of IL1B transcript levels with vitiligo susceptibility.

    Directory of Open Access Journals (Sweden)

    Naresh C Laddha

    Full Text Available BACKGROUND: Vitiligo is a depigmenting disorder resulting from loss of functional melanocytes in the skin. NPY plays an important role in induction of immune response by acting on a variety of immune cells. NPY synthesis and release is governed by IL1B. Moreover, genetic variability in IL1B is reported to be associated with elevated NPY levels. OBJECTIVES: Aim of the present study was to explore NPY promoter -399T/C (rs16147 and exon2 +1128T/C (rs16139 polymorphisms as well as IL1B promoter -511C/T (rs16944 polymorphism and to correlate IL1B transcript levels with vitiligo. METHODS: PCR-RFLP method was used to genotype NPY -399T/C SNP in 454 patients and 1226 controls; +1128T/C SNP in 575 patients and 1279 controls and IL1B -511C/T SNP in 448 patients and 785 controls from Gujarat. IL1B transcript levels in blood were also assessed in 105 controls and 95 patients using real-time PCR. RESULTS: Genotype and allele frequencies for NPY -399T/C, +1128T/C and IL1B -511C/T SNPs differed significantly (p<0.0001, p<0.0001; p = 0.0161, p = 0.0035 and p<0.0001, p<0.0001 between patients and controls. 'TC' haplotype containing minor alleles of NPY polymorphisms was significantly higher in patients and increased the risk of vitiligo by 2.3 fold (p<0.0001. Transcript levels of IL1B were significantly higher, in patients compared to controls (p = 0.0029, in patients with active than stable vitiligo (p = 0.015, also in female patients than male patients (p = 0.026. Genotype-phenotype correlation showed moderate association of IL1B -511C/T polymorphism with higher IL1B transcript levels. Trend analysis revealed significant difference between patients and controls for IL1B transcript levels with respect to different genotypes. CONCLUSION: Our results suggest that NPY -399T/C, +1128T/C and IL1B -511C/T polymorphisms are associated with vitiligo and IL1B -511C/T SNP influences its transcript levels leading to increased risk for vitiligo in

  15. Antimicrobial activity and self-assembly behavior of antimicrobial peptide chensinin-1b with lipophilic alkyl tails.

    Science.gov (United States)

    Dong, Weibing; Liu, Ziang; Sun, Liying; Wang, Cui; Guan, Yue; Mao, Xiaoman; Shang, Dejing

    2018-04-25

    The threshold hydrophobicity and amphipathic structure of the peptidic chain are important for the biological function of antimicrobial peptides. Chensinin-1b exhibits broad-spectrum bactericidal activity with no hemolytic activity but has almost no anticancer ability against the selected cancer cell lines. In this study, the conjugation of aliphatic acid was designed with different lengths of N-terminal of chensinin-1b, the antimicrobial activity of the resulting lipo-chensinin-1b was examined, in which OA-C1b showed much stronger activity than those of cheninin-1b and the other two lipopeptides. The membrane interaction between the lipo-chensinin-1b and real/mimetic bacterial cell membrane was investigated. Electrostatic interactions between the lipo-chensinin-1b and lipopolysaccharides were detected by isothermal titration calorimetry and the binding affinities were 10.83 μM, 8.77 μM and 7.35 μM for OA-C1b, LA-C1b and PA-C1b, respectively. The antimicrobial activity and membrane interaction ability of the lipo-chensinin-1b followed this order: OA-C1b > chensinin-1b > LA-C1b > PA-C1b. In addition, the lipo-chensinin-1b also exhibited lytic activity against various cancer cells and demonstrated the ability to inhibit LPS-stimulated cytokine release from human U937 cells. The CD spectra indicated that the helical or β-strands contents were existed as the main components in TFE or LPS solution, respectively. The self-assembly behavior was trigged by the solution pH and affected by the length of carbon chain, in which chensinin-1b, OA-C1b, LA-C1b and PA-C1b formed micelles at neutral pH and the micelle size increased for chensinin-1b, OA-C1b and LA-C1b. PA-C1b formed nanofibers in an acidic environment indicated by TEM experiments, and the peptides formed aggregates in an acidic environment and re-dissociated when the pH was adjusted to neutral. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  16. Wilms Tumor 1b defines a wound-specific sheath cell subpopulation associated with notochord repair

    Science.gov (United States)

    Lopez-Baez, Juan Carlos; Zeng, Zhiqiang; Brunsdon, Hannah; Salzano, Angela; Brombin, Alessandro; Wyatt, Cameron; Rybski, Witold; Huitema, Leonie F A; Dale, Rodney M; Kawakami, Koichi; Englert, Christoph; Chandra, Tamir; Schulte-Merker, Stefan

    2018-01-01

    Regenerative therapy for degenerative spine disorders requires the identification of cells that can slow down and possibly reverse degenerative processes. Here, we identify an unanticipated wound-specific notochord sheath cell subpopulation that expresses Wilms Tumor (WT) 1b following injury in zebrafish. We show that localized damage leads to Wt1b expression in sheath cells, and that wt1b+cells migrate into the wound to form a stopper-like structure, likely to maintain structural integrity. Wt1b+sheath cells are distinct in expressing cartilage and vacuolar genes, and in repressing a Wt1b-p53 transcriptional programme. At the wound, wt1b+and entpd5+ cells constitute separate, tightly-associated subpopulations. Surprisingly, wt1b expression at the site of injury is maintained even into adult stages in developing vertebrae, which form in an untypical manner via a cartilage intermediate. Given that notochord cells are retained in adult intervertebral discs, the identification of novel subpopulations may have important implications for regenerative spine disorder treatments. PMID:29405914

  17. Regulation of blood vessels by prolactin and vasoinhibins.

    Science.gov (United States)

    Clapp, Carmen; Thebault, Stéphanie; Macotela, Yazmín; Moreno-Carranza, Bibiana; Triebel, Jakob; Martínez de la Escalera, Gonzalo

    2015-01-01

    Prolactin (PRL) stimulates the growth of new blood vessels (angiogenesis) either directly through actions on endothelial cells or indirectly by upregulating proangiogenic factors like vascular endothelial growth factor (VEGF). Moreover, PRL acquires antiangiogenic properties after undergoing proteolytic cleavage to vasoinhibins, a family of PRL fragments (including 16 kDa PRL) with potent antiangiogenic, vasoconstrictive, and antivasopermeability effects. In view of the opposing actions of PRL and vasoinhibins, the regulation of the proteases responsible for specific PRL cleavage represents an efficient mechanism for controlling blood vessel growth and function. This review briefly describes the vascular actions of PRL and vasoinhibins, and addresses how their interplay could help drive biological effects of PRL in the context of health and disease.

  18. Stimulatory effect of clebopride on human prolactin secretion.

    Science.gov (United States)

    Perez-Lopez, F R; Legido, A; Sisskin, M; Abos, M D

    1980-11-01

    Serum levels of prolactin (PRL), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured in normally cycling women and normal men before and after oral admiministration of 1 mg of clebopride, a derivative of procainamide used in the treatment of gastrointestinal diseases. Clebopride produced a significant increase (P clebopride were noted upon the circulating levels of LH and FSH. The peak PRL response to clebopride was unaffected by pretreatment with 100 mg of nomifensine, although the secretory area from 120 to 210 minutes after clebopride was greater (P clebopride, the PRL response was completely abolished as compared with the control experiment (P clebopride could be the explanation for the occasional menstrual disorders and galactorrhea registered in some cases of long-term treatment.

  19. 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.

  20. 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

  1. From Bench to Bedside: Translating the Prolactin/Vasoinhibin Axis

    Directory of Open Access Journals (Sweden)

    Jakob Triebel

    2017-12-01

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

  2. Association of Neuropeptide Y (NPY), Interleukin-1B (IL1B) Genetic Variants and Correlation of IL1B Transcript Levels with Vitiligo Susceptibility

    Science.gov (United States)

    Laddha, Naresh C.; Dwivedi, Mitesh; Mansuri, Mohmmad Shoab; Singh, Mala; Patel, Hetanshi H.; Agarwal, Nishtha; Shah, Anish M.; Begum, Rasheedunnisa

    2014-01-01

    Background Vitiligo is a depigmenting disorder resulting from loss of functional melanocytes in the skin. NPY plays an important role in induction of immune response by acting on a variety of immune cells. NPY synthesis and release is governed by IL1B. Moreover, genetic variability in IL1B is reported to be associated with elevated NPY levels. Objectives Aim of the present study was to explore NPY promoter −399T/C (rs16147) and exon2 +1128T/C (rs16139) polymorphisms as well as IL1B promoter −511C/T (rs16944) polymorphism and to correlate IL1B transcript levels with vitiligo. Methods PCR-RFLP method was used to genotype NPY -399T/C SNP in 454 patients and 1226 controls; +1128T/C SNP in 575 patients and 1279 controls and IL1B −511C/T SNP in 448 patients and 785 controls from Gujarat. IL1B transcript levels in blood were also assessed in 105 controls and 95 patients using real-time PCR. Results Genotype and allele frequencies for NPY −399T/C, +1128T/C and IL1B −511C/T SNPs differed significantly (pvitiligo by 2.3 fold (pvitiligo (p = 0.015), also in female patients than male patients (p = 0.026). Genotype-phenotype correlation showed moderate association of IL1B -511C/T polymorphism with higher IL1B transcript levels. Trend analysis revealed significant difference between patients and controls for IL1B transcript levels with respect to different genotypes. Conclusion Our results suggest that NPY −399T/C, +1128T/C and IL1B −511C/T polymorphisms are associated with vitiligo and IL1B −511C/T SNP influences its transcript levels leading to increased risk for vitiligo in Gujarat population. Up-regulation of IL1B transcript in patients advocates its possible role in autoimmune pathogenesis of vitiligo. PMID:25221996

  3. Polycyclic phloroglucinols as PTP1B inhibitors from Hypericum longistylum: Structures, PTP1B inhibitory activities, and interactions with PTP1B.

    Science.gov (United States)

    Cao, Xiangrong; Yang, Xueyuan; Wang, Peixia; Liang, Yue; Liu, Feng; Tuerhong, Muhetaer; Jin, Da-Qing; Xu, Jing; Lee, Dongho; Ohizumi, Yasushi; Guo, Yuanqiang

    2017-12-01

    Protein tyrosine phosphatase 1B (PTP1B) has been regarded asa target for the research and development of new drugs to treat type II diabetes and PTP1B inhibitors are potential lead compounds for this type of new drugs. A phytochemical investigation to obtain new PTP1B inhibitors resulted in the isolation of four new phloroglucinols, longistyliones A-D (1-4) from the aerial parts of Hypericum longistylum. The structures of 1-4 were elucidated on the basis of extensive 1D and 2D NMR spectroscopic data analysis, and the absolute configurations of these compounds were established by comparing their experimental electronic circular dichroism (ECD) spectra with those calculated by the time-dependent density functional theory method. Compounds 1-4 possess a rare polycyclic phloroglucinol skeleton. The following biological evaluation revealed that all of the compounds showed PTP1B inhibitory effects. The further molecular docking studies indicated the strong interactions between these bioactive compounds with the PTP1B protein, which revealed the possible mechanism of PTP1B inhibition of bioactive compounds. All of the results implied that these compounds are potentially useful for the treatment of type II diabetes. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Increased dysbindin-1B isoform expression in schizophrenia and its propensity in aggresome formation

    Science.gov (United States)

    Xu, Yiliang; Sun, Yuhui; Ye, Haihong; Zhu, Li; Liu, Jianghong; Wu, Xiaofeng; Wang, Le; He, Tingting; Shen, Yan; Wu, Jane Y; Xu, Qi

    2015-01-01

    Genetic variations in the human dysbindin-1 gene (DTNBP1) have been associated with schizophrenia. As a result of alternative splicing, the human DTNBP1 gene generates at least three distinct protein isoforms, dysbindin-1A, -1B and -1C. Significant effort has focused on dysbindin-1A, an important player in multiple steps of neurodevelopment. However, the other isoforms, dysbindin-1B and dysbindin-1C have not been well characterized. Nor have been associated with human diseases. Here we report an increase in expression of DTNBP1b mRNA in patients with paranoid schizophrenia as compared with healthy controls. A single-nucleotide polymorphism located in intron 9, rs117610176, has been identified and associated with paranoid schizophrenia, and its C allele leads to an increase of DTNBP1b mRNA splicing. Our data show that different dysbindin splicing isoforms exhibit distinct subcellular distribution, suggesting their distinct functional activities. Dysbindin-1B forms aggresomes at the perinuclear region, whereas dysbindin-1A and -1C proteins exhibit diffused patterns in the cytoplasm. Dysbindin-1A interacts with dysbindin-1B, getting recruited to the aggresome structure when co-expressed with dysbindin-1B. Moreover, cortical neurons over-expressing dysbindin-1B show reduction in neurite outgrowth, suggesting that dysbindin-1B may interfere with dysbindin-1A function in a dominant-negative manner. Taken together, our study uncovers a previously unknown association of DTNBP1b expression with schizophrenia in addition to its distinct biochemical and functional properties. PMID:27462430

  5. 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. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Development Of Radioimmunoassay For Prolactin HORMONE Using Solid Phase Magnetic Particles

    International Nuclear Information System (INIS)

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

    2009-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1978-01-01

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

  8. high doses of prolactin inhibit testosterone secretion in rat leydig cells

    African Journals Online (AJOL)

    Femi Olaleye

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

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

    DEFF Research Database (Denmark)

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

    1998-01-01

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

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

    Science.gov (United States)

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

    2016-07-01

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

  11. Increased Prolactin Levels Are Associated with Impaired Processing Speed in Subjects with Early Psychosis

    OpenAIRE

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

    2014-01-01

    Hyperprolactinaemia, a common side effect of some antipsychotic drugs, is also present in drug-naïve psychotic patients and subjects at risk for psychosis. Recent studies in non-psychiatric populations suggest that increased prolactin may have negative effects on cognition. The aim of our study was to explore whether high plasma prolactin levels are associated with poorer cognitive functioning in subjects with early psychoses. We studied 107 participants: 29 healthy subjects and 78 subjects w...

  12. 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.

  13. Methylmercury inhibits prolactin release in a cell line of pituitary origin

    Directory of Open Access Journals (Sweden)

    L.A.L. Maués

    2015-08-01

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

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

    International Nuclear Information System (INIS)

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

    1981-01-01

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

  15. 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.

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

    Science.gov (United States)

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

    2004-04-01

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

  17. Social Context, Stress, Neuropsychiatric Disorders, and the Vasopressin 1b Receptor

    Directory of Open Access Journals (Sweden)

    Heather K. Caldwell

    2017-10-01

    Full Text Available The arginine vasopressin 1b receptor (Avpr1b is involved in the modulation of a variety of behaviors and is an important part of the mammalian hormonal stress axis. The Avpr1b is prominent in hippocampal CA2 pyramidal cells and in the anterior pituitary corticotrophs. Decades of research on this receptor has demonstrated its importance to the modulation of social recognition memory, social forms of aggression, and modulation of the hypothalamic-pituitary-adrenal axis, particularly under conditions of acute stress. Further, work in humans suggests that the Avpr1b may play a role in human neuropsychiatric disorders and its modulation may have therapeutic potential. This paper reviews what is known about the role of the Avpr1b in the context of social behaviors, the stress axis, and human neuropsychiatric disorders. Further, possible mechanisms for how Avpr1b activation within the hippocampus vs. Avpr1b activation within anterior pituitary may interact with one another to affect behavioral output are proposed.

  18. Dock/Nck facilitates PTP61F/PTP1B regulation of insulin signalling.

    Science.gov (United States)

    Wu, Chia-Lun; Buszard, Bree; Teng, Chun-Hung; Chen, Wei-Lin; Warr, Coral G; Tiganis, Tony; Meng, Tzu-Ching

    2011-10-01

    PTP1B (protein tyrosine phosphatase 1B) is a negative regulator of IR (insulin receptor) activation and glucose homoeostasis, but the precise molecular mechanisms governing PTP1B substrate selectivity and the regulation of insulin signalling remain unclear. In the present study we have taken advantage of Drosophila as a model organism to establish the role of the SH3 (Src homology 3)/SH2 adaptor protein Dock (Dreadlocks) and its mammalian counterpart Nck in IR regulation by PTPs. We demonstrate that the PTP1B orthologue PTP61F dephosphorylates the Drosophila IR in S2 cells in vitro and attenuates IR-induced eye overgrowth in vivo. Our studies indicate that Dock forms a stable complex with PTP61F and that Dock/PTP61F associate with the IR in response to insulin. We report that Dock is required for effective IR dephosphorylation and inactivation by PTP61F in vitro and in vivo. Furthermore, we demonstrate that Nck interacts with PTP1B and that the Nck/PTP1B complex inducibly associates with the IR for the attenuation of IR activation in mammalian cells. Our studies reveal for the first time that the adaptor protein Dock/Nck attenuates insulin signalling by recruiting PTP61F/PTP1B to its substrate, the IR.

  19. Aspirin Hydrolysis in Plasma Is a Variable Function of Butyrylcholinesterase and Platelet-activating Factor Acetylhydrolase 1b2 (PAFAH1b2)*

    Science.gov (United States)

    Zhou, Gang; Marathe, Gopal K.; Hartiala, Jaana; Hazen, Stanley L.; Allayee, Hooman; Tang, W. H. Wilson; McIntyre, Thomas M.

    2013-01-01

    Aspirin is rapidly hydrolyzed within erythrocytes by a heterodimer of PAFAH1b2/PAFAH1b3 but also in plasma by an unidentified activity. Hydrolysis in both compartments was variable, with a 12-fold variation in plasma among 2226 Cleveland Clinic GeneBank patients. Platelet inhibition by aspirin was suppressed in plasma that rapidly hydrolyzed aspirin. Plasma aspirin hydrolysis was significantly higher in patients with coronary artery disease compared with control subjects (16.5 ± 4.4 versus 15.1 ± 3.7 nmol/ml/min; p = 3.4 × 10−8). A genome-wide association study of 2054 GeneBank subjects identified a single locus immediately adjacent to the BCHE (butyrylcholinesterase) gene associated with plasma aspirin hydrolytic activity (lead SNP, rs6445035; p = 9.1 × 10−17). However, its penetrance was low, and plasma from an individual with an inactivating mutation in BCHE still effectively hydrolyzed aspirin. A second aspirin hydrolase was identified in plasma, the purification of which showed it to be homomeric PAFAH1b2. This is distinct from the erythrocyte PAFAH1b2/PAFAH1b3 heterodimer. Inhibitors showed that both butyrylcholinesterase (BChE) and PAFAH1b2 contribute to aspirin hydrolysis in plasma, with variation primarily reflecting non-genetic variation of BChE activity. Therefore, aspirin is hydrolyzed in plasma by two enzymes, BChE and a new extracellular form of platelet-activating factor acetylhydrolase, PAFAH1b2. Hydrolytic effectiveness varies widely primarily from non-genetic variation of BChE activity that affects aspirin bioavailability in blood and the ability of aspirin to inhibit platelet aggregation. PMID:23508960

  20. Aspirin hydrolysis in plasma is a variable function of butyrylcholinesterase and platelet-activating factor acetylhydrolase 1b2 (PAFAH1b2).

    Science.gov (United States)

    Zhou, Gang; Marathe, Gopal K; Hartiala, Jaana; Hazen, Stanley L; Allayee, Hooman; Tang, W H Wilson; McIntyre, Thomas M

    2013-04-26

    Aspirin is rapidly hydrolyzed within erythrocytes by a heterodimer of PAFAH1b2/PAFAH1b3 but also in plasma by an unidentified activity. Hydrolysis in both compartments was variable, with a 12-fold variation in plasma among 2226 Cleveland Clinic GeneBank patients. Platelet inhibition by aspirin was suppressed in plasma that rapidly hydrolyzed aspirin. Plasma aspirin hydrolysis was significantly higher in patients with coronary artery disease compared with control subjects (16.5 ± 4.4 versus 15.1 ± 3.7 nmol/ml/min; p = 3.4 × 10(-8)). A genome-wide association study of 2054 GeneBank subjects identified a single locus immediately adjacent to the BCHE (butyrylcholinesterase) gene associated with plasma aspirin hydrolytic activity (lead SNP, rs6445035; p = 9.1 × 10(-17)). However, its penetrance was low, and plasma from an individual with an inactivating mutation in BCHE still effectively hydrolyzed aspirin. A second aspirin hydrolase was identified in plasma, the purification of which showed it to be homomeric PAFAH1b2. This is distinct from the erythrocyte PAFAH1b2/PAFAH1b3 heterodimer. Inhibitors showed that both butyrylcholinesterase (BChE) and PAFAH1b2 contribute to aspirin hydrolysis in plasma, with variation primarily reflecting non-genetic variation of BChE activity. Therefore, aspirin is hydrolyzed in plasma by two enzymes, BChE and a new extracellular form of platelet-activating factor acetylhydrolase, PAFAH1b2. Hydrolytic effectiveness varies widely primarily from non-genetic variation of BChE activity that affects aspirin bioavailability in blood and the ability of aspirin to inhibit platelet aggregation.

  1. Protein tyrosine phosphatase 1B (PTP1B) is required for cardiac lineage differentiation of mouse embryonic stem cells.

    Science.gov (United States)

    Eshkiki, Zahra Shokati; Ghahremani, Mohammad Hossein; Shabani, Parisa; Firuzjaee, Sattar Gorgani; Sadeghi, Asie; Ghanbarian, Hossein; Meshkani, Reza

    2017-01-01

    Protein tyrosine phosphatase 1B (PTP1B) has been shown to regulate multiple cellular events such as differentiation, cell growth, and proliferation; however, the role of PTP1B in differentiation of embryonic stem (ES) cells into cardiomyocytes remains unexplored. In the present study, we investigated the effects of PTP1B inhibition on differentiation of ES cells into cardiomyocytes. PTP1B mRNA and protein levels were increased during the differentiation of ES cells into cardiomyocytes. Accordingly, a stable ES cell line expressing PTP1B shRNA was established. In vitro, the number and size of spontaneously beating embryoid bodies were significantly decreased in PTP1B-knockdown cells, compared with the control cells. Decreased expression of cardiac-specific markers Nkx2-5, MHC-α, cTnT, and CX43, as assessed by real-time PCR analysis, was further confirmed by immunocytochemistry of the markers. The results also showed that PTP1B inhibition induced apoptosis in both differentiated and undifferentiated ES cells, as presented by increasing the level of cleaved caspase-3, cytochrome C, and cleaved PARP. Further analyses revealed that PTP1B inhibition did not change proliferation and pluripotency of undifferentiated ES cells. Taken together, the data presented here suggest that PTP1B is essential for proper differentiation of ES cells into cardiomyocytes.

  2. PTP1B Inhibitors from the Entomogenous Fungi Isaria fumosorosea

    OpenAIRE

    Jun Zhang; Lin-Lin Meng; Jing-Jing Wei; Peng Fan; Sha-Sha Liu; Wei-Yu Yuan; You-Xing Zhao; Du-Qiang Luo

    2017-01-01

    Protein tyrosine phosphatase 1B (PTP1B) is implicated as a negative regulator of insulin receptor (IR) signaling and a potential drug target for the treatment of type II diabetes and other associated metabolic syndromes. Thus, small molecule inhibitors of PTP1B can be considered as an attractive approach for the design of new therapeutic agents of type II diabetes and cancer diseases. In a continuing search for new PTP1B inhibitors, a new tetramic acid possessing a rare pyrrolidinedione skele...

  3. Impact of IL1B gene polymorphisms and interleukin 1B levels on susceptibility to spontaneous preterm birth.

    Science.gov (United States)

    Langmia, Immaculate M; Apalasamy, Yamunah D; Omar, Siti Z; Mohamed, Zahurin

    2016-11-01

    Genetic factors influence susceptibility to preterm birth (PTB) and the immune pathway of PTB that involves the production of cytokines such as interleukins has been implicated in PTB disease. The aim of this study is to investigate the association of interleukin 1β (IL1B) gene polymorphisms and IL1B levels with spontaneous PTB. Peripheral maternal blood from 495 women was used for extraction of DNA and genotyping was carried out using the Sequenom MassARRAY platform. Maternal plasma was used to measure IL1B levels. There was no significant association between the allelic and genotype distribution of IL1B single nucleotide polymorphism (SNP) (rs1143634, rs1143627, rs16944) and the risk of PTB among Malaysian Malay women (rs1143634, P=0.722; rs1143627, P=0.543; rs16944, P=0.615). However, IL1B levels were significantly different between women who delivered preterm compared with those who delivered at term (P=0.030); high mean levels were observed among Malay women who delivered at preterm (mean=32.52) compared with term (mean=21.68). IL1B SNPs were not associated with IL1B plasma levels. This study indicates a significant association between IL1B levels and reduced risk of PTB among the Malaysian Malay women. This study shows the impact of IL1B levels on susceptibility to PTB disease; however, the high levels of IL1B observed among women in the preterm group are not associated with IL1B SNPs investigated in this study; IL1B high levels may be because of other factors not explored in this study and therefore warrant further investigation.

  4. Characterization of the oligosaccharide structure of human glycosylated prolactin (G-hPRL) native and recombinant

    International Nuclear Information System (INIS)

    Marcos Vinicius Nucci Capone

    2013-01-01

    Human prolactin (hPRL) is a polypeptide hormone secreted by the anterior pituitary under the regulation of the hypothalamus, involved in a variety of biological processes such as mammary gland development and lactation. The recombinant product is important in medical diagnosis and treatment of failure of lactation. This hormone may occur in the form of non-glycosylated protein (NGhPRL) and glycosylated (G-hPRL) with molecular weights of approximately 23 and 25 kilodalton (kDa), respectively; has a single N-glycosylation site located at asparagine (Asn) position 31, which is partially occupied, thus being a particularly interesting model of glycosylation. The biological activity of G-hPRL is lower compared to NG-hPRL (~4 times) and its physiological function is not well defined: the portion of carbohydrate appears to have an important role in the hormone biosynthesis, secretion, biological activity, and plasma survival of the hormone. The main objective of this study was to compare the structures of N-glycans present in glycosylated pituitary prolactin (G-hPRL-NHPP) with those present in the recombinant. To obtain the recombinant G-hPRL the production was performed in laboratory scale from Chinese hamster ovary cells (CHO), genetically modified and adapted to growth in suspension. Cycloheximide (CHX), whose main effect was to increase the ratio G-hPRL/NG-hPRL from 5% to 38% was added to the culture medium, thereby facilitating the purification of G-hPRL. The G-hPRL was purified in two steps, a cation exchanger followed by a purification by reversed-phase high performance liquid chromatography (RP-HPLC) which demonstrated the efficient separation of the two isoforms of hPRL. Recombinant G-hPRL-IPEN was well characterized by several techniques confirming its purity and biological activity, including comparisons with other reference preparation of pituitary origin purchased from the N ational Hormone & Peptide Program (NHPPU. S.) . The composition of N-glycans present

  5. Anxious moments for the protein tyrosine phosphatase PTP1B

    OpenAIRE

    Krishnan, Navasona; Tonks, Nicholas K.

    2015-01-01

    Chronic stress can lead to the development of anxiety and mood disorders. Thus, novel therapies for preventing adverse effects of stress are vitally important. Recently, the protein tyrosine phosphatase PTP1B was identified as a novel regulator of stress-induced anxiety. This opens up exciting opportunities to exploit PTP1B inhibitors as anxiolytics.

  6. 18 CFR 1b.9 - Confidentiality of investigations.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Confidentiality of investigations. 1b.9 Section 1b.9 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION... pursuant to subpoena, and all investigative proceedings shall be treated as nonpublic by the Commission and...

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

    Science.gov (United States)

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

    1994-02-01

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

  8. PTP1B Inhibitors from the Entomogenous Fungi Isaria fumosorosea

    Directory of Open Access Journals (Sweden)

    Jun Zhang

    2017-11-01

    Full Text Available Protein tyrosine phosphatase 1B (PTP1B is implicated as a negative regulator of insulin receptor (IR signaling and a potential drug target for the treatment of type II diabetes and other associated metabolic syndromes. Thus, small molecule inhibitors of PTP1B can be considered as an attractive approach for the design of new therapeutic agents of type II diabetes and cancer diseases. In a continuing search for new PTP1B inhibitors, a new tetramic acid possessing a rare pyrrolidinedione skeleton named fumosorinone A (1, together with five known ones 2–6 were isolated from the entomogenous fungus Isaria fumosorosea. The structures of 2–6 were elucidated by extensive spectroscopic analysis. Fumosorinone A (1 and beauvericin (6 showed significant PTP1B inhibitory activity with IC50 value of 3.24 μM and 0.59 μM.

  9. PTP1B targets the endosomal sorting machinery

    DEFF Research Database (Denmark)

    Stuible, Matthew; Abella, Jasmine V; Feldhammer, Matthew

    2010-01-01

    Dephosphorylation and endocytic down-regulation are distinct processes that together control the signaling output of a variety of receptor tyrosine kinases (RTKs). PTP1B can directly dephosphorylate several RTKs, but it can also promote activation of downstream pathways through largely unknown...... mechanisms. These positive signaling functions likely contribute to the tumor-promoting effect of PTP1B in mouse cancer models. Here, we have identified STAM2, an endosomal protein involved in sorting activated RTKs for lysosomal degradation, as a substrate of PTP1B. PTP1B interacts with STAM2 at defined...... phosphotyrosine sites, and knockdown of PTP1B expression augments STAM2 phosphorylation. Intriguingly, manipulating the expression and phosphorylation state of STAM2 did not have a general effect on epidermal growth factor (EGF)-induced EGF receptor trafficking, degradation, or signaling. Instead, phosphorylated...

  10. PTP1B Inhibitors from the Entomogenous Fungi Isaria fumosorosea.

    Science.gov (United States)

    Zhang, Jun; Meng, Lin-Lin; Wei, Jing-Jing; Fan, Peng; Liu, Sha-Sha; Yuan, Wei-Yu; Zhao, You-Xing; Luo, Du-Qiang

    2017-11-24

    Protein tyrosine phosphatase 1B (PTP1B) is implicated as a negative regulator of insulin receptor (IR) signaling and a potential drug target for the treatment of type II diabetes and other associated metabolic syndromes. Thus, small molecule inhibitors of PTP1B can be considered as an attractive approach for the design of new therapeutic agents of type II diabetes and cancer diseases. In a continuing search for new PTP1B inhibitors, a new tetramic acid possessing a rare pyrrolidinedione skeleton named fumosorinone A ( 1 ), together with five known ones 2 - 6 were isolated from the entomogenous fungus Isaria fumosorosea. The structures of 2 - 6 were elucidated by extensive spectroscopic analysis. Fumosorinone A ( 1 ) and beauvericin ( 6 ) showed significant PTP1B inhibitory activity with IC 50 value of 3.24 μM and 0.59 μM.

  11. 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.

  12. McCune-Albright syndrome: growth hormone and prolactin hypersecretion.

    Science.gov (United States)

    Christoforidis, Athanasios; Maniadaki, Ilianna; Stanhope, Richard

    2006-05-01

    McCune-Albright syndrome (MAS) has a special interest for endocrinologists as its pathogenesis results in hypersecretion of hormones in peripheral endocrine tissues. This can be expressed as precocious puberty, mainly in girls, primary hyperthyroidism, growth hormone (GH) and/or prolactin excess, hyperparathyroidism and hypercortisolism. The incidence of GH excess among patients with MAS has been assessed as up to 21%. The pathogenesis of GH hypersecretion in MAS is not completely understood, whereas it seems to be different from the aetiology of acromegaly/gigantism in non-MAS patients. The clinical expression of GH excess can be masked because of precocious puberty or craniofacial fibrous dysplasia, indicating the necessity for screening. Medical treatment is usually the only option in MAS patients with GH excess, as transsphenoidal surgery is usually restricted due to massive thickening of the skull base, whereas radiotherapy is contraindicated due to probable higher predisposition to sarcomatous transformation. The use of bromocriptine, cabergoline and octreotide, or the combination of these, has shown variable results, whereas pegvisomant, a GH receptor antagonist, is a new promising option, although not yet used in patients with MAS.

  13. Gender-related differences in prolactin secretion in pituitary prolactinomas

    International Nuclear Information System (INIS)

    Nishioka, H.; Haraoka, J.; Akada, K.; Azuma, S.

    2002-01-01

    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.)

  14. 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.

  15. Multiple metals predict prolactin and thyrotropin (TSH) levels in men

    International Nuclear Information System (INIS)

    Meeker, John D.; Rossano, Mary G.; Protas, Bridget; Diamond, Michael P.; Puscheck, Elizabeth; Daly, Douglas; Paneth, Nigel; Wirth, Julia J.

    2009-01-01

    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.

  16. Plasma homovanillic acid and prolactin in Huntington's disease.

    Science.gov (United States)

    Markianos, Manolis; Panas, Marios; Kalfakis, Nikos; Vassilopoulos, Dimitrios

    2009-05-01

    Dopaminergic activity is expected to be altered in patients with Huntington's disease (HD) and be related to factors like duration and severity of illness or patients' specific symptomatology like dementia, depression, or psychotic features. We assessed plasma homovanillic acid (pHVA) and plasma prolactin (pPRL), two correlates of dopaminergic activity, in 116 subjects with CAG repeats expansion in the HD gene, 26 presymptomatic (18 females) and 90 with overt symptomatology (43 females). Patients were evaluated using the Unified HD Rating Scale and the Total Functional Capacity Scale. Presence of dementia, depression, and psychotic features were also assessed. The age range of the patients was 22-83 years, duration of illness from 0.5 to 27 years, and CAG repeat number from 34 to 66. A group of 60 age and sex matched healthy subjects served as control group. Plasma PRL in subjects at risk and in neuroleptic-free patients, evaluated separately for males and females, did not differ from controls. Plasma HVA levels did not differ from controls in the group of presymptomatic subjects, but were significantly higher in the patients group. This increase was positively associated mainly with severity of illness and functional capacity of the patients, and not with presence of depression or dementia. Plasma HVA levels may be proven to be a peripheral index of disease progression. Reducing dopaminergic activity may have not only symptomatic, but also neuroprotective effects in HD.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2018-06-01

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

  19. 77 FR 3284 - Comment Request for Information Collection for the H-1B Technical Skills Training (H-1B) and the...

    Science.gov (United States)

    2012-01-23

    ... concerning the collection of data about H-1B Technical Skills Training (H-1B) [SGA/DFA PY-10-13] and H-1B... DEPARTMENT OF LABOR Comment Request for Information Collection for the H-1B Technical Skills Training (H-1B) and the H-1B Jobs and Innovation Accelerator Challenge (JIAC) Grant Programs, New...

  20. Role of CYP1B1 in PAH-DNA adduct formation and breast cancer risk

    Energy Technology Data Exchange (ETDEWEB)

    Goth-Goldstein, Regine; Russell, Marion L.; Muller, A.P.; Caleffi, M.; Eschiletti, J.; Graudenz, M.; Sohn, Michael D.

    2010-04-01

    This study investigated the hypothesis that increased exposure to polycyclic aromatic hydrocarbons (PAHs) increases breast cancer risk. PAHs are products of incomplete burning of organic matter and are present in cigarette smoke, ambient air, drinking water, and diet. PAHs require metabolic transformation to bind to DNA, causing DNA adducts, which can lead to mutations and are thought to be an important pre-cancer marker. In breast tissue, PAHs appear to be metabolized to their cancer-causing form primarily by the cytochrome P450 enzyme CYP1B1. Because the genotoxic impact of PAH depends on their metabolism, we hypothesized that high CYP1B1 enzyme levels result in increased formation of PAH-DNA adducts in breast tissue, leading to increased development of breast cancer. We have investigated molecular mechanisms of the relationship between PAH exposure, CYP1B1 expression and breast cancer risk in a clinic-based case-control study. We collected histologically normal breast tissue from 56 women (43 cases and 13 controls) undergoing breast surgery and analyzed these specimens for CYP1B1 genotype, PAH-DNA adducts and CYP1B1 gene expression. We did not detect any difference in aromatic DNA adduct levels of cases and controls, only between smokers and non-smokers. CYP1B1 transcript levels were slightly lower in controls than cases, but the difference was not statistically significant. We found no correlation between the levels of CYP1B1 expression and DNA adducts. If CYP1B1 has any role in breast cancer etiology it might be through its metabolism of estrogen rather than its metabolism of PAHs. However, due to the lack of statistical power these results should be interpreted with caution.

  1. Cyclin K and cyclin D1b are oncogenic in myeloma cells

    Directory of Open Access Journals (Sweden)

    Renoir Jack-Michel

    2010-05-01

    Full Text Available Abstract Background Aberrant expression of cyclin D1 is a common feature in multiple myeloma (MM and always associated with mantle cell lymphoma (MCL. CCND1 gene is alternatively spliced to produce two cyclin D1 mRNA isoforms which are translated in two proteins: cyclin D1a and cyclin D1b. Both isoforms are present in MM cell lines and primary cells but their relative role in the tumorigenic process is still elusive. Results To test the tumorigenic potential of cyclin D1b in vivo, we generated cell clones derived from the non-CCND1 expressing MM LP-1 cell line, synthesizing either cyclin D1b or cyclin K, a structural homolog and viral oncogenic form of cyclin D1a. Immunocompromised mice injected s.c. with LP-1K or LP-1D1b cells develop tumors at the site of injection. Genome-wide analysis of LP-1-derived cells indicated that several cellular processes were altered by cyclin D1b and/or cyclin K expression such as cell metabolism, signal transduction, regulation of transcription and translation. Importantly, cyclin K and cyclin D1b have no major action on cell cycle or apoptosis regulatory genes. Moreover, they impact differently cell functions. Cyclin K-expressing cells have lost their migration properties and display enhanced clonogenic capacities. Cyclin D1b promotes tumorigenesis through the stimulation of angiogenesis. Conclusions Our study indicates that cyclin D1b participates into MM pathogenesis via previously unrevealed actions.

  2. Tea Contains Potent Inhibitors of Tyrosine Phosphatase PTP1B

    OpenAIRE

    Ma, Junfeng; Li, Zhe; Xing, Shu; Ho, Wanting Tina; Fu, Xueqi; Zhao, Zhizhuang Joe

    2011-01-01

    Tea is widely consumed all over the world. Studies have demonstrated the role of tea in prevention and treatment of various chronic diseases including diabetes and obesity, but the underlying mechanism is unclear. PTP1B is a widely expressed tyrosine phosphatase which has been defined as a target for therapeutic drug development to treat diabetes and obesity. In screening for inhibitors of PTP1B, we found that aqueous extracts of teas exhibited potent PTP1B inhibitory effects with an IC50 val...

  3. [Solubilization Specificities Interferon beta-1b from Inclusion Bodies].

    Science.gov (United States)

    Zhuravko, A S; Kononova, N V; Bobruskin, A I

    2015-01-01

    A new solubilization method of recombinant interferon beta-1b (IFNβ-1b) from the inclusion bodies was developed. This method allows to extract the target protein selectively in the solutions of different alcohols, such as ethanol, propanol and isopropanol. It was shown that the more effective IFNβ-1b solubilization was achieved in the 55% propanol solution. This method allowed to extract the target protein from inclusion bodies around 85-90%, and significantly reduced Escherichia coli content in the solubilizate, in comparison with standard methods.

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

    International Nuclear Information System (INIS)

    Mai, Leemin; Pan, Jenntser

    1990-01-01

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

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

    Science.gov (United States)

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

    2007-02-15

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

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

    International Nuclear Information System (INIS)

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

    1986-01-01

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

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

    International Nuclear Information System (INIS)

    Ray, L.B.

    1985-01-01

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

  8. Impaired Integrin-mediated Adhesion and Signaling in Fibroblasts Expressing a Dominant-negative Mutant PTP1B

    Science.gov (United States)

    Arregui, Carlos O.; Balsamo, Janne; Lilien, Jack

    1998-01-01

    To investigate the role of nonreceptor protein tyrosine phosphatase 1B (PTP1B) in β1-integrin– mediated adhesion and signaling, we transfected mouse L cells with normal and catalytically inactive forms of the phosphatase. Parental cells and cells expressing the wild-type or mutant PTP1B were assayed for (a) adhesion, (b) spreading, (c) presence of focal adhesions and stress fibers, and (d) tyrosine phosphorylation. Parental cells and cells expressing wild-type PTP1B show similar morphology, are able to attach and spread on fibronectin, and form focal adhesions and stress fibers. In contrast, cells expressing the inactive PTP1B have a spindle-shaped morphology, reduced adhesion and spreading on fibronectin, and almost a complete absence of focal adhesions and stress fibers. Attachment to fibronectin induces tyrosine phosphorylation of focal adhesion kinase (FAK) and paxillin in parental cells and cells transfected with the wild-type PTP1B, while in cells transfected with the mutant PTP1B, such induction is not observed. Additionally, in cells expressing the mutant PTP1B, tyrosine phosphorylation of Src is enhanced and activity is reduced. Lysophosphatidic acid temporarily reverses the effects of the mutant PTP1B, suggesting the existence of a signaling pathway triggering focal adhesion assembly that bypasses the need for active PTP1B. PTP1B coimmunoprecipitates with β1-integrin from nonionic detergent extracts and colocalizes with vinculin and the ends of actin stress fibers in focal adhesions. Our data suggest that PTP1B is a critical regulatory component of integrin signaling pathways, which is essential for adhesion, spreading, and formation of focal adhesions. PMID:9813103

  9. Organic anion transporting polypeptide 1B transporters modulate hydroxyurea pharmacokinetics.

    Science.gov (United States)

    Walker, Aisha L; Lancaster, Cynthia S; Finkelstein, David; Ware, Russell E; Sparreboom, Alex

    2013-12-15

    Hydroxyurea is currently the only FDA-approved drug that ameliorates the pathophysiology of sickle cell anemia. Unfortunately, substantial interpatient variability in the pharmacokinetics (PK) of hydroxyurea may result in variation of the drug's efficacy. However, little is known about mechanisms that modulate hydroxyurea PK. Recent in vitro studies identifying hydroxyurea as a substrate for organic anion transporting polypeptide (OATP1B) transporters prompted the current investigation assessing the role of OATP1B transporters in modulating hydroxyurea PK. Using wild-type and Oatp1b knockout (Oatp1b(-/-)) mice, hydroxyurea PK was analyzed in vivo by measuring [(14)C]hydroxyurea distribution in plasma, kidney, liver, urine, or the exhaled (14)CO2 metabolite. Plasma levels were significantly reduced by 20% in Oatp1b(-/-) mice compared with wild-type (area under the curve of 38.64 or 48.45 μg·h(-1)·ml(-1), respectively) after oral administration, whereas no difference was observed between groups following intravenous administration. Accumulation in the kidney was significantly decreased by twofold in Oatp1b(-/-) mice (356.9 vs. 748.1 pmol/g), which correlated with a significant decrease in urinary excretion. Hydroxyurea accumulation in the liver was also decreased (136.6 vs. 107.3 pmol/g in wild-type or Oatp1b(-/-) mice, respectively) correlating with a decrease in exhaled (14)CO2. These findings illustrate that deficiency of Oatp1b transporters alters the absorption, distribution, and elimination of hydroxyurea thus providing the first in vivo evidence that cell membrane transporters may play a significant role in modulating hydroxyurea PK. Future studies to investigate other transporters and their role in hydroxyurea disposition are warranted for understanding the sources of variation in hydroxyurea's PK.

  10. PTP1B regulates Eph receptor function and trafficking

    OpenAIRE

    Nievergall, Eva; Janes, Peter W.; Stegmayer, Carolin; Vail, Mary E.; Haj, Fawaz G.; Teng, Shyh Wei; Neel, Benjamin G.; Bastiaens, Philippe I.; Lackmann, Martin

    2010-01-01

    Eph receptors orchestrate cell positioning during normal and oncogenic development. Their function is spatially and temporally controlled by protein tyrosine phosphatases (PTPs), but the underlying mechanisms are unclear and the identity of most regulatory PTPs are unknown. We demonstrate here that PTP1B governs signaling and biological activity of EphA3. Changes in PTP1B expression significantly affect duration and amplitude of EphA3 phosphorylation and biological function, whereas confocal ...

  11. Prolactin releasing effect of sulpiride isomers in rats and man

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, E E; Stefanini, E; Spano, P F [Cagliari Univ. (Italy). Inst. of Pharmacology and Pharmacognosy; Camanni, F; Massara, F [Turin Univ. (Italy). Chair of Endocrinology; Locatelli, V; Cocchi, D

    1979-01-01

    Sulpiride, an antipsychotropic drug of the benzamide class, reportedly displaces stereospecifically (/sup 3/H)-butyrophenones from putative dopamine (DA) binding sites in rat striatum. To evaluate if sulpiride displays the same stereospecifity in the inhibition of pituitary DA receptors, the effect of the two(-)-and (+)-sulpiride isomers was tested with regard to their ability to stimulate prolactin (PRL) secretion in rats and man and to displace (/sup 3/H)-spiroperidol bound to rat anterior pituitary receptors. In male rats, (-)-sulpiride at doses of 0.1 and 0.1 mg/kg i.p., induced a maximum PRL-releasing effect, not different from that evoked by a dose of 10 mg/kg of the compound. (+)-Sulpiride was active only at the dose of 10mg/kg i.p., and its PRL-releasing effect was superimposable to that evoked by the same dose of (-)-sulpiride. Similarily, in 8 normal subjects (4 men and 4 women) only (-)-sulpiride was active as PRL releaser when the low dose of 0.25 mg i.v. was used; when the higher dose of sulpiride was used (4.0 mg i.v.), it induced a rise in plasma PRL of the same entity for both isomers at early post-injection times (15-30 min) but greater with the (-)-isomer at the following time intervals (45-120 min). (-)-Sulpiride displaced (/sup 3/H)-spiroperidol bound to rat anterior pituitary homogenates with a potency about 100 times greater as that showed by (+)-sulpiride. In all, these data indicate that sulpiride isomers display at the level of pituitary DA receptors for PRL control the same stereospecifity exhibited on a population of striatal DA receptors.

  12. ARID1B alterations identify aggressive tumors in neuroblastoma.

    Science.gov (United States)

    Lee, Soo Hyun; Kim, Jung-Sun; Zheng, Siyuan; Huse, Jason T; Bae, Joon Seol; Lee, Ji Won; Yoo, Keon Hee; Koo, Hong Hoe; Kyung, Sungkyu; Park, Woong-Yang; Sung, Ki W

    2017-07-11

    Targeted panel sequencing was performed to determine molecular targets and biomarkers in 72 children with neuroblastoma. Frequent genetic alterations were detected in ALK (16.7%), BRCA1 (13.9%), ATM (12.5%), and PTCH1 (11.1%) in an 83-gene panel. Molecular targets for targeted therapy were identified in 16 of 72 patients (22.2%). Two-thirds of ALK mutations were known to increase sensitivity to ALK inhibitors. Sequence alterations in ARID1B were identified in 5 of 72 patients (6.9%). Four of five ARID1B alterations were detected in tumors of high-risk patients. Two of five patients with ARID1B alterations died of disease progression. Relapse-free survival was lower in patients with ARID1B alterations than in those without (p = 0.01). In analysis confined to high-risk patients, 3-year overall survival was lower in patients with an ARID1B alteration (33.3 ± 27.2%) or MYCN amplification (30.0 ± 23.9%) than in those with neither ARID1B alteration nor MYCN amplification (90.5 ± 6.4%, p = 0.05). These results provide possibilities for targeted therapy and a new biomarker identifying a subgroup of neuroblastoma patients with poor prognosis.

  13. Space Launch Systems Block 1B Preliminary Navigation System Design

    Science.gov (United States)

    Oliver, T. Emerson; Park, Thomas; Anzalone, Evan; Smith, Austin; Strickland, Dennis; Patrick, Sean

    2018-01-01

    NASA is currently building the Space Launch Systems (SLS) Block 1 launch vehicle for the Exploration Mission 1 (EM-1) test flight. In parallel, NASA is also designing the Block 1B launch vehicle. The Block 1B vehicle is an evolution of the Block 1 vehicle and extends the capability of the NASA launch vehicle. This evolution replaces the Interim Cryogenic Propulsive Stage (ICPS) with the Exploration Upper Stage (EUS). As the vehicle evolves to provide greater lift capability, increased robustness for manned missions, and the capability to execute more demanding missions so must the SLS Integrated Navigation System evolved to support those missions. This paper describes the preliminary navigation systems design for the SLS Block 1B vehicle. The evolution of the navigation hard-ware and algorithms from an inertial-only navigation system for Block 1 ascent flight to a tightly coupled GPS-aided inertial navigation system for Block 1B is described. The Block 1 GN&C system has been designed to meet a LEO insertion target with a specified accuracy. The Block 1B vehicle navigation system is de-signed to support the Block 1 LEO target accuracy as well as trans-lunar or trans-planetary injection accuracy. Additionally, the Block 1B vehicle is designed to support human exploration and thus is designed to minimize the probability of Loss of Crew (LOC) through high-quality inertial instruments and robust algorithm design, including Fault Detection, Isolation, and Recovery (FDIR) logic.

  14. Serum Prolactin Levels in Patients with Major Depressive Disorder Receiving Selective Serotonin-Reuptake Inhibitor Monotherapy for 3 Months: A Prospective Study

    OpenAIRE

    Park, Young-Min

    2017-01-01

    Objective It is unclear whether selective serotonin-reuptake inhibitors (SSRIs) can significantly increase the prolactin level. The purpose of this study was to identify the relationship between the prolactin level and the administration of SSRIs such as escitalopram and sertraline. An additional purpose was to determine whether the elevation of prolactin differs between escitalopram and sertraline treatment. Methods Serum prolactin levels were measured at baseline and after 3 months in 23 pa...

  15. Organic anion transporter 3- and organic anion transporting polypeptides 1B1- and 1B3-mediated transport of catalposide

    Directory of Open Access Journals (Sweden)

    Jeong HU

    2015-01-01

    Full Text Available Hyeon-Uk Jeong,1 Mihwa Kwon,2 Yongnam Lee,3 Ji Seok Yoo,3 Dae Hee Shin,3 Im-Sook Song,2 Hye Suk Lee1 1College of Pharmacy, The Catholic University of Korea, Bucheon 420-743, Korea; 2College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Korea; 3Central R&D Institute, Yungjin Pharm Co., Ltd., Suwon 443-270, Korea Abstract: We investigated the in vitro transport characteristics of catalposide in HEK293 cells overexpressing organic anion transporter 1 (OAT1, OAT3, organic anion transporting polypeptide 1B1 (OATP1B1, OATP1B3, organic cation transporter 1 (OCT1, OCT2, P-glycoprotein (P-gp, and breast cancer resistance protein (BCRP. The transport mechanism of catalposide was investigated in HEK293 and LLC-PK1 cells overexpressing the relevant transporters. The uptake of catalposide was 319-, 13.6-, and 9.3-fold greater in HEK293 cells overexpressing OAT3, OATP1B1, and OATP1B3 transporters, respectively, than in HEK293 control cells. The increased uptake of catalposide via the OAT3, OATP1B1, and OATP1B3 transporters was decreased to basal levels in the presence of representative inhibitors such as probenecid, furosemide, and cimetidine (for OAT3 and cyclosporin A, gemfibrozil, and rifampin (for OATP1B1 and OATP1B3. The concentration-dependent OAT3-mediated uptake of catalposide revealed the following kinetic parameters: Michaelis constant (Km =41.5 µM, maximum uptake rate (Vmax =46.2 pmol/minute, and intrinsic clearance (CLint =1.11 µL/minute. OATP1B1- and OATP1B3-mediated catalposide uptake also showed concentration dependency, with low CLint values of 0.035 and 0.034 µL/minute, respectively. However, the OCT1, OCT2, OAT1, P-gp, and BCRP transporters were apparently not involved in the uptake of catalposide into cells. In addition, catalposide inhibited the transport activities of OAT3, OATP1B1, and OATP1B3 with half-maximal inhibitory concentration values of 83, 200, and 235 µ

  16. 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.

  17. Studies on Purification and Coatation of Polyclonal Antibody for Prolactin Solid Phase Radioimmunoassay in Human Serum

    International Nuclear Information System (INIS)

    El-Bayoumy, A.S.A.; Sallam, Kh.M.; Shafik, H.M.

    2012-01-01

    The objective of the present study was oriented to produce purified polyclonal antibody to prepare a prolactin solid phase coated tubes radioimmunoassay system. In the present study, production of polyclonal antibodies was carried out through immunization of three healthy white male mature New Zealand rabbits with a highly purified sheep prolactin antigen. The obtained anti-sera was purified using an anion exchange reactive group, diethylamino ethyle (DEAE) covalently linked to Sepharose. The purified polyclonal antibody was used for coating polystyrene tubes. The preparation of 125 I-prolactin tracer was carried out using chloramine-T method. The preparation of standards was performed using assay buffer to cover the range from 2 to 200 ng/ml. The optimization and validation tests of the assay were performed to evaluate the validity of the prepared system. In conclusion, this low cost assay would be used in diagnosis of pituitary dysfunction and diagnosis of infertility in males and females

  18. Studies on Purification and Coatation of Polyclonal Antibody for Prolactin Solid Phase Radioimmunoassay in Human Serum

    International Nuclear Information System (INIS)

    El-Bayoumy, A.S.A.; Sallam, Kh.M.; Shafik, H.M.

    2014-01-01

    The objective of the present study was oriented to produce purified polyclonal antibody to prepare a prolactin solid phase coated tubes radioimmunoassay system. In the present study, production of polyclonal antibodies was carried out through immunization of three healthy white male mature New Zealand rabbits with a highly purified sheep prolactin antigen. The obtained anti-sera was purified using an anion exchange reactive group, diethylamino ethyle (DEAE) covalently linked to Sepharose. The purified polyclonal antibody was used for coating polystyrene tubes. The preparation of 125 I-prolactin tracer was carried out using chloramine-T method. The preparation of standards was performed using assay buffer to cover the range from 2 to 200 ng/ml. The optimization and validation tests of the assay were performed to evaluate the validity of the prepared system. In conclusion, this low cost assay would be used in diagnosis of pituitary dysfunction and diagnosis of infertility in males and females.

  19. Radioimmunoassay of human homologous prolactin in serum with commercially available reagents

    International Nuclear Information System (INIS)

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

    1977-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1990-01-01

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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

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

    International Nuclear Information System (INIS)

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

    1983-01-01

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

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

    Science.gov (United States)

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

    2017-03-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1976-11-01

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

  5. Exogenous and Endogeneous Disialosyl Ganglioside GD1b Induces Apoptosis of MCF-7 Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Sun-Hyung Ha

    2016-04-01

    Full Text Available Gangliosides have been known to play a role in the regulation of apoptosis in cancer cells. This study has employed disialyl-ganglioside GD1b to apoptosis in human breast cancer MCF-7 cells using exogenous treatment of the cells with GD1b and endogenous expression of GD1b in MCF-7 cells. First, apoptosis in MCF-7 cells was observed after treatment of GD1b. Treatment of MCF-7 cells with GD1b reduced cell growth rates in a dose and time dependent manner during GD1b treatment, as determined by XTT assay. Among the various gangliosides, GD1b specifically induced apoptosis of the MCF-7 cells. Flow cytometry and immunofluorescence assays showed that GD1b specifically induces apoptosis in the MCF-7 cells with Annexin V binding for apoptotic actions in early stage and propidium iodide (PI staining the nucleus of the MCF-7 cells. Treatment of MCF-7 cells with GD1b activated apoptotic molecules such as processed forms of caspase-8, -7 and PARP (Poly(ADP-ribose polymerase, without any change in the expression of mitochondria-mediated apoptosis molecules such as Bax and Bcl-2. Second, to investigate the effect of endogenously produced GD1b on the regulation of cell function, UDP-gal: β1,3-galactosyltransferase-2 (GD1b synthase, Gal-T2 gene has been transfected into the MCF-7 cells. Using the GD1b synthase-transfectants, apoptosis-related signal proteins linked to phenotype changes were examined. Similar to the exogenous GD1b treatment, the cell growth of the GD1b synthase gene-transfectants was significantly suppressed compared with the vector-transfectant cell lines and transfection activated the apoptotic molecules such as processed forms of caspase-8, -7 and PARP, but not the levels of expression of Bax and Bcl-2. GD1b-induced apoptosis was blocked by caspase inhibitor, Z-VAD. Therefore, taken together, it was concluded that GD1b could play an important role in the regulation of breast cancer apoptosis.

  6. PTP1B antisense oligonucleotide lowers PTP1B protein, normalizes blood glucose, and improves insulin sensitivity in diabetic mice

    Science.gov (United States)

    Zinker, Bradley A.; Rondinone, Cristina M.; Trevillyan, James M.; Gum, Rebecca J.; Clampit, Jill E.; Waring, Jeffrey F.; Xie, Nancy; Wilcox, Denise; Jacobson, Peer; Frost, Leigh; Kroeger, Paul E.; Reilly, Regina M.; Koterski, Sandra; Opgenorth, Terry J.; Ulrich, Roger G.; Crosby, Seth; Butler, Madeline; Murray, Susan F.; McKay, Robert A.; Bhanot, Sanjay; Monia, Brett P.; Jirousek, Michael R.

    2002-01-01

    The role of protein-tyrosine phosphatase 1B (PTP1B) in diabetes was investigated using an antisense oligonucleotide in ob/ob and db/db mice. PTP1B antisense oligonucleotide treatment normalized plasma glucose levels, postprandial glucose excursion, and HbA1C. Hyperinsulinemia was also reduced with improved insulin sensitivity. PTP1B protein and mRNA were reduced in liver and fat with no effect in skeletal muscle. Insulin signaling proteins, insulin receptor substrate 2 and phosphatidylinositol 3 (PI3)-kinase regulatory subunit p50α, were increased and PI3-kinase p85α expression was decreased in liver and fat. These changes in protein expression correlated with increased insulin-stimulated protein kinase B phosphorylation. The expression of liver gluconeogenic enzymes, phosphoenolpyruvate carboxykinase, and fructose-1,6-bisphosphatase was also down-regulated. These findings suggest that PTP1B modulates insulin signaling in liver and fat, and that therapeutic modalities targeting PTP1B inhibition may have clinical benefit in type 2 diabetes. PMID:12169659

  7. Covalent Allosteric Inactivation of Protein Tyrosine Phosphatase 1B (PTP1B) by an Inhibitor-Electrophile Conjugate.

    Science.gov (United States)

    Punthasee, Puminan; Laciak, Adrian R; Cummings, Andrea H; Ruddraraju, Kasi Viswanatharaju; Lewis, Sarah M; Hillebrand, Roman; Singh, Harkewal; Tanner, John J; Gates, Kent S

    2017-04-11

    Protein tyrosine phosphatase 1B (PTP1B) is a validated drug target, but it has proven difficult to develop medicinally useful, reversible inhibitors of this enzyme. Here we explored covalent strategies for the inactivation of PTP1B using a conjugate composed of an active site-directed 5-aryl-1,2,5-thiadiazolidin-3-one 1,1-dioxide inhibitor connected via a short linker to an electrophilic α-bromoacetamide moiety. Inhibitor-electrophile conjugate 5a caused time-dependent loss of PTP1B activity consistent with a covalent inactivation mechanism. The inactivation occurred with a second-order rate constant of (1.7 ± 0.3) × 10 2 M -1 min -1 . Mass spectrometric analysis of the inactivated enzyme indicated that the primary site of modification was C121, a residue distant from the active site. Previous work provided evidence that covalent modification of the allosteric residue C121 can cause inactivation of PTP1B [Hansen, S. K., Cancilla, M. T., Shiau, T. P., Kung, J., Chen, T., and Erlanson, D. A. (2005) Biochemistry 44, 7704-7712]. Overall, our results are consistent with an unusual enzyme inactivation process in which noncovalent binding of the inhibitor-electrophile conjugate to the active site of PTP1B protects the nucleophilic catalytic C215 residue from covalent modification, thus allowing inactivation of the enzyme via selective modification of allosteric residue C121.

  8. 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.

  9. Growth hormone and prolactin radioimmunoassay in early diagnosis of pituitary tumors

    International Nuclear Information System (INIS)

    Gembicki, M.; Kosowicz, J.

    1978-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Patel Osman V

    2009-03-01

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

  11. Characterization of the natural kaolinite KGa-1b

    International Nuclear Information System (INIS)

    Puukko, E.; Hakanen, M.

    2003-05-01

    Kaolinite is a common mineral on the surfaces of fractures in the rock. The sorption of europium and americium on kaolinite has been studied in a previous study (Puukko and Hakanen, 2001) using a natural kaolinite, KGa-1b (from the Clay Mineral Society, USA). Before experiments the kaolinite was washed with acid (HCl). The washing with acid removed iron but not TiO 2 . Surface complexation model has been applied to model the acid base reactions of kaolinite and the sorption of americium and europium on the kaolinite. In the present work the sorption of europium on the natural kaolinite KGa-1b was studied. The characterization of the natural kaolinite KGa- 1b is needed in the modelling of the sorption experiments. The iron impurities in the kaolinite were extracted with phase selective solutions to determine if the iron was amorphous and crystalline. The dissociation constants of kaolinite KGa-1b were determined by acid base titration in 0.05 M, 0.1 M and 0.5 M NaNO 3 solutions by two methods: a continuous titration and a batch titration. The solutions of the batch titrations were analysed for dissolved cations and silica and lanthanides at the laboratory of the Geological Survey of Finland (GSF). The loss in ignition of the KGa-1b was 14.3 w-% according to the Clay Mineral Society. The possible presence of humic acids was investigated at the GSF using thermogravimetry, X-ray diffraction and IR spectrometry and in the Laboratory of Physical Chemistry by measuring IR-absorption of gases released from a heated sample. The kaolinite KGa-1b contains a small quantity of iron. The phase selective extraction of amorphous iron gave almost same results as crystalline iron. The quantities of pure iron oxide phases of the total iron content was very low. The thermogravimetry and XRD analysis of the kaolinite KGa-1b indicated no presence of organic impurities, especially humic acids. The sensitivity of the IR analysis was not high enough to detect humic acids in the kaolinite

  12. Snail recruits Ring1B to mediate transcriptional repression and cell migration in pancreatic cancer cells.

    Science.gov (United States)

    Chen, Jiangzhi; Xu, Hong; Zou, Xiuqun; Wang, Jiamin; Zhu, Yi; Chen, Hao; Shen, Baiyong; Deng, Xiaxing; Zhou, Aiwu; Chin, Y Eugene; Rauscher, Frank J; Peng, Chenghong; Hou, Zhaoyuan

    2014-08-15

    Transcriptional repressor Snail is a master regulator of epithelial-mesenchymal transition (EMT), yet the epigenetic mechanism governing Snail to induce EMT is not well understood. Here, we report that in pancreatic ductal adenocarcinoma (PDAC), elevated levels of the ubiquitin E3 ligase Ring1B and Snail, along with elevated monoubiquitination of H2A at K119 (H2AK119Ub1), are highly correlated with poor survival. Mechanistic investigations identified Ring1B as a Snail-interacting protein and showed that the carboxyl zinc fingers of Snail recruit Ring1B and its paralog Ring1A to repress its target promoters. Simultaneous depletion of Ring1A and Ring1B in pancreatic cancer cells decreased Snail binding to the target chromatin, abolished H2AK119Ub1 modification, and thereby compromised Snail-mediated transcriptional repression and cell migration. We found that Ring1B and the SNAG-associated chromatin modifier EZH2 formed distinct protein complexes with Snail and that EZH2 was required for Snail-Ring1A/B recruitment to the target promoter. Collectively, our results unravel an epigenetic mechanism underlying transcriptional repression by Snail, suggest Ring1A/B as a candidate therapeutic target, and identify H2AK119Ub1 as a potential biomarker for PDAC diagnosis and prognosis. ©2014 American Association for Cancer Research.

  13. Voltage-Gated Sodium Channel β1/β1B Subunits Regulate Cardiac Physiology and Pathophysiology

    Directory of Open Access Journals (Sweden)

    Nnamdi Edokobi

    2018-04-01

    Full Text Available Cardiac myocyte contraction is initiated by a set of intricately orchestrated electrical impulses, collectively known as action potentials (APs. Voltage-gated sodium channels (NaVs are responsible for the upstroke and propagation of APs in excitable cells, including cardiomyocytes. NaVs consist of a single, pore-forming α subunit and two different β subunits. The β subunits are multifunctional cell adhesion molecules and channel modulators that have cell type and subcellular domain specific functional effects. Variants in SCN1B, the gene encoding the Nav-β1 and -β1B subunits, are linked to atrial and ventricular arrhythmias, e.g., Brugada syndrome, as well as to the early infantile epileptic encephalopathy Dravet syndrome, all of which put patients at risk for sudden death. Evidence over the past two decades has demonstrated that Nav-β1/β1B subunits play critical roles in cardiac myocyte physiology, in which they regulate tetrodotoxin-resistant and -sensitive sodium currents, potassium currents, and calcium handling, and that Nav-β1/β1B subunit dysfunction generates substrates for arrhythmias. This review will highlight the role of Nav-β1/β1B subunits in cardiac physiology and pathophysiology.

  14. 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.

  15. Effect of Interleukin 1b on rat thymus microenvironment

    Directory of Open Access Journals (Sweden)

    M Artico

    2009-12-01

    Full Text Available The effect of interleukin 1b on the thymus of control and chemically sympathectomized adult and aged rats was studied with the aim of assessing the importance of adrenergic nerve fibres (ANF in the regulation of some immunological functions.The whole thymus was removed from normal, sympathectomized (with the neurotoxin 6-OH-dopamine and treated (interleukin 1b rats. Thymic slices were stained with eosin orange (for the recognition of microanatomical details of the thymic microenvironment and with Bodian’s method for staining of nerve fibres. Histofluorescence microscopy was employed for staining ANF and immunofluorescence was used for detecting NPY-like immunoreactivity. All images were submitted to quantitative morphometrical analysis and statistical analysis of data. Moreover, the amount of proteins and noradrenaline was measured on thymic homogenates. The results indicate that in normal conditions the formation of the thymic nerve plexi in the rat is complex: the majority of ANF are destroyed after chemical sympathectomy with 6-OH-dopamine and do not change after treatment with interleukin 1b; on the contrary, treatment with interleukin 1b induces substantial changes in the fresh weight of the thymus, the thymic microenvironment, thymic nerve fibers, ANF, NPY-like positive nerve fibres, and on the total amount of proteins and noradrenaline in rat thymic tissue homogenates.Immunostimulation with interleukin 1b induces substantial changes in the whole thymus, in its microenvironment and in ANF and NPY-like nerve fibres. After chemical sympathectomy, no significant immune response was evoked by interleukin 1b, since the majority of ANF was destroyed by chemical sympathectomy.

  16. Use of radioimmunoassay to diagnose some forms of endocrine sterility

    International Nuclear Information System (INIS)

    Balabolkin, M.I.; Gerasimov, G.A.

    1984-01-01

    The possibility is considered of using a metoclopramide test combined with radioimmunoassay for determing prolactin in the blood to diagnose some forms of endocrine sterility Of 17 women examined 5 are practically healthy, sterility of 6 women is caused by tumor of hypophysis verified by X-rayograms, 6 women suffered from disorderded prolactin secretion and sterility without roentgenologic signs of disordered sella turcica. Metoclopramide has been injected intravenously in the 10 mm dose. A series of advantages is noted of the metoclopramide sample characteristic of high availability of the preparation and practically complete absence of side-effects

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

    Science.gov (United States)

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

    2017-10-01

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

  18. Protein tyrosine phosphatase 1B (PTP1B) is dispensable for IgE-mediated cutaneous reaction in vivo.

    Science.gov (United States)

    Yang, Ting; Xie, Zhongping; Li, Hua; Yue, Lei; Pang, Zheng; MacNeil, Adam J; Tremblay, Michel L; Tang, Jin-Tian; Lin, Tong-Jun

    2016-01-01

    Mast cells play a critical role in allergic reactions. The cross-linking of FcεRI-bound IgE with multivalent antigen initiates a cascade of signaling events leading to mast cell activation. It has been well-recognized that cross linking of FcεRI mediates tyrosine phosphorylation. However, the mechanism involved in tyrosine dephosphorylation in mast cells is less clear. Here we demonstrated that protein tyrosine phosphatase 1B (PTP1B)-deficient mast cells showed increased IgE-mediated phosphorylation of the signal transducer and activator of transcription 5 (STAT5) and enhanced production of CCL9 (MIP-1γ) and IL-6 in IgE-mediated mast cells activation in vitro. However, IgE-mediated calcium mobilization, β-hexaosaminidase release (degranulation), and phosphorylation of IκB and MAP kinases were not affected by PTP1B deficiency. Furthermore, PTP1B deficient mice showed normal IgE-dependent passive cutaneous anaphylaxis and late phase cutaneous reactions in vivo. Thus, PTP1B specifically regulates IgE-mediated STAT5 pathway, but is redundant in influencing mast cell function in vivo. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    1980-01-01

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

  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

    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...... 40 different receptor chains, and reveals that the extracellular domain is merely the tip of a molecular iceberg....

  1. Analysis of Prolactin Gene Exon 4 Diversity in Peking, White Mojosari, and Peking White Mojosari Crossbreed

    Directory of Open Access Journals (Sweden)

    M. Indriati

    2016-04-01

    Full Text Available Genetic marker linked to loci reproductive traits could be used to increase an effectiveness of improvement in animal breeding. Association between DNA polymorphism and a trait could be considered as candidate genetic marker for marker assisted selection (MAS programs. Prolactin (PRL is one of polypeptide hormones secreted by anterior pituitary gland in vertebrates. PRL plays an important role in onset of poultry incubation and brooding behavior. The aim of this study was to investigate the diversity of prolactin gene and to characterize the type of mutation in partial intron 3, intron 4 and exon 4 of duck prolactin gene. Blood extraction was collected from 168 ducks consisted of 19 Peking, 36 Mojosari, and 113 Peking White Mojosari (Peking Mojosari putih ducks. Polymerase chain reaction of fragment prolactin gene exon 4 and partial intron 3 and 4 have been successfully amplified with length of base pair were 496 bp. A total of 30 µL PCR product from each sample were sequenced for forward sequence using BIOTRACE 3730 by First Base Company, Malaysia. Alignment analysis found six SNP consisted of g.3941T>G, g.3975C>A, g.4110T>C, INDEL 3724A, INDEL 34031, and INDEL 3939A. Analysis of SNP frequency result indicated mutation of INDEL 3724A, g.3941T>G, g.3975C>A, INDEL 4031A and g.4110T>A in duck sample were polymorphic and INDEL 3939A were monomorphic.

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

    Science.gov (United States)

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

    2013-01-01

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

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

    International Nuclear Information System (INIS)

    El-Bayoumy, A.S.A.

    2012-01-01

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

  4. Serum prolactin, leptin, lipids and lipoproteins levels during antipsychotics treatment in Parkinson's disease and related psychosis.

    Science.gov (United States)

    Rustembegovic, Avdo; Sofic, Emin; Wichart, Ildiko

    2006-01-01

    Weight gain is a common adverse effect associated with the use of most typical and atypical antipsychotic. Aim of this study was to investigate serum prolactin, leptin, cholesterol, triglyceride, lipoproteins, such high density lipoprotein (HDL), and low density lipoprotein (LDL) levels in patients with Parkinson's disease (PD)-related psychosis during long-term medication with atypical antipsychotic. The study population comprised 40 patients, who were divided into 4 groups: olanzapine (n=10), risperidone (n=10), seroquel (n=10) monotherapy, a group of 10 patients receiving only antiparkinson drugs and a control group of 8 healthy persons. The patients were evaluated at baseline and at the sixth and twelfth week according to the Positive and Negative Syndrome Scale (PANSS), body mass index (BMI), and fasting serum prolactin, leptin, lipids and lipoproteins levels. Treatment of patients with olanzapine caused marked increase of serum LDL, cholesterol, triglyceride, and leptin levels (prelationship between serum leptin, lipid levels and BMI. However, treatment of patients with seroquel did not cause changes in serum prolactin, leptin, lipids, and lipoproteins levels. Our results suggest that treatment of patients with PD-related psychosis with seroquel appears to have minimal influence on serum leptin, prolactin, lipids, lipoproteins and BMI compared with olanzapine and risperidone.

  5. 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

    -hydroxyprogesterone and cortisol levels. In multiple regression analyses, prolactin was inversely associated with LDL and positively associated with estradiol, 17-hydroxyprogesterone and cortisol after correcting for age, BMI and smoking status in patients with PCOS. LIMITATIONS, REASONS FOR CAUTION: The study design...

  6. checkCIF/PLATON report Datablock: exp_1b

    Indian Academy of Sciences (India)

    THIS REPORT IS FOR GUIDANCE ONLY. IF USED AS PART OF A REVIEW PROCEDURE. FOR PUBLICATION, IT SHOULD NOT REPLACE THE EXPERTISE OF AN EXPERIENCED. CRYSTALLOGRAPHIC REFEREE. No syntax errors found. CIF dictionary Interpreting this report. Datablock: exp_1b. Bond precision:.

  7. 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

  8. New 5-deoxyflavonoids and their inhibitory effects on protein tyrosine phosphatase 1B (PTP1B) activity

    DEFF Research Database (Denmark)

    Nguyen, Phi Hung; Dao, Trong Tuan; Kim, Jayeon

    2011-01-01

    .9 ± 1.6 to 19.2 ± 1.1 μM), while compounds (3, 5, and 9) with 2,2-dimethylpyrano ring showed less inhibitory effect (IC₅₀ 22.6 ± 2.3 to 72.9 ± 9.7 μM). These results suggest that prenyl and methoxy groups may be responsible for the increase on the activity of 5-deoxyflavonoids against PTP1B......, but the presence of 2,2-dimethylpyrano ring on the B ring may be induced the decrease of PTP1B inhibitory activity....

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

    Science.gov (United States)

    Sharma, S. T.; Raff, H.

    2011-01-01

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

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

    International Nuclear Information System (INIS)

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

    1985-01-01

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

  11. Competitive protein tyrosine phosphatase 1B (PTP1B) inhibitors, prenylated caged xanthones from Garcinia hanburyi and their inhibitory mechanism.

    Science.gov (United States)

    Tan, Xue Fei; Uddin, Zia; Park, Chanin; Song, Yeong Hun; Son, Minky; Lee, Keun Woo; Park, Ki Hun

    2017-04-15

    Protein tyrosine phosphatase 1B (PTP1B) plays important role in diabetes, obesity and cancer. The methanol extract of the gum resin of Garcinia hanburyi (G. hanburyi) showed potent PTP1B inhibition at 10µg/ml. The active compounds were identified as prenylated caged xanthones (1-9) which inhibited PTP1B in dose-dependent manner. Carboxybutenyl group within caged motif (A ring) was found to play a critical role in enzyme inhibition such as 1-6 (IC 50 s=0.47-4.69µM), whereas compounds having hydroxymethylbutenyl 7 (IC 50 =70.25µM) and methylbutenyl 8 (IC 50 >200µM) showed less activity. The most potent inhibitor, gambogic acid 1 (IC 50 =0.47µM) showed 30-fold more potency than ursolic acid (IC 50 =15.5µM), a positive control. In kinetic study, all isolated xanthones behaved as competitive inhibitors which were fully demonstrated with K m , V max and K ik /K iv ratio. It was also proved that inhibitor 1 operated under the enzyme isomerization model having k 5 =0.0751µM - 1 S - 1 , k 6 =0.0249µM - 1 S - 1 and K i app =0.499µM. To develop a pharmacophore model, we explored the binding sites of compound 1 and 7 in PTP1B. These modeling results were in agreement with our findings, which revealed that the inhibitory activities are tightly related to caged motif and prenyl group in A ring. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Organic anion transporting polypeptide 1B transporters modulate hydroxyurea pharmacokinetics

    OpenAIRE

    Walker, Aisha L.; Lancaster, Cynthia S.; Finkelstein, David; Ware, Russell E.; Sparreboom, Alex

    2013-01-01

    Hydroxyurea is currently the only FDA-approved drug that ameliorates the pathophysiology of sickle cell anemia. Unfortunately, substantial interpatient variability in the pharmacokinetics (PK) of hydroxyurea may result in variation of the drug's efficacy. However, little is known about mechanisms that modulate hydroxyurea PK. Recent in vitro studies identifying hydroxyurea as a substrate for organic anion transporting polypeptide (OATP1B) transporters prompted the current investigation assess...

  13. Lithostratigraphy from downhole logs in Hole AND-1B, Antarctica

    Science.gov (United States)

    Williams, Trevor; Morin, Roger H.; Jarrard, Richard D.; Jackolski, Chris L.; Henrys, Stuart A.; Niessen, Frank; Magens, Diana; Kuhn, Gerhard; Monien, Donata; Powell, Ross D.

    2012-01-01

    The ANDRILL (Antarctic Drilling Project) McMurdo Ice Shelf (MIS) project drilled 1285 m of sediment in Hole AND–1B, representing the past 12 m.y. of glacial history. Downhole geophysical logs were acquired to a depth of 1018 mbsf (meters below seafloor), and are complementary to data acquired from the core. The natural gamma radiation (NGR) and magnetic susceptibility logs are particularly useful for understanding lithological and paleoenvironmental change at ANDRILL McMurdo Ice Shelf Hole AND–1B. NGR logs cover the entire interval from the seafloor to 1018 mbsf, and magnetic susceptibility and other logs covered the open hole intervals between 692 and 1018 and 237–342 mbsf. In the upper part of AND–1B, clear alternations between low and high NGR values distinguish between diatomite (lacking minerals containing naturally radioactive K, U, and Th) and diamictite (containing K-bearing clays, K-feldspar, mica, and heavy minerals). In the lower open hole logged section, NGR and magnetic susceptibility can also distinguish claystones (rich in K-bearing clay minerals, relatively low in magnetite) and diamictites (relatively high in magnetite). Sandstones can be distinguished by their high resistivity values in AND–1B. On the basis of these three downhole logs, diamictite, claystones, and sandstones can be predicted correctly for 74% of the 692–1018 mbsf interval. The logs were then used to predict facies for the 6% of this interval that was unrecovered by coring. Given the understanding of the physical property characteristics of different facies, it is also possible to identify subtle changes in lithology from the physical properties and help refine parts of the lithostratigraphy, for example, the varying terrigenous content of diatomites and the transitions from subice diamictite to open-water diatomite.

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

    Science.gov (United States)

    Brody, Stuart; Krüger, Tillmann H C

    2006-03-01

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

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

    Science.gov (United States)

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

    2014-01-29

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

  16. Urea, Uric Acid, Prolactin and fT4 Concentrations in Aqueous Humor of Keratoconus Patients.

    Science.gov (United States)

    Stachon, Tanja; Stachon, Axel; Hartmann, Ulrike; Seitz, Berthold; Langenbucher, Achim; Szentmáry, Nóra

    2017-06-01

    Keratoconus is a noninflammatory disease of the cornea associated with progressive thinning and conical shape. Metabolic alterations in the urea cycle, with changes in collagen fibril stability, oxidative stress, thyroid hormones and prolactin with regulatory effect on biosynthesis and biomechanical stability of corneal stroma, may all play a role in keratoconus etiology. Our purpose was to determine urea, uric acid, prolactin and free thyroxin (fT4) concentrations in human aqueous humor (hAH) of keratoconus and cataract patients. hAH was collected from 100 keratoconus (penetrating keratoplasty) (41.9 ± 14.9 years, 69 males) and 100 cataract patients (cataract surgery) (71.2 ± 12.4 years, 58 males). Urea, uric acid, prolactin and fT4 concentrations were measured by Siemens clinical chemistry or immunoassay system. For statistical analysis, a generalized linear model (GLM) was used. Urea concentration was 11.88 ± 3.03 mg/dl in keratoconus and 16.44 ± 6.40 mg/dl in cataract patients, uric acid 2.04 ± 0.59 mg/dl in keratoconus and 2.18 ± 0.73 mg/dl in cataract groups. Prolactin concentration was 3.18 ± 0.34 ng/ml in keratoconus and 3.33 ± 0.32 ng/ml in cataract patients, fT4 20.57 ± 4.76 pmol/l in KC and 19.06 ± 3.86 pmol/l in cataract group. Urea concentration was effected through gender (p = 0.039), age (p = 0.001) and diagnosis (p = 0.025). Uric acid concentration was not effected through any of the analyzed parameters (p > 0.056). Prolactin and fT4 concentration were effected only through diagnosis (p = 0.009 and p = 0.006). Urea and prolactin concentrations are decreased, fT4 concentration is increased in aqueous humor of keratoconus patients, and uric acid concentration remains unchanged. Urea concentration in aqueous humor is also increased in older and male patients. Therefore, metabolic disorder and hormonal balance may both have an impact on keratoconus development. Further studies are necessary to assess the specific impact.

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

    Science.gov (United States)

    Song, G G; Lee, Y H

    2017-10-01

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

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

    Science.gov (United States)

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

    1996-05-01

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

  19. Production of anti-IgG antibodies in sheep for using in the radioimmunoassays of LH, FSH and prolactin

    International Nuclear Information System (INIS)

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

    1996-01-01

    In this work described the production of second antibodies in sheep against rabbit IgG for being used in radioimmunoassays for determination LH, FSH and Prolactin. There was made the comparison between the results obtained using the Kits-RIA produced by us and the commercial WHO Kits-RIA, using these antibodies. The results allowed us to use these antibodies for production Kits-RIA of LH, FSH and Prolactin

  20. Microcystin-LR induces anoikis resistance to the hepatocyte uptake transporter OATP1B3-expressing cell lines

    International Nuclear Information System (INIS)

    Takano, Hiroyuki; Takumi, Shota; Ikema, Satoshi; Mizoue, Nozomi; Hotta, Yuki; Shiozaki, Kazuhiro; Sugiyama, Yasumasa; Furukawa, Tatsuhiko; Komatsu, Masaharu

    2014-01-01

    Microcystin-LR is a cyclic peptide released by several bloom-forming cyanobacteria. Understanding the mechanism of microcystin-LR toxicity is important, because of the both potencies of its acute cytotoxicity and tumor-promoting activity in hepatocytes of animals and humans. Recently, we have reported that the expression of human hepatocyte uptake transporter OATP1B3 was critical for the selective uptake of microcystin-LR into hepatocytes and for induction of its fatal cytotoxicity. In this study, we demonstrated a novel function of microcystin-LR which induced bipotential changes including anoikis resistance and cytoskeleton reorganization to OATP1B3-transfected HEK293 cells (HEK293-OATP1B3). After exposure to microcystin-LR, HEK293-OATP1B3 cells were divided to the floating cells and remaining adherent cells. After collection and reseeding the floating cells into a fresh flask, cells were confluently proliferated (HEK293-OATP1B3-FL) under the microcystin-LR-free condition. Both the proliferated HEK293-OATP1B3-FL and remaining adherent HEK293-OATP1B3-AD cells changed the character with down- and up-regulation of E-cadherin, respectively. Additionally, these cells acquired resistance to microcystin-LR. These results suggest that microcystin-LR could be associated with not only tumor promotion, but also epithelial–mesenchymal transition-mediated cancer metastasis. Furthermore, microcystin-LR might induce the cytoskeleton reorganization be accompanied epithelial–mesenchymal transition

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

    Directory of Open Access Journals (Sweden)

    Chakrapani Balijepalli

    2018-01-01

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

  2. Treatment of prolactin-secreting pituitary tumours in young women by needle implantation of radioactive yttrium

    International Nuclear Information System (INIS)

    Kelly, W.F.; Mashiter, K.; Doyle, F.H.; Banks, L.M.; Joplin, G.F.

    1978-01-01

    Twenty one young female patients with amenorrhoea, galactorrhoea or infertility were treated by 90 Y pituitary implantation of 20,000 rads. There was no morbidity. In all patients serum prolactin values were elevated and radiographs of the pituitary fossa were abnormal. After implantation the median fall in prolactin values was 60 per cent while there was no deterioration in pituitary function if normal pre-operatively. Luteinizing hormone values, both basally and following godanotrophin-releasing hormone, rose to normal after operation; several instances of sellar remodelling were observed radiologically, and no instance of relapse was found. So far nine patients desiring fertility have become pregnant, three without any additional therapy. No case of tumour expansion was observed during pregnancy. 90 Y implantation in patients requiring fertility is competitive with surgical methods, and together with a short course of bromocriptine if needed, could prove to be the treatment of choice. (author)

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    BACKGROUND: A blunted growth hormone and prolactin response to pharmacological stress test have previously been found in depressed patients, as well as an increased cortisol response to psychosocial stress. This study investigated these hormones in response to acute exercise using an incremental...... bicycle test. METHOD: A cross-sectional comparison of cortisol, growth hormone, and prolactin in depressed (n=137) and healthy (n=44) subjects during rest and in response to an incremental bicycle test. Secondly, we tested the depressed patients again after a 4-month randomized naturalistic exercise...... controls. The effect of acute exercise stress on PRL (p=.56) did not differ between depressed and healthy subjects. Apart from a decrease in GH response in the strength-training group (p=.03) the pragmatic exercise intervention did not affect resting hormonal levels, or the response to acute exercise...

  4. Osmoregulatory effects of hypophysectomy and homologous prolactin replacement in hybrid striped bass

    DEFF Research Database (Denmark)

    Jackson, Leslie F; McCormick, Stephen D; Madsen, Steffen S

    2005-01-01

    The effects of ovine prolactin (oPRL) and striped bass prolactin (sbPRL; Morone saxatilis) on plasma osmolality, electrolyte balance, and gill Na+,K+-ATPase activity were investigated in hypophysectomized (Hx), freshwater (FW)-acclimated, hybrid striped bass (M. saxatilis x Morone chrysops...... or 100 ng/g), or hormone vehicle (0.9% NaCl) at 48-h intervals (days 0, 2, 4, and 6) in FW and then sampled for blood plasma 24 h after the fourth injection (day 7). In Hx fish, oPRL (5 and 20 microg/g) and sbPRL (10 and 100 ng/g) were effective in maintaining plasma osmolality and levels of Na+, Cl...... balance in FW-adapted hybrid striped bass, and that this may involve downregulation of branchial Na+,K+-ATPase activity....

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

    Science.gov (United States)

    Onaka, Tatsushi; Takayanagi, Yuki; Leng, Gareth

    2010-05-01

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

  6. The effect of different radiation exposure combined with prolactin on the carcinogenesis of rat mammary tumors

    International Nuclear Information System (INIS)

    Yokoro Kenjiro

    1984-01-01

    Female W/Fu rats were exposed to various doses of respective radiation and some of these irradiated rats further received a continuous supply of prolactin by means of grafting a prolactin producing pituitary tumor as a promoter to make easier the detection of carcinogenic effect of radiation. The results show that, the carcinogenic effect of 2.0 MeV fission neutrons is surprisingly higher than those of others; being about 30, 14 and 4.5 times as high as X-rays, 14.1 MeV fast neutrons and 0.025 eV thermal neutrons respectively. The irradiation field of fission radiation is equivalent to the atomic bomb that exploded in Hiroshima in 1945, so these experimental findings may have some relevance to the recent study on the reassessment of radiation dose of both neutrons and gamma-rays produced by atomic bomb in Hiroshima and Nagasaki

  7. Prolactin-secreting pituitary adenoma in a man with gigantism: a case report.

    Science.gov (United States)

    Peillon, F; Philippon, J; Brandi, A M; Fohanno, D; Laplane, D; Dubois, M P; Decourt, J

    1979-12-01

    A prolactin-secreting pituitary adenoma was removed trans-sphenoidally from a 37 years old man with gigantism (218 cm). Serum levels of prolactin (PRL) were elevated pre-operatively and decreased after administration of L-Dopa with no increase after TRH as is usually observed in PRL-secreting adenomas. Growth hormone (GH) and somatomedin serum levels were normal with no modification of GH after insulin hypoglycemia, oral glucose loading or L-Dopa. Morphological examination of the tumour demonstrated the presence of lactotrophs by light and electron microscopy and by immunofluorescense staining. No somatotrophs were found. In this unique case, the relationship between a PRL-secreting adenoma and gigantism is discussed.

  8. Effect of Sulpirid on blood serum prolactin- and TSH-levels

    International Nuclear Information System (INIS)

    Foldes, J.; Gyertyanfi, G.; Borvendeg, J.

    1979-01-01

    Euthyreoid and hyperthyreoid women were subjected to examinations investigating the effect of a dopamine-antagonist (Sulpirid) on serum TSH and prolactin (LTH)-levels. For measurements of serum concentrations the following kits were used: prolactine: CIS; TSH: Ria-mat-TSH (Byk-Mallinkrodt); thyroxine: Tiopac T 4 (Amersham); triiodothyronine: Ria-mat-T 3 (Byk-Mallinkrodt). Sulpirid increased both the LTH and the TSH-levels. In case of hyperthyreosis the effect of Sulpirid on LTH-levels was less pronounced and it had no effect on serum-TSH at all. Pre-treatment with a dopamine-agonist (Bromocryptin) impeded the effect of Sulpirid. It is concluded that dopamine-receptors do have a role in the regulation of TSH-secretion in the hypophysis. (L.E.)

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

    Directory of Open Access Journals (Sweden)

    Sonia A Ronchetti

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

  10. Analysis of Prolactin Gene Exon 4 Diversity in Peking, White Mojosari, and Peking White Mojosari Crossbreed

    OpenAIRE

    M. Indriati; C. Sumantri; T. Susanti

    2016-01-01

    Genetic marker linked to loci reproductive traits could be used to increase an effectiveness of improvement in animal breeding. Association between DNA polymorphism and a trait could be considered as candidate genetic marker for marker assisted selection (MAS) programs. Prolactin (PRL) is one of polypeptide hormones secreted by anterior pituitary gland in vertebrates. PRL plays an important role in onset of poultry incubation and brooding behavior. The aim of this study was to investigate the...

  11. Pathology galactorrhea. Dynamic tests of prolactin secretion evaluation and the adenohypophyseal functional reserve

    International Nuclear Information System (INIS)

    Oliveira, B.C. de.

    1979-01-01

    Stimulus and supression tests of prolactin secretion and reserve evaluation of others hypophyseal trophin in thirty-seven patients, of feminine sex with galactorrhea and twelve normal volunteers with the objective of determinate the validity for etiologic diagnostic of pathologic galactorrhea are described. Simple radiography of brain and sella turcica on anteroposterior incidence and profile followed by plane tomography in all patients with pathological galactorrhea are also presented. (author)

  12. Lipidized prolactin-releasing peptide analogs: A new tool for obesity treatment

    Czech Academy of Sciences Publication Activity Database

    Maletínská, Lenka; Pražienková, Veronika; Zemenová, Jana; Popelová, Andrea; Blechová, Miroslava; Mikulášková, Barbora; Holubová, Martina; Železná, Blanka; Kuneš, Jaroslav

    2016-01-01

    Roč. 22, Suppl S2 (2016), S179-S180 ISSN 1075-2617. [European Peptide Symposium /34./ and International Peptide Symposium /8./. 04.09.2016-09.09.2016, Leipzig] R&D Projects: GA TA ČR(CZ) TE01020028; GA ČR(CZ) GA15-08679S Institutional support: RVO:61388963 Keywords : prolactin-releasing peptide * food intake * obesity Subject RIV: CE - Biochemistry

  13. Radioimmunoassay of haloperidol in human serum: correlation of serum haloperidol with serum prolactin

    International Nuclear Information System (INIS)

    Poland, R.E.; Rubin, R.T.

    1981-01-01

    A radioimmunoassay (RIA) for measurement of serum haloperidol is described. Compared to gaschromatography (GC), RIA vaues average 40% higher. However, a simple organic extraction of serum yields statistically equivalent RIA and GC haloperidol determinations. For both men and women combined, there was a positive correlation between dose (mg/kg/day) and steady-state serum haloperidol level (r = +0.86) and between steady-state serum haloperidol and serum prolactin (PRL) concentration

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

    International Nuclear Information System (INIS)

    Hassan, Ammar Mohamed Elamin

    2001-11-01

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

  15. Immunoradiometric assay for prolactin in serum and tissue; Comparison with radioimmunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Ohnami, Shumpei; Nakata, Hajime; Eto, Sumiya (University of Occupational and Environmental Health Hospital, Kitakyushu, Fukuoka (Japan))

    1990-09-01

    Prolactin (PRL) concentrations in sera and tumors of patients with various pituitary tumors were measured by both immunoradiometric assay (IRMA) and radioimmunoassay (RIA). PRL concentrations in sera and tumor tissues measured by IRMA were well correlated with those measured by RIA. PRL concentrations in sera reflected those of tumors removed. This IRMA is a simple and useful method for PRL determination in serum and tissue. (author).

  16. Plutonium disposition study phase 1b final report

    International Nuclear Information System (INIS)

    1993-01-01

    This report provides the results of the Westinghouse activities performed as part of the Plutonium Disposition Study Phase 1b. These activities, which took place from May 16, 1993 to September 15, 1993, build upon the work completed in Phase 1a, which concluded on May 15, 1993. In Phase 1a, three Plutonium Disposal Reactor (PDR) options were developed for the disposal of excess weapons grade plutonium from returned and dismantled nuclear weapons. This report documents the results of several tasks that were performed to further knowledge in specific areas leading up to Phase 2 of the PDR Study. The Westinghouse activities for Phase 1b are summarized as follows: (1) resolved technical issues concerning reactor physics including equilibrium cycle calculations, use of gadolinium, moderator temperature coefficient, and others as documented in Section 2.0; (2) analyzed large Westinghouse commercial plants for plutonium disposal; (3) reactor safety issues including the steam line break were resolved, and are included in Section 2.0; (4) several tasks related to the PDR Fuel Cycle were examined; (5) cost and deployment options were examined to determine optimal configuration for both plutonium disposal and tritium production; (6) response to questions from DOE and National Academy of Scientists (NAS) reviewers concerning the PDR Phase 1a report are included in Appendix A

  17. Molecular dynamics simulation study of PTP1B with allosteric inhibitor and its application in receptor based pharmacophore modeling

    Science.gov (United States)

    Bharatham, Kavitha; Bharatham, Nagakumar; Kwon, Yong Jung; Lee, Keun Woo

    2008-12-01

    Allosteric inhibition of protein tyrosine phosphatase 1B (PTP1B), has paved a new path to design specific inhibitors for PTP1B, which is an important drug target for the treatment of type II diabetes and obesity. The PTP1B1-282-allosteric inhibitor complex crystal structure lacks α7 (287-298) and moreover there is no available 3D structure of PTP1B1-298 in open form. As the interaction between α7 and α6-α3 helices plays a crucial role in allosteric inhibition, α7 was modeled to the PTP1B1-282 in open form complexed with an allosteric inhibitor (compound-2) and a 5 ns MD simulation was performed to investigate the relative orientation of the α7-α6-α3 helices. The simulation conformational space was statistically sampled by clustering analyses. This approach was helpful to reveal certain clues on PTP1B allosteric inhibition. The simulation was also utilized in the generation of receptor based pharmacophore models to include the conformational flexibility of the protein-inhibitor complex. Three cluster representative structures of the highly populated clusters were selected for pharmacophore model generation. The three pharmacophore models were subsequently utilized for screening databases to retrieve molecules containing the features that complement the allosteric site. The retrieved hits were filtered based on certain drug-like properties and molecular docking simulations were performed in two different conformations of protein. Thus, performing MD simulation with α7 to investigate the changes at the allosteric site, then developing receptor based pharmacophore models and finally docking the retrieved hits into two distinct conformations will be a reliable methodology in identifying PTP1B allosteric inhibitors.

  18. Purification and characterization of akr1b10 from human liver: role in carbonyl reduction of xenobiotics.

    Science.gov (United States)

    Martin, Hans-Jörg; Breyer-Pfaff, Ursula; Wsol, Vladimir; Venz, Simone; Block, Simone; Maser, Edmund

    2006-03-01

    Members of the aldo-keto reductase (AKR) superfamily have a broad substrate specificity in catalyzing the reduction of carbonyl group-containing xenobiotics. In the present investigation, a member of the aldose reductase subfamily, AKR1B10, was purified from human liver cytosol. This is the first time AKR1B10 has been purified in its native form. AKR1B10 showed a molecular mass of 35 kDa upon gel filtration and SDS-polyacrylamide gel electrophoresis. Kinetic parameters for the NADPH-dependent reduction of the antiemetic 5-HT3 receptor antagonist dolasetron, the antitumor drugs daunorubicin and oracin, and the carcinogen 4-methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK) to the corresponding alcohols have been determined by HPLC. Km values ranged between 0.06 mM for dolasetron and 1.1 mM for daunorubicin. Enzymatic efficiencies calculated as kcat/Km were more than 100 mM-1 min-1 for dolasetron and 1.3, 0.43, and 0.47 mM-1 min-1 for daunorubicin, oracin, and NNK, respectively. Thus, AKR1B10 is one of the most significant reductases in the activation of dolasetron. In addition to its reducing activity, AKR1B10 catalyzed the NADP+-dependent oxidation of the secondary alcohol (S)-1-indanol to 1-indanone with high enzymatic efficiency (kcat/Km=112 mM-1 min-1). The gene encoding AKR1B10 was cloned from a human liver cDNA library and the recombinant enzyme was purified. Kinetic studies revealed lower activity of the recombinant compared with the native form. Immunoblot studies indicated large interindividual variations in the expression of AKR1B10 in human liver. Since carbonyl reduction of xenobiotics often leads to their inactivation, AKR1B10 may play a role in the occurrence of chemoresistance of tumors toward carbonyl group-bearing cytostatic drugs.

  19. Prolactin receptors in liver, kidney, and gill of the tilapia (Oreochromis mossambicus): Characterization and effect of salinity on specific binding of iodinated ovine prolactin

    International Nuclear Information System (INIS)

    Dauder, S.; Young, G.; Hass, L.; Bern, H.A.

    1990-01-01

    Specific binding of 125 I-ovine prolactin (oPRL) to microsomal fractions from gill, kidney, and liver of adult tilapia was determined. Specific binding varied among tissues, the highest values being displayed by kidney membranes. In the liver, the binding of oPRL was not strongly displaced by tilapia prolactins (tPRL177 and tPRL188), although tPRL177 was six times more potent than tPRL188. On the other hand, in kidney and gill membranes, the two tPRLs were equipotent. Tilapia PRLs showed low potency in competing for oPRL-binding sites when pregnant rat liver membranes were utilized. Tilapia growth hormone (tGH) and human growth hormone (hGH) displaced 125 I-oPRL from liver as well as did tPRL177 but were not recognized well by renal or branchial receptors. Two 125 I-oPRL-binding sites were detected in every tissue tested. These binding sites are subject to physiological regulation since adaptation to seawater resulted in a significant decrease in specific binding

  20. Comparison of Plasma Neurosteroid and Prolactin Levels in Patients with Schizophrenia and Healthy Individuals

    Directory of Open Access Journals (Sweden)

    Forough Riahi

    2016-01-01

    Full Text Available Background. The present study aimed to compare plasma levels of cortisol, testosterone, dehydroepiandrosterone (DHEA, and prolactin in patients with schizophrenia and healthy individuals. Method. A total of 100 patients with schizophrenia disorder (69 men and 31 women and 190 healthy individuals (94 men and 96 women participated in this cross-sectional study. They were tested for hormone levels and completed demographic questionnaires. Data were analyzed using multivariate analysis of variance (MANOVA and one-way analysis of variance. Results. Serum testosterone level was significantly higher in men with schizophrenia than in healthy men. Women with schizophrenia had a significantly higher level of testosterone and lower level of prolactin compared to healthy women. There were no significant differences in hormone levels across various subtypes of schizophrenia. No significant differences also were observed in hormones levels in patients with first-episode schizophrenia disorder compared to those in patients with recurrent episodes. Conclusion. This study indicated that abnormal testosterone and prolactin levels might be associated with pathophysiology of schizophrenia disorder.

  1. Possible role of serum testosterone, gonadotropins and prolactin in patients with premature ejaculation.

    Science.gov (United States)

    Abu El-Hamd, M; Farah, A

    2018-02-01

    Premature ejaculation (PE) is the most common male sexual dysfunction. This study aimed to investigate the role of serum testosterone, gonadotropins and prolactin in patients with PE. In a prospective a case-controlled study, it was conducted on 90 male patients with PE and 90 male healthy participants as controls. Patients were evaluated by Premature Ejaculation Diagnostic Tool (PEDT) and intravaginal ejaculatory latency time (IELT). Patients with mean IELT values ≤60 s and PEDT total scores ≥11 were considered to have PE. Serum levels of total testosterone (TT), free testosterone (FT), follicle-stimulating hormone (FSH), luteinising hormone (LH) and prolactin (PL) were investigated in patients with PE and controls. There was no statistically significant difference between patients with PE and controls regarding the serum levels of TT, FT, FSH, LH and PL (p value ˃.05). There was no significant correlation between the sex hormones levels (TT, FT, FSH, LH and PL) and (age, body mass index (BMI), IELTS and total PEDT scores of the patients; p value ˃.05). This study concluded that there was no disturbance in serum levels of testosterone, gonadotropins and prolactin in patients with PE and controls. These hormones could not relate to pathogenesis of PE. © 2017 Blackwell Verlag GmbH.

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Science.gov (United States)

    Schmid, Baptiste; Chastel, Olivier; Jenni, Lukas

    2011-10-01

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

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

    Science.gov (United States)

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

    2016-06-01

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

  5. AKR1B10 induces cell resistance to daunorubicin and idarubicin by reducing C13 ketonic group

    International Nuclear Information System (INIS)

    Zhong Linlin; Shen Honglin; Huang Chenfei; Jing, Hongwu; Cao Deliang

    2011-01-01

    Daunorubicin, idarubicin, doxorubicin and epirubicin are anthracyclines widely used for the treatment of lymphoma, leukemia, and breast, lung, and liver cancers, but tumor resistance limits their clinical success. Aldo-keto reductase family 1 B10 (AKR1B10) is an NADPH-dependent enzyme overexpressed in liver and lung carcinomas. This study was aimed to determine the role of AKR1B10 in tumor resistance to anthracyclines. AKR1B10 activity toward anthracyclines was measured using recombinant protein. Cell resistance to anthracycline was determined by ectopic expression of AKR1B10 or inhibition by epalrestat. Results showed that AKR1B10 reduces C13-ketonic group on side chain of daunorubicin and idarubicin to hydroxyl forms. In vitro, AKR1B10 converted daunorubicin to daunorubicinol at V max of 837.42 ± 81.39 nmol/mg/min, K m of 9.317 ± 2.25 mM and k cat /K m of 3.24. AKR1B10 showed better catalytic efficiency toward idarubicin with V max at 460.23 ± 28.12 nmol/mg/min, K m at 0.461 ± 0.09 mM and k cat /K m at 35.94. AKR1B10 was less active toward doxorubicin and epirubicin with a C14-hydroxyl group. In living cells, AKR1B10 efficiently catalyzed reduction of daunorubicin (50 nM) and idarubicin (30 nM) to corresponding alcohols. Within 24 h, approximately 20 ± 2.7% of daunorubicin (1 μM) or 23 ± 2.3% of idarubicin (1 μM) was converted to daunorubicinol or idarubicinol in AKR1B10 expression cells compared to 7 ± 0.9% and 5 ± 1.5% in vector control. AKR1B10 expression led to cell resistance to daunorubicin and idarubicin, but inhibitor epalrestat showed a synergistic role with these agents. Together our data suggest that AKR1B10 participates in cellular metabolism of daunorubicin and idarubicin, resulting in drug resistance. These data are informative for the clinical use of idarubicin and daunorubicin. - Highlights: → This study defines enzyme activity of AKR1B10 protein towards daunorubicin, idarubicin, doxorubicin, and epirubicin. → This study pinpoints

  6. The involvement of prolactin in avian molt: the effects of gender and breeding success on the timing of molt in Mute swans (Cygnus olor).

    Science.gov (United States)

    Dawson, A; Perrins, C M; Sharp, P J; Wheeler, D; Groves, S

    2009-04-01

    The aim of the study was to test the hypothesis that decreasing plasma prolactin stimulates or permits the initiation of avian molt. Changes in the concentration of plasma prolactin in Mute swans (Cygnus olor) were compared in non-breeding singletons and breeding pairs. In breeding swans, the onset of molt is delayed compared to non-breeders, and is delayed further in breeding males compared to their female partners. The seasonal decrease in prolactin in non-breeding birds of both sexes started at the end of May and was associated with the initiation of molt 4 weeks later. The decrease in plasma prolactin in incubating females was more pronounced, as a consequence of increased prolactin secretion associated with incubation behavior, but also started at end of May, and was associated the onset of molt 6 weeks later. In breeding males, plasma prolactin increased at the end of May when they started to care for their newly hatched cygnets. Correspondingly, prolactin began to decrease 3-5 weeks later in males than in females. These males started to molt in mid August, at least 4 weeks later than females. It is concluded that molt is related to decreasing plasma prolactin, and is inhibited when plasma prolactin is increasing or high.

  7. TRMM Visible and Infrared Scanner Calibrated Radiances L1B 1.5 hours V7 (TRMM_1B01) at GES DISC

    Data.gov (United States)

    National Aeronautics and Space Administration — This TRMM Visible and Infrared Scanner (VIRS) Level 1B Calibrated Radiance Product (1B01) contains calibrated radiances and auxiliary geolocation information from...

  8. EFFECT OF MORINGA OLEIFERA ON LEVEL OF PROLACTIN AND BREAST MILK PRODUCTION IN POSTPARTUM MOTHERS

    Directory of Open Access Journals (Sweden)

    Yuni Sulistiawati

    2017-04-01

    Full Text Available Background: Breastfeeding among postpartum mothers has been a problem due to low milk supply. As a result, mothers often decide to give formula milk or other additional foods, which might affect to the infant’s growth and development. Objective: This study aims to investigate the effect of Moringa Oliefera on the levels of prolactin and breast milk production (baby’s weight and sleep duration in postpartum mothers. Methods: Quasi-Experimental study with Non Equivalent control group design. There were 30 respondents recruited by purposive sampling, consisted of 15 respondents in intervention group and 15 respondents in the control group. This study was conducted from November until December 2016 in Four Midwive Independent Practice (BPM in the working area of the Health Center of Tlogosari wetan Semarang. Data were analyzed using Independent t-test. Results: Findings showed that there was a mean difference of prolactin level in the intervention group (231.72 ng / ml, and the control group (152.75 ng / ml; and a significant effect on increasing the levels of prolactin (p = 0.002. The mean of baby’s weight in the intervention group was 3783.33 grams, and in the control group was 3599.00 grams. However, there was no significant effect of moringa oleifera on baby’s weight (p = 0.313> 0.05. While the mean difference on sleep duration was 128.20 minutes in the intervention group and 108.80 minutes in the control group. There was a significant effect on baby’s sleep duration (p= 0.000. Conclusion: There were significant effects of moringa oleifera on mother’s prolactin and sleep duration of the baby. However, there was no significant effect on baby’s weight. Thus, it can be suggested that moringa oleifera can be used as an alternative treatment to increase breast milk production and prolactin hormones. Midwives should promote the benefits of moringa leaves as one of alternative supplements.

  9. Four new neolignans isolated from Eleutherococcus senticosus and their protein tyrosine phosphatase 1B inhibitory activity (PTP1B).

    Science.gov (United States)

    Zhang, Le; Li, Ban-Ban; Li, Hao-Ze; Meng, Xiao; Lin, Xin; Jiang, Yi-Yu; Ahn, Jong-Seog; Cui, Long

    2017-09-01

    Four new compounds, erythro-7'E-4-hydroxy-3,3'-dimethoxy-8,5'-oxyneoligna-7'-ene-7,9-diol-9'-al (1), (7S,8S)-4-hydroxy-3,1',3'-trimethoxy-4',7-epoxy-8,5'-neolign-9-ol (5), (7S,8S,7'E)-5-hydroxy-3,3'-dimethoxy-4',7-epoxy-8,5'-neolign-7'-ene-9,9'-diol (6) and (7S,8S,7'E)-5-hydroxy-3,3',9'-trimethoxy-4'-7-epoxy-8,5'-neolign-7'-ene-9-ol (7). Along with four known compounds (2-4, 8) were isolated from the EtOAc-soluble extract of Eleutherococcus senticosus. Their structures were elucidated on the basis of spectroscopic and physicochemical analyses. All the compounds were evaluated for in vitro inhibitory activity against PTP1B, VHR and PP1. Among them, compounds 1-4 and 6-8 were found to exhibit selective inhibitory activity on PTP1B with IC 50 values ranging from 17.2±1.6 to 32.7±1.2μM. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. No variations in transit times for Qatar-1 b

    Science.gov (United States)

    Maciejewski, G.; Fernández, M.; Aceituno, F. J.; Ohlert, J.; Puchalski, D.; Dimitrov, D.; Seeliger, M.; Kitze, M.; Raetz, St.; Errmann, R.; Gilbert, H.; Pannicke, A.; Schmidt, J.-G.; Neuhäuser, R.

    2015-05-01

    Aims: The transiting hot-Jupiter planet Qatar-1 b exhibits variations in transit times that could be perturbative. A hot Jupiter with a planetary companion on a nearby orbit would constitute an unprecedented planetary configuration, which is important for theories of the formation and evolution of planetary systems. We performed a photometric follow-up campaign to confirm or refute transit timing variations. Methods: We extend the baseline of transit observations by acquiring 18 new transit light curves acquired with 0.6-2.0 m telescopes. These photometric time series, together with data available in the literature, were analyzed in a homogenous way to derive reliable transit parameters and their uncertainties. Results: We show that the dataset of transit times is consistent with a linear ephemeris leaving no hint of any periodic variations with a range of 1 min. We find no compelling evidence of a close-in planetary companion to Qatar-1 b. This finding is in line with a paradigm that hot Jupiters are not components of compact multiplanetary systems. Based on dynamical simulations, we place tighter constraints on the mass of any fictitious nearby planet in the system. Furthermore, new transit light curves allowed us to redetermine system parameters with better precision than reported in previous studies. Our values generally agree with previous determinations. Partly based on (1) data collected with telescopes at the Rozhen National Astronomical Observatory and (2) observations obtained with telescopes of the University Observatory Jena, which is operated by the Astrophysical Institute of the Friedrich-Schiller-University.Tables of light curve data are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/577/A109

  11. NGTS-1b: a hot Jupiter transiting an M-dwarf

    Science.gov (United States)

    Bayliss, Daniel; Gillen, Edward; Eigmüller, Philipp; McCormac, James; Alexander, Richard D.; Armstrong, David J.; Booth, Rachel S.; Bouchy, François; Burleigh, Matthew R.; Cabrera, Juan; Casewell, Sarah L.; Chaushev, Alexander; Chazelas, Bruno; Csizmadia, Szilard; Erikson, Anders; Faedi, Francesca; Foxell, Emma; Gänsicke, Boris T.; Goad, Michael R.; Grange, Andrew; Günther, Maximilian N.; Hodgkin, Simon T.; Jackman, James; Jenkins, James S.; Lambert, Gregory; Louden, Tom; Metrailler, Lionel; Moyano, Maximiliano; Pollacco, Don; Poppenhaeger, Katja; Queloz, Didier; Raddi, Roberto; Rauer, Heike; Raynard, Liam; Smith, Alexis M. S.; Soto, Maritza; Thompson, Andrew P. G.; Titz-Weider, Ruth; Udry, Stéphane; Walker, Simon R.; Watson, Christopher A.; West, Richard G.; Wheatley, Peter J.

    2018-04-01

    We present the discovery of NGTS-1b, a hot Jupiter transiting an early M-dwarf host (Teff,* = 3916 ^{+71}_{-63} K) in a P = 2.647 d orbit discovered as part of the Next Generation Transit Survey (NGTS). The planet has a mass of 0.812 ^{+0.066}_{-0.075} MJ, making it the most massive planet ever discovered transiting an M-dwarf. The radius of the planet is 1.33 ^{+0.61}_{-0.33} RJ. Since the transit is grazing, we determine this radius by modelling the data and placing a prior on the density from the population of known gas giant planets. NGTS-1b is the third transiting giant planet found around an M-dwarf, reinforcing the notion that close-in gas giants can form and migrate similar to the known population of hot Jupiters around solar-type stars. The host star shows no signs of activity, and the kinematics hint at the star being from the thick disc population. With a deep (2.5 per cent) transit around a K = 11.9 host, NGTS-1b will be a strong candidate to probe giant planet composition around M-dwarfs via James Webb Space Telescope transmission spectroscopy.

  12. HNF1B-associated clinical phenotypes: the kidney and beyond.

    Science.gov (United States)

    Bockenhauer, Detlef; Jaureguiberry, Graciana

    2016-05-01

    Mutations in HNF1B, the gene encoding hepatocyte nuclear factor 1β are the most commonly identified genetic cause of renal malformations. HNF1B was first identified as a disease gene for diabetes (MODY5) in 1997, and its involvement in renal disease was subsequently noted through clinical observations in pedigrees affected by MODY5. Since then, a whole spectrum of associated phenotypes have been reported, including genital malformations, autism, epilepsy, gout, hypomagnesaemia, primary hyperparathyroidism, liver and intestinal abnormalities and a rare form of kidney cancer. The most commonly identified mutation, in approximately 50 % of patients, is an entire gene deletion occurring in the context of a 17q12 chromosomal microdeletion that also includes several other genes. Some of the associated phenotypes, especially the neurologic ones, appear to occur only in the context of this microdeletion and thus may not be directly linked to HNF1B. Here we review the spectrum of associated phenotypes and discuss potential implications for clinical management.

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

    Science.gov (United States)

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

    2017-08-01

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

  14. De novo mutations in ARID1B associated with both syndromic and non-syndromic short stature.

    Science.gov (United States)

    Yu, Yongguo; Yao, RuEn; Wang, Lili; Fan, Yanjie; Huang, Xiaodong; Hirschhorn, Joel; Dauber, Andrew; Shen, Yiping

    2015-09-16

    Human height is a complex trait with a strong genetic basis. Recently, a significant association between rare copy number variations (CNVs) and short stature has been identified, and candidate genes in these rare CNVs are being explored. This study aims to evaluate the association between mutations in ARID1B gene and short stature, both the syndromic and non-syndromic form. Based on a case-control study of whole genome chromosome microarray analysis (CMA), three overlapping CNVs were identified in patients with developmental disorders who exhibited short stature. ARID1B, a causal gene for Coffin Siris syndrome, is the only gene encompassed by all three CNVs. A following retrospective genotype-phenotype analysis based on a literature review confirmed that short stature is a frequent feature in those Coffin-Siris syndrome patients with ARID1B mutations. Mutation screening of ARID1B coding regions was further conducted in a cohort of 48 non-syndromic short stature patients,andfour novel missense variants including two de novo mutations were found. These results suggest that haploinsufficient mutations of ARID1B are associated with syndromic short stature including Coffin-Siris syndrome and intellectual disability, while rare missense variants in ARID1B are associated with non-syndromic short stature. This study supports the notion that mutations in genes related to syndromic short stature may exert milder effect and contribute to short stature in the general population.

  15. Antimicrobial Resistance of Shigella flexneri Serotype 1b Isolates in China.

    Directory of Open Access Journals (Sweden)

    Xianyan Cui

    Full Text Available Shigella flexneri serotype 1b is among the most prominent serotypes in developing countries, followed by serotype 2a. However, only limited data is available on the global phenotypic and genotypic characteristics of S. flexneri 1b. In the present study, 40 S. flexneri 1b isolates from different regions of China were confirmed by serotyping and biochemical characterization. Antimicrobial susceptibility testing showed that 85% of these isolates were multidrug-resistant strains and antibiotic susceptibility profiles varied between geographical locations. Strains from Yunnan were far more resistant than those from Xinjiang, while only one strain from Shanghai was resistant to ceftazidime and aztreonam. Fifteen cephalosporin resistant isolates were identified in this study. ESBL genes (blaSHV, blaTEM, blaOXA, and blaCTX-M and ampC genes (blaMOX, blaFOX, blaMIR(ACT-1, blaDHA, blaCIT and blaACC were subsequently detected among the 15 isolates. The results showed that these strains were positive only for blaTEM, blaOXA, blaCTX-M, intI1, and intI2. Furthermore, pulsed-field gel electrophoresis (PFGE analysis showed that the 40 isolates formed different profiles, and the PFGE patterns of Xinjiang isolates were distinct from Yunnan and Shanghai isolates by one obvious, large, missing band. In summary, similarities in resistance patterns were observed in strains with the same PFGE pattern. Overall, the results supported the need for more prudent selection and use of antibiotics in China. We suggest that antibiotic susceptibility testing should be performed at the start of an outbreak, and antibiotic use should be restricted to severe Shigella cases, based on resistance pattern variations observed in different regions. The data obtained in the current study might help to develop a strategy for the treatment of infections caused by S. flexneri 1b in China.

  16. Down-regulated expression of the protein-tyrosine phosphatase 1B (PTP1B) is associated with aggressive clinicopathologic features and poor prognosis in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Zheng, Long-Yi; Zhou, Dong-Xun; Lu, Jin; Zhang, Wen-Jun; Zou, Da-Jin

    2012-01-01

    Highlights: ► PTP1B protein showed decreased expression in 67.79% of the HCC patients. ► Low PTP1B expression predicts poor prognosis of HCC. ► Low PTP1B expression is correlated with expansion of OV6 + tumor-initiating cells. ► Down-regulation of PTP1B is associated with activation of Wnt/β-Catenin signaling. -- Abstract: The protein-tyrosine phosphatase 1B (PTP1B) is a classical non-transmembrane protein tyrosine phosphatase that plays a key role in metabolic signaling and can exert both tumor suppressing and tumor promoting effects in different cancers depending on the substrate involved and the cellular context. However, the expression level and function of PTP1B in hepatocellular carcinoma (HCC) remain unclear. In this study, PTP1B expression was detected by immunohistochemistry in normal liver tissue (n = 16) and hepatocellular carcinoma (n = 169). The correlations between PTP1B expression level and clinicopathologic features and patient survival were also analyzed. One hundred and eleven of 169 HCC patients (65.7%) had negative or low PTP1B expression in tumorous tissues, whereas normal tissues always expressed strong PTP1B. Decreased PTP1B expression was significantly associated with aggressive clinicopathologic features and poor prognosis. Immunohistochemistry also showed that low PTP1B expression level was correlated with high percentage of OV6 + tumor-initiating cells (T-ICs) and high frequency of nuclear β-Catenin expression in HCC specimens. Our findings demonstrate for the first time that the loss of inhibitory effect of PTP1B may contribute to progression and invasion of HCC through activation of Wnt/β-Catenin signaling and expansion of liver T-ICs. PTP1B may serve as a valuable prognostic biomarker and potential therapeutic target in HCC.

  17. Down-regulated expression of the protein-tyrosine phosphatase 1B (PTP1B) is associated with aggressive clinicopathologic features and poor prognosis in hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Long-Yi [Department of Endocrinology, Changhai Hospital, 168 Changhai Road, Shanghai 200433 (China); Zhou, Dong-Xun [Department of Comprehensive Treatment II, Eastern Hepatobiliary Surgery Hospital, 225 Changhai Road, Shanghai 200438 (China); Lu, Jin [Department of Endocrinology, Changhai Hospital, 168 Changhai Road, Shanghai 200433 (China); Zhang, Wen-Jun [Department of Emergency, Changhai Hospital, 168 Changhai Road, Shanghai 200433 (China); Zou, Da-Jin, E-mail: dajinzou@hotmail.com [Department of Endocrinology, Changhai Hospital, 168 Changhai Road, Shanghai 200433 (China)

    2012-04-13

    Highlights: Black-Right-Pointing-Pointer PTP1B protein showed decreased expression in 67.79% of the HCC patients. Black-Right-Pointing-Pointer Low PTP1B expression predicts poor prognosis of HCC. Black-Right-Pointing-Pointer Low PTP1B expression is correlated with expansion of OV6{sup +} tumor-initiating cells. Black-Right-Pointing-Pointer Down-regulation of PTP1B is associated with activation of Wnt/{beta}-Catenin signaling. -- Abstract: The protein-tyrosine phosphatase 1B (PTP1B) is a classical non-transmembrane protein tyrosine phosphatase that plays a key role in metabolic signaling and can exert both tumor suppressing and tumor promoting effects in different cancers depending on the substrate involved and the cellular context. However, the expression level and function of PTP1B in hepatocellular carcinoma (HCC) remain unclear. In this study, PTP1B expression was detected by immunohistochemistry in normal liver tissue (n = 16) and hepatocellular carcinoma (n = 169). The correlations between PTP1B expression level and clinicopathologic features and patient survival were also analyzed. One hundred and eleven of 169 HCC patients (65.7%) had negative or low PTP1B expression in tumorous tissues, whereas normal tissues always expressed strong PTP1B. Decreased PTP1B expression was significantly associated with aggressive clinicopathologic features and poor prognosis. Immunohistochemistry also showed that low PTP1B expression level was correlated with high percentage of OV6{sup +} tumor-initiating cells (T-ICs) and high frequency of nuclear {beta}-Catenin expression in HCC specimens. Our findings demonstrate for the first time that the loss of inhibitory effect of PTP1B may contribute to progression and invasion of HCC through activation of Wnt/{beta}-Catenin signaling and expansion of liver T-ICs. PTP1B may serve as a valuable prognostic biomarker and potential therapeutic target in HCC.

  18. Four Years of Real-Time GRB Followup by BOOTES-1B (2005–2008

    Directory of Open Access Journals (Sweden)

    Martin Jelínek

    2010-01-01

    Full Text Available Four years of BOOTES-1B GRB follow-up history are summarised for the first time in the form of a table. The successfully followed events are described case by case. Further, the data are used to show the GRB trigger rate in Spain on a per-year basis, resulting in an estimate of 18 triggers and about 51 hours of telescope time per year for real-time triggers. These numbers grow to about 22 triggers and 77 hours per year if we include also the GRBs observable within 2 hours after the trigger.

  19. Inhibition of Protein Tyrosine Phosphatase 1B by Aurintricarboxylic Acid and Methylenedisalicylic Acid: Polymer versus Monomer

    International Nuclear Information System (INIS)

    Shrestha, Suja; Lee, Keun Hyeung; Cho, Hyeong Jin

    2004-01-01

    In this study, we examined whether the in vitro inhibitory activity of ATA against PTPases resides in the monomer or high molecular weight components. Not to mention commercial ATA, the ATA sample synthesized according to the method previously reported to produce monomer was also found to contain polymeric materials as described below. Therefore, monomeric component of ATA was prepared absolutely free of polymer. Also synthesized in a pure form was methylenedisalicylic acid (MDSA), one of the low molecular weight components formed in the conventional preparation of ATA. Commercial MDSA was also proved to contain polymeric substances. The inhibitory potency of ATA and MDSA synthesized in a polymer-free form was evaluated against human protein tyrosine phosphatase 1B (PTP1B). Commercial ATA, however, contains significant amounts of polymeric materials schematically represented as. In general, ATA is prepared by condensation of salicylic acid with formaldehyde and the branching reaction results in the formation of polymers of molecular weights up to several thousands Dalton

  20. A Significant Role of the Truncated Ghrelin Receptor GHS-R1b in Ghrelin-induced Signaling in Neurons.

    Science.gov (United States)

    Navarro, Gemma; Aguinaga, David; Angelats, Edgar; Medrano, Mireia; Moreno, Estefanía; Mallol, Josefa; Cortés, Antonio; Canela, Enric I; Casadó, Vicent; McCormick, Peter J; Lluís, Carme; Ferré, Sergi

    2016-06-17

    The truncated non-signaling ghrelin receptor growth hormone secretagogue R1b (GHS-R1b) has been suggested to simply exert a dominant negative role in the trafficking and signaling of the full and functional ghrelin receptor GHS-R1a. Here we reveal a more complex modulatory role of GHS-R1b. Differential co-expression of GHS-R1a and GHS-R1b, both in HEK-293T cells and in striatal and hippocampal neurons in culture, demonstrates that GHS-R1b acts as a dual modulator of GHS-R1a function: low relative GHS-R1b expression potentiates and high relative GHS-R1b expression inhibits GHS-R1a function by facilitating GHS-R1a trafficking to the plasma membrane and by exerting a negative allosteric effect on GHS-R1a signaling, respectively. We found a preferential Gi/o coupling of the GHS-R1a-GHS-R1b complex in HEK-293T cells and, unexpectedly, a preferential Gs/olf coupling in both striatal and hippocampal neurons in culture. A dopamine D1 receptor (D1R) antagonist blocked ghrelin-induced cAMP accumulation in striatal but not hippocampal neurons, indicating the involvement of D1R in the striatal GHS-R1a-Gs/olf coupling. Experiments in HEK-293T cells demonstrated that D1R co-expression promotes a switch in GHS-R1a-G protein coupling from Gi/o to Gs/olf, but only upon co-expression of GHS-R1b. Furthermore, resonance energy transfer experiments showed that D1R interacts with GHS-R1a, but only in the presence of GHS-R1b. Therefore, GHS-R1b not only determines the efficacy of ghrelin-induced GHS-R1a-mediated signaling but also determines the ability of GHS-R1a to form oligomeric complexes with other receptors, promoting profound qualitative changes in ghrelin-induced signaling. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. A Significant Role of the Truncated Ghrelin Receptor GHS-R1b in Ghrelin-induced Signaling in Neurons*

    Science.gov (United States)

    Navarro, Gemma; Aguinaga, David; Angelats, Edgar; Medrano, Mireia; Moreno, Estefanía; Mallol, Josefa; Cortés, Antonio; Canela, Enric I.; Casadó, Vicent; McCormick, Peter J.; Lluís, Carme; Ferré, Sergi

    2016-01-01

    The truncated non-signaling ghrelin receptor growth hormone secretagogue R1b (GHS-R1b) has been suggested to simply exert a dominant negative role in the trafficking and signaling of the full and functional ghrelin receptor GHS-R1a. Here we reveal a more complex modulatory role of GHS-R1b. Differential co-expression of GHS-R1a and GHS-R1b, both in HEK-293T cells and in striatal and hippocampal neurons in culture, demonstrates that GHS-R1b acts as a dual modulator of GHS-R1a function: low relative GHS-R1b expression potentiates and high relative GHS-R1b expression inhibits GHS-R1a function by facilitating GHS-R1a trafficking to the plasma membrane and by exerting a negative allosteric effect on GHS-R1a signaling, respectively. We found a preferential Gi/o coupling of the GHS-R1a-GHS-R1b complex in HEK-293T cells and, unexpectedly, a preferential Gs/olf coupling in both striatal and hippocampal neurons in culture. A dopamine D1 receptor (D1R) antagonist blocked ghrelin-induced cAMP accumulation in striatal but not hippocampal neurons, indicating the involvement of D1R in the striatal GHS-R1a-Gs/olf coupling. Experiments in HEK-293T cells demonstrated that D1R co-expression promotes a switch in GHS-R1a-G protein coupling from Gi/o to Gs/olf, but only upon co-expression of GHS-R1b. Furthermore, resonance energy transfer experiments showed that D1R interacts with GHS-R1a, but only in the presence of GHS-R1b. Therefore, GHS-R1b not only determines the efficacy of ghrelin-induced GHS-R1a-mediated signaling but also determines the ability of GHS-R1a to form oligomeric complexes with other receptors, promoting profound qualitative changes in ghrelin-induced signaling. PMID:27129257

  2. Cortisol and prolactin concentrations during repeated blood sample collection from freely moving, mouse-sized mammals (Phodopus spp.).

    Science.gov (United States)

    Reburn, C J; Wynne-Edwards, K E

    2000-04-01

    Validation of a method for obtaining blood samples that does not change cortisol or prolactin concentrations yet allows serial blood samples to be collected from animals under anesthesia, without prior handling, from freely interacting social groups of small mammals. Results from five experiments are reported. Male dwarf hamsters (Phodopus spp.) were housed in modified home cages under continuous flow of compressed air that could be switched to isoflurane in O2 vehicle without approaching the cages. Dwarf hamsters respond to manual restraint with behavioral distress and increase in the concentration of the dominant glucocorticoid, cortisol, and decrease in prolactin concentration. Both effects are evident within one minute. In contrast, when this new method was used, neither cortisol nor prolactin changed in response to repeated sample collection (up to 8 successive samples at 2 hour intervals), prolonged isoflurane exposure, or substantial blood volume reduction (30%). Prolactin concentration was suppressed and cortisol concentration was increased in response to stimuli from other hamsters tested without anesthesia. Suppression of prolactin concentration was graded in response to the degree of stress and equaled the pharmacologic reduction caused by bromocryptine mesylate (50 microg of CB154 x 3 days). The technique is superior to alternatives for studies of behavioral endocrinology of freely interacting small mammals.

  3. Attenuated stress response to acute restraint and forced swimming stress in arginine vasopressin 1b receptor subtype (Avpr1b) receptor knockout mice and wild-type mice treated with a novel Avpr1b receptor antagonist.

    Science.gov (United States)

    Roper, J A; Craighead, M; O'Carroll, A-M; Lolait, S J

    2010-11-01

    Arginine vasopressin (AVP) synthesised in the parvocellular region of the hypothalamic paraventricular nucleus and released into the pituitary portal vessels acts on the 1b receptor subtype (Avpr1b) present in anterior pituitary corticotrophs to modulate the release of adrenocorticotrophic hormone (ACTH). Corticotrophin-releasing hormone is considered the major drive behind ACTH release; however, its action is augmented synergistically by AVP. To determine the extent of vasopressinergic influence in the hypothalamic-pituitary-adrenal axis response to restraint and forced swimming stress, we compared the stress hormone levels [plasma ACTH in both stressors and corticosterone (CORT) in restraint stress only] following acute stress in mutant Avpr1b knockout (KO) mice compared to their wild-type controls following the administration of a novel Avpr1b antagonist. Restraint and forced swimming stress-induced increases in plasma ACTH were significantly diminished in mice lacking a functional Avpr1b and in wild-type mice that had been pre-treated with Avpr1b antagonist. A corresponding decrease in plasma CORT levels was also observed in acute restraint-stressed knockout male mice, and in Avpr1b-antagonist-treated male wild-type mice. By contrast, plasma CORT levels were not reduced in acutely restraint-stressed female knockout animals, or in female wild-type animals pre-treated with Avpr1b antagonist. These results demonstrate that pharmacological antagonism or inactivation of Avpr1b causes a reduction in the hypothalamic-pituitary-adrenal (HPA) axis response, particularly ACTH, to acute restraint and forced swimming stress, and show that Avpr1b knockout mice constitute a model by which to study the contribution of Avpr1b to the HPA axis response to acute stressors. © 2010 The Authors. Journal of Neuroendocrinology © 2010 Blackwell Publishing Ltd.

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

    International Nuclear Information System (INIS)

    Chang, Y.S.

    1985-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Jakob Triebel

    2017-11-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-04-22

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

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

    International Nuclear Information System (INIS)

    Camoratto, A.M.

    1988-01-01

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

  8. EOS MLS Level 1B Data Processing Software. Version 3

    Science.gov (United States)

    Perun, Vincent S.; Jarnot, Robert F.; Wagner, Paul A.; Cofield, Richard E., IV; Nguyen, Honghanh T.; Vuu, Christina

    2011-01-01

    This software is an improvement on Version 2, which was described in EOS MLS Level 1B Data Processing, Version 2.2, NASA Tech Briefs, Vol. 33, No. 5 (May 2009), p. 34. It accepts the EOS MLS Level 0 science/engineering data, and the EOS Aura spacecraft ephemeris/attitude data, and produces calibrated instrument radiances and associated engineering and diagnostic data. This version makes the code more robust, improves calibration, provides more diagnostics outputs, defines the Galactic core more finely, and fixes the equator crossing. The Level 1 processing software manages several different tasks. It qualifies each data quantity using instrument configuration and checksum data, as well as data transmission quality flags. Statistical tests are applied for data quality and reasonableness. The instrument engineering data (e.g., voltages, currents, temperatures, and encoder angles) is calibrated by the software, and the filter channel space reference measurements are interpolated onto the times of each limb measurement with the interpolates being differenced from the measurements. Filter channel calibration target measurements are interpolated onto the times of each limb measurement, and are used to compute radiometric gain. The total signal power is determined and analyzed by each digital autocorrelator spectrometer (DACS) during each data integration. The software converts each DACS data integration from an autocorrelation measurement in the time domain into a spectral measurement in the frequency domain, and estimates separately the spectrally, smoothly varying and spectrally averaged components of the limb port signal arising from antenna emission and scattering effects. Limb radiances are also calibrated.

  9. Pregnancy and pregnancy outcome in hepatitis C type 1b.

    LENUS (Irish Health Repository)

    Jabeen, T

    2012-02-03

    A large cohort of rhesus-negative women in Ireland were inadvertently infected with hepatitis C virus following exposure to contaminated anti-D immunoglobulin in 1977-8. This major iatrogenic episode was discovered in 1994. We studied 36 women who had been infected after their first pregnancy, and compared them to an age- and parity-matched control group of rhesus-positive women. The presence of hepatitis C antibody was confirmed in all 36 by enzyme-linked immunosorbent assay and by recombinant immunoblot assay, while 26 (72%) of the cohort were HCV-RNA-positive (type 1b) on PCR testing. In the 20 years post-infection, all members of the study group had at least one pregnancy, and mean parity was 3.5. They had a total of 100 pregnancies and 85 of these went to term. There were four premature births, one being a twin pregnancy, and 11 spontaneous miscarriages. One miscarriage occurred in the pregnancy following HCV infection. There were two neonatal deaths due to severe congenital abnormalities in the PCR-positive women. Of the children born to HCV-RNA positive mothers, only one (2.3%) tested positive for the virus. Significant portal fibrosis on liver biopsy was confined to HCV-RNA-positive mothers apart from one single exception in the antibody-positive HCV-RNA-negative group. Comparison with the control group showed no increase in spontaneous miscarriage rate, and no significant difference in obstetric complications; birth weights were similar for the two groups.

  10. Concentrations of testosterone, luteal hormone and prolactin in the serum as well as comparisons of sensitivity between radioimmunoassays and enzyme assays for the detection of acid prostate phosphatase in the presence of carcinomas of the prostate

    International Nuclear Information System (INIS)

    Vopelius-Feldt, F. von.

    1986-01-01

    The relationship between carcinomas of the prostate and the plasma levels of testosterone, luteal hormone and prolactin as well as the possible influence of these neoplasms on the testosterone binding capacity and free testosterone index are investigated for various tumour stages and degrees of histological differentiation, in connection with several forms of local therapy as well as a variety of contrasexual methods. The sensitivity of enzyme assays and radioimmunoassays for the detection of acid prostate phosphatase is evaluated within the framework of this study. (MBL) [de

  11. Changes of serum prolactin level in patients with oral cavity squamous cell carcinoma

    International Nuclear Information System (INIS)

    Zheng Jian; Li Hairu; Chen Yaming; Tang Guihong; Xu Yalan

    2004-01-01

    To investigate the change of serum prolactin (PRL) level in patients with oral cavity squamous cell carcinoma, serum PRL level in 79 normal person and 68 cases of patient s was measured by RIA. The result showed that serum PRL level was significantly higher in 26 patients (38.2%, 26/68) than that in the control (P 0.05) between the sex and region of lesion. The above results indicated that proportion of patient with oral cavity squamous cell carcinoma was hyperprolactinaemia and the change of PRL was related to the development in oral cavity squamous cell carcinoma. (authors)

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

    Science.gov (United States)

    Pal, Shyamali

    2017-12-01

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

  13. Tuning the brain for motherhood: prolactin-like central signalling in virgin, pregnant, and lactating female mice.

    Science.gov (United States)

    Salais-López, Hugo; Lanuza, Enrique; Agustín-Pavón, Carmen; Martínez-García, Fernando

    2017-03-01

    Prolactin is fundamental for the expression of maternal behaviour. In virgin female rats, prolactin administered upon steroid hormone priming accelerates the onset of maternal care. By contrast, the role of prolactin in mice maternal behaviour remains unclear. This study aims at characterizing central prolactin activity patterns in female mice and their variation through pregnancy and lactation. This was revealed by immunoreactivity of phosphorylated (active) signal transducer and activator of transcription 5 (pSTAT5-ir), a key molecule in the signalling cascade of prolactin receptors. We also evaluated non-hypophyseal lactogenic activity during pregnancy by administering bromocriptine, which suppresses hypophyseal prolactin release. Late-pregnant and lactating females showed significantly increased pSTAT5-ir resulting in a widespread pattern of immunostaining with minor variations between pregnant and lactating animals, which comprises nuclei of the sociosexual and maternal brain, including telencephalic (septum, nucleus of the stria terminalis, and amygdala), hypothalamic (preoptic, paraventricular, supraoptic, and ventromedial), and midbrain (periaqueductal grey) regions. During late pregnancy, this pattern was not affected by the administration of bromocriptine, suggesting it to be elicited mostly by non-hypophyseal lactogenic agents, likely placental lactogens. Virgin females displayed, instead, a variable pattern of pSTAT5-ir restricted to a subset of the brain nuclei labelled in pregnant and lactating mice. A hormonal substitution experiment confirmed that estradiol and progesterone contribute to the variability found in virgin females. Our results reflect how the shaping of the maternal brain takes place prior to parturition and suggest that lactogenic agents are important candidates in the development of maternal behaviours already during pregnancy.

  14. A P387L variant in protein tyrosine phosphatase-1B (PTP-1B) is associated with type 2 diabetes and impaired serine phosphorylation of PTP-1B in vitro

    DEFF Research Database (Denmark)

    Echwald, Søren M; Riis, Helle Bach; Vestergaard, Henrik

    2002-01-01

    In the present study, we tested the hypothesis that variability in the protein tyrosine phosphatase-1B (PTP-1B) gene is associated with type 2 diabetes. Using single-strand conformational polymorphism analysis, we examined cDNA of PTP-1B from 56 insulin-resistant patients with type 2 diabetes.......0012). In summary, a rare P387L variant of the PTP-1B gene is associated with a 3.7 (CI 1.26-10.93, P = 0.02) genotype relative risk of type 2 diabetes in the examined population of Danish Caucasian subjects and results in impaired in vitro serine phosphorylation of the PTP-1B peptide....

  15. Prolactin-secreting adenoma as part of the multiple endocrine neoplasia--type I (MEN-I) syndrome.

    Science.gov (United States)

    Levine, J H; Sagel, J; Rosebrock, G; Gonzalez, J J; Nair, R; Rawe, S; Powers, J M

    1979-06-01

    Two patients presented with the galactorrhea-amenorrhea syndrome. One patient had previously had parathyroid hyperplasia and the other an insulinoma. Preoperative evaluation of each patient revealed hyperprolactinemia and radiological evidence of an abnormal sella turcica. Pituitary adenomas were identified and removed at surgery. Immunostaining techniques confirmed the presence of prolactin-containing cells in both tumors. We propose that prolactin-secreting tumors be considered as part of the MEN-I syndrome, and that patients presenting with the galactorrhea-amenorrhea syndrome be screened and followed sequentially for evidence of other endocrine neoplasia.

  16. Alcohol dehydrogenase-1B genotype (rs1229984) is a strong determinant of the relationship between body weight and alcohol intake in Japanese alcoholic men.

    Science.gov (United States)

    Yokoyama, Akira; Yokoyama, Tetsuji; Matsui, Toshifumi; Mizukami, Takeshi; Matsushita, Sachio; Higuchi, Susumu; Maruyama, Katsuya

    2013-07-01

    The calories in alcoholic beverages consumed by alcoholics are a major energy source and a strong modifier of their body weight. Genetic polymorphisms of alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) affect susceptibility to alcoholism and may affect body weight via gene-associated differences in fuel utilization in alcoholics. We evaluated associations between ADH1B/ALDH2 genotypes and the body weight and body mass index (BMI) of 1,301 Japanese alcoholic men at the time of their first visit to an addiction center. Median (25th to 75th) caloric intake in the form of alcoholic beverages was 864 (588 to 1,176) kcal/d. Age-adjusted caloric intake did not differ according to ADH1B/ALDH2 genotypes. The body weight and BMI values showed that the ADH1B*2/*2 and *1/*2 carriers (n = 939) were significantly leaner than the ADH1B*1/*1 carriers (n = 362) irrespective of age, drinking, smoking, and dietary habits. The age-adjusted body weight values of the ADH1B*2/*2, ADH1B*1/*2, and ADH1B*1/*1 carriers were 58.4 ± 0.4, 58.7 ± 0.5, and 63.6 ± 0.5 kg, respectively (ADH1B*2 vs. ADH1B*1/*1 carriers, p strong determinant of body weight in the alcoholics. The more rapid EtOH elimination associated with the ADH1B*2 allele may result in less efficient utilization of EtOH as an energy source in alcoholics. Copyright © 2013 by the Research Society on Alcoholism.

  17. Residue 259 in protein-tyrosine phosphatase PTP1B and PTPα determines the flexibility of glutamine 262

    DEFF Research Database (Denmark)

    Peters, Günther H.j.; Iversen, L.F.; Andersen, H.S.

    2004-01-01

    To study the flexibility of the substrate-binding site and in particular of Gln262, we have performed adiabatic conformational search and molecular dynamics simulations on the crystal structure of the catalytic domain of wild-type protein-tyrosine phosphatase (PTP) 1B, a mutant PTP1B(R47V),(D48N...... and second step of the phosphate hydrolysis. Analyses of the trajectories revealed that in the cysteine-phosphor complex of PTP1B, Gln262 oscillates freely between the bound phosphate group and Gly259 frequently forming, as observed in the crystal structure, a hydrogen bond with the backbone oxygen of Gly259...... around Gln262 and the active site Cys215 reveals that the probability of finding a water molecule correctly positioned for catalysis is much larger in PTP1B than in PTP1B(R47V),(D48N),(M258C),(G259Q) and PTPalpha, in accordance with experiments....

  18. Association between the IL1B (-511), IL1B (+3954), IL1RN (VNTR) polymorphisms and Graves' disease risk: a meta-analysis of 11 case-control studies.

    Science.gov (United States)

    Chen, Min-Li; Liao, Ning; Zhao, Hua; Huang, Jian; Xie, Zheng-Fu

    2014-01-01

    Data on the association between the interleukin-1 (IL-1) gene polymorphisms and Graves' disease (GD) risk were conflicting. A meta-analysis was undertaken to assess this association. We searched for case-control studies investigating the association between the IL1B (-511), IL1B (+3954), IL1RN (VNTR) polymorphisms and GD risk. We extracted data using standardized forms and calculated odds ratios (OR) with 95% confidence intervals (CI). A total of 11 case-control studies were included in this meta-analysis. Available data indicated that the IL1B (-511) polymorphism was associated with GD risk in the overall populations (Caucasians and Asians) in homozygote model (TT vs. CC, OR = 0.86, 95% CI: 0.76-0.97, Pz  = 0.015), but not in dominant and recessive models (TT+TC vs. CC: OR = 0.95, 95% CI: 0.81-1.12, Pz  =  0.553 and TT vs. TC+CC: OR = 0.82, 95% CI: 0.60-1.12, Pz  =  0.205, respectively). No association between the IL1B (+3954), IL1RN (VNTR) polymorphisms and GD risk was found in the overall populations in any of the genetic models. In subgroup analyses according to ethnicity, the IL1B (-511) polymorphism was associated with GD risk in Asians in recessive and homozygote models (TT vs. TC+CC: OR =  0.68, 95% CI: 0.55-0.84, Pz VNTR) polymorphisms and GD risk was indicated in Asians, and we found no association between the IL1B (-511), IL1B (+3954), IL1RN (VNTR) polymorphisms and GD risk in Caucasians in any of the genetic models. The IL1B (-511) polymorphism, but not the IL1B (+3954) and IL1RN (VNTR) polymorphisms was associated with GD risk in Asians. There was no association between these polymorphisms and GD risk in Caucasians.

  19. Effects of cortisol, growth hormone and prolactin on gill claudin expression in Atlantic salmon

    DEFF Research Database (Denmark)

    Tipsmark, Christian Kølbæk; Jørgensen, Charlotte; Brande-Lavridsen, Nanna

    2009-01-01

    We recently showed that a series of tight junction proteins of the claudin family are regulated in the gill of salmon during salinity acclimation. The aim of the present study was to investigate the role of cortisol, growth hormone (GH) and prolactin (PRL) on regulation of expression of these iso......We recently showed that a series of tight junction proteins of the claudin family are regulated in the gill of salmon during salinity acclimation. The aim of the present study was to investigate the role of cortisol, growth hormone (GH) and prolactin (PRL) on regulation of expression...... antagonists RU486 and spironolactone, respectively. The observed in vitro responses were blocked by RU486, suggesting the involvement of a glucocorticoid type receptor. Injections of FW salmon with cortisol increased the expression of claudin 10e, 27a, and 30 but did not affect claudin 28a and 28b...... significantly. While GH had no effect on its own, the combination of GH and cortisol reduced claudin 28b levels. Injection of SW salmon with PRL selectively increased the expression of claudin 28a but had no effect on the other examined isoforms. The data shows that FW- (27a and 30) and SW-induced (10e...

  20. Convergent Evolution of Slick Coat in Cattle through Truncation Mutations in the Prolactin Receptor

    Directory of Open Access Journals (Sweden)

    Laercio R. Porto-Neto

    2018-02-01

    Full Text Available Evolutionary adaptations are occasionally convergent solutions to the same problem. A mutation contributing to a heat tolerance adaptation in Senepol cattle, a New World breed of mostly European descent, results in the distinct phenotype known as slick, where an animal has shorter hair and lower follicle density across its coat than wild type animals. The causal variant, located in the 11th exon of prolactin receptor, produces a frameshift that results in a truncated protein. However, this mutation does not explain all cases of slick coats found in criollo breeds. Here, we obtained genome sequences from slick cattle of a geographically distinct criollo breed, namely Limonero, whose ancestors were originally brought to the Americas by the Spanish. These data were used to identify new causal alleles in the 11th exon of the prolactin receptor, two of which also encode shortened proteins that remove a highly conserved tyrosine residue. These new mutations explained almost 90% of investigated cases of animals that had slick coats, but which also did not carry the Senepol slick allele. These results demonstrate convergent evolution at the molecular level in a trait important to the adaptation of an animal to its environment.

  1. Pituitary Androgen Receptor Signalling Regulates Prolactin but Not Gonadotrophins in the Male Mouse

    Science.gov (United States)

    O’Hara, Laura; Curley, Michael; Tedim Ferreira, Maria; Cruickshanks, Lyndsey; Milne, Laura; Smith, Lee B.

    2015-01-01

    Production of the androgen testosterone is controlled by a negative feedback loop within the hypothalamic-pituitary-gonadal (HPG) axis. Stimulation of testicular Leydig cells by pituitary luteinising hormone (LH) is under the control of hypothalamic gonadotrophin releasing hormone (GnRH), while suppression of LH secretion by the pituitary is controlled by circulating testosterone. Exactly how androgens exert their feedback control of gonadotrophin secretion (and whether this is at the level of the pituitary), as well as the role of AR in other pituitary cell types remains unclear. To investigate these questions, we exploited a transgenic mouse line (Foxg1Cre/+; ARfl/y) which lacks androgen receptor in the pituitary gland. Both circulating testosterone and gonadotrophins are unchanged in adulthood, demonstrating that AR signalling is dispensable in the male mouse pituitary for testosterone-dependent regulation of LH secretion. In contrast, Foxg1Cre/+; ARfl/y males have a significant increase in circulating prolactin, suggesting that, rather than controlling gonadotrophins, AR-signalling in the pituitary acts to suppress aberrant prolactin production in males. PMID:25799562

  2. Protein Phosphotyrosine Phosphatase 1B (PTP1B) in Calpain-dependent Feedback Regulation of Vascular Endothelial Growth Factor Receptor (VEGFR2) in Endothelial Cells

    Science.gov (United States)

    Zhang, Yixuan; Li, Qiang; Youn, Ji Youn; Cai, Hua

    2017-01-01

    The VEGF/VEGFR2/Akt/eNOS/NO pathway is essential to VEGF-induced angiogenesis. We have previously discovered a novel role of calpain in mediating VEGF-induced PI3K/AMPK/Akt/eNOS activation through Ezrin. Here, we sought to identify possible feedback regulation of VEGFR2 by calpain via its substrate protein phosphotyrosine phosphatase 1B (PTP1B), and the relevance of this pathway to VEGF-induced angiogenesis, especially in diabetic wound healing. Overexpression of PTP1B inhibited VEGF-induced VEGFR2 and Akt phosphorylation in bovine aortic endothelial cells, while PTP1B siRNA increased both, implicating negative regulation of VEGFR2 by PTP1B. Calpain inhibitor ALLN induced VEGFR2 activation, which can be completely blocked by PTP1B overexpression. Calpain activation induced by overexpression or Ca/A23187 resulted in PTP1B cleavage, which can be blocked by ALLN. Moreover, calpain activation inhibited VEGF-induced VEGFR2 phosphorylation, which can be restored by PTP1B siRNA. These data implicate calpain/PTP1B negative feedback regulation of VEGFR2, in addition to the primary signaling pathway of VEGF/VEGFR2/calpain/PI3K/AMPK/Akt/eNOS. We next examined a potential role of PTP1B in VEGF-induced angiogenesis. Endothelial cells transfected with PTP1B siRNA showed faster wound closure in response to VEGF. Aortic discs isolated from PTP1B siRNA-transfected mice also had augmented endothelial outgrowth. Importantly, PTP1B inhibition and/or calpain overexpression significantly accelerated wound healing in STZ-induced diabetic mice. In conclusion, our data for the first time demonstrate a calpain/PTP1B/VEGFR2 negative feedback loop in the regulation of VEGF-induced angiogenesis. Modulation of local PTP1B and/or calpain activities may prove beneficial in the treatment of impaired wound healing in diabetes. PMID:27872190

  3. Morpho-toxicology of chlorpyrifos to prolactin cells of a freshwater catfish, Heteropneustes fossilis =Morpho-toxicology of chlorpyrifos to prolactin cells of a freshwater catfish, Heteropneustes fossilis

    Directory of Open Access Journals (Sweden)

    Diwakar Mishra

    2012-10-01

    Full Text Available In the present study, an organophosphorus compound Coroban (active ingredient chlorpyrifos – E.C. 20% was used. In short-term exposure the fish were subjected to 0.8 of 96h LC50 value of chlorpyrifos (1.76 mg L-1 for 96h. In long-term exposure the experiment was performed for 28 days by using 0.2 of 96h LC50 value of chlorpyrifos (0.44 mg L-1. Fish were killed on each time intervals from control and experimental (chlorpyrifos groups after 24, 48, 72, and 96h in short-term exposure and after 7, 14, 21, and 28 days in long-term experiment. Blood samples were collected and sera were analyzed for calcium. Pituitary glands were fixed for histological studies and stained with Herlant tetrachrome and Heidenhain’s azan techniques. Short-term exposure of chlorpyrifos caused decrease in the serum calcium levels. No change was noticed in the prolactin cells of chlorpyrifos treated fish. Long-term treatment with chlorpyrifos provoked hypocalcemia. The prolactin cells of treated fish exhibited slight degranulation after 21 days whereas the nuclear volume remained unchanged. After 28 days, the prolactin cells exhibited further degranulation and the nuclear volume recorded an increase. Cytolysis and vacuolization were also visible. No estudo presente, o composto organofosforo Coroban (ingrediente ativo clorpirifo – E.C. 20% foi usado. Na exposição a curto prazo os peixes foram submetido a 0,8 de valor LC50 de 96h de clorpirifo (1,76 mg L-1 durante 96h. Na exposição a longo prazo o experimento foi executado durante 28 dias usando 0,2 de valor LC50 de 96h de clorpirifos (0,44 mg L-1. Os peixes foram mortos a cada intervalo dos grupos controle e experimental (clorpirifos após 24, 48, 72, e 96h em exposição a curto prazo e após 7, 14, 21, e 28 dias no experimento a longo prazo. As amostras de sangue foram colhidas e o soro foi analisado para cálcio. As glândulas pituitárias foram fixadas para estudos histológicos e colorido por tetracromo de

  4. 20 CFR 655.705 - What Federal agencies are involved in the H-1B and H-1B1 programs, and what are the...

    Science.gov (United States)

    2010-04-01

    ... Employers Seeking To Employ Nonimmigrants on H-1b Visas in Specialty Occupations and as Fashion Models, and... whether the individual is a fashion model of distinguished merit and ability, and whether the... § 655.700(d)(4). Each employer seeking an H-1B nonimmigrant in a specialty occupation or as a fashion...

  5. Phosphodiesterase-1b (Pde1b) knockout mice are resistant to forced swim and tail suspension induced immobility and show upregulation of Pde10a.

    Science.gov (United States)

    Hufgard, Jillian R; Williams, Michael T; Skelton, Matthew R; Grubisha, Olivera; Ferreira, Filipa M; Sanger, Helen; Wright, Mary E; Reed-Kessler, Tracy M; Rasmussen, Kurt; Duman, Ronald S; Vorhees, Charles V

    2017-06-01

    Major depressive disorder is a leading cause of suicide and disability. Despite this, current antidepressants provide insufficient efficacy in more than 60% of patients. Most current antidepressants are presynaptic reuptake inhibitors; postsynaptic signal regulation has not received as much attention as potential treatment targets. We examined the effects of disruption of the postsynaptic cyclic nucleotide hydrolyzing enzyme, phosphodiesterase (PDE) 1b, on depressive-like behavior and the effects on PDE1B protein in wild-type (WT) mice following stress. Littermate knockout (KO) and WT mice were tested in locomotor activity, tail suspension (TST), and forced swim tests (FST). FST was also used to compare the effects of two antidepressants, fluoxetine and bupropion, in KO versus WT mice. Messenger RNA (mRNA) expression changes were also determined. WT mice underwent acute or chronic stress and markers of stress and PDE1B expression were examined. Pde1b KO mice exhibited decreased TST and FST immobility. When treated with antidepressants, both WT and KO mice showed decreased FST immobility and the effect was additive in KO mice. Mice lacking Pde1b had increased striatal Pde10a mRNA expression. In WT mice, acute and chronic stress upregulated PDE1B expression while PDE10A expression was downregulated after chronic but not acute stress. PDE1B is a potential therapeutic target for depression treatment because of the antidepressant-like phenotype seen in Pde1b KO mice.

  6. IceBridge NSERC L1B Geolocated Meteorologic and Surface Temperature Data

    Data.gov (United States)

    National Aeronautics and Space Administration — The IceBridge National Suborbital Education & Research Center (NSERC) L1B Geolocated Meteorologic and Surface Temperature (IAMET1B) data set is a collection of...

  7. IceBridge NSERC L1B Geolocated Meteorologic and Surface Temperature Data, Version 1

    Data.gov (United States)

    National Aeronautics and Space Administration — The IceBridge National Suborbital Education & Research Center (NSERC) L1B Geolocated Meteorologic and Surface Temperature (IAMET1B) data set is a collection of...

  8. IceBridge LVIS POS/AV L1B Corrected Position and Attitude Data

    Data.gov (United States)

    National Aeronautics and Space Administration — The IceBridge LVIS POS/AV L1B Corrected Position and Attitude Data (IPPLV1B) data set contains georeferencing data from the Applanix 510 and 610 POS AV systems flown...

  9. IceBridge POS/AV L1B Corrected Position and Attitude Data

    Data.gov (United States)

    National Aeronautics and Space Administration — The IceBridge POS/AV L1B Corrected Position and Attitude (IPAPP1B) data set contains georeferencing data from the Applanix 510 POS AV system flown with the Digital...

  10. SMAP L1B Radiometer Half-Orbit Time-Ordered Brightness Temperatures V003

    Data.gov (United States)

    National Aeronautics and Space Administration — This Level-1B (L1B) product provides calibrated estimates of time-ordered geolocated brightness temperatures measured by the Soil Moisture Active Passive (SMAP)...

  11. Data of evolutionary structure change: 1B04B-3BAAA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B04B-3BAAA 1B04 3BAA B A MDRQQAERRAAELRELLNRYGYEYYVLDRPSVPDAEYDR...NLKTIRSLPLRLKEPVSLEARGEAFMPKASFLRLNEERKAR--ELFANPRNAAAGSLRQLDPKVAASRQLDLFVYGLADAEALGIASHSEALDYLQALGFKVNPERRR...DGLAISLRYENGVFVRGATRGDGTVGENITENLRTVRSVPMRLTEPISVEVRGECYMPKQSFVALNEEREENGQDIFANPRNAAAGSLRQLDTKIVAKRNLNTFLYTV... 353 TYR CA 427 3BAA A 3BAAA...hain>A 3BAAA EREENGQDIFAN

  12. IceBridge Riegl Laser Altimeter L1B Time-Tagged Laser Ranges

    Data.gov (United States)

    National Aeronautics and Space Administration — The NASA IceBridge Riegl Laser Altimeter L1B Time-Tagged Laser Ranges (ILUTP1B) data set contains laser ranges, returned pulses, and deviation for returned pulses in...

  13. Deletion of Protein Tyrosine Phosphatase 1B (PTP1B Enhances Endothelial Cyclooxygenase 2 Expression and Protects Mice from Type 1 Diabetes-Induced Endothelial Dysfunction.

    Directory of Open Access Journals (Sweden)

    David J Herren

    Full Text Available Protein tyrosine phosphatase 1B (PTP1B dephosphorylates receptors tyrosine kinase and acts as a molecular brake on insulin signaling pathway. Conditions of metabolic dysfunction increase PTP1B, when deletion of PTP1B protects against metabolic disorders by increasing insulin signaling. Although vascular insulin signaling contributes to the control of glucose disposal, little is known regarding the direct role of PTP1B in the control of endothelial function. We hypothesized that metabolic dysfunctions increase PTP1B expression in endothelial cells and that PTP1B deletion prevents endothelial dysfunction in situation of diminished insulin secretion. Type I diabetes (T1DM was induced in wild-type (WT and PTP1B-deficient mice (KO with streptozotocin (STZ injection. After 28 days of T1DM, KO mice exhibited a similar reduction in body weight and plasma insulin levels and a comparable increase in glycemia (WT: 384 ± 20 vs. Ko: 432 ± 29 mg/dL, cholesterol and triglycerides, as WT mice. T1DM increased PTP1B expression and impaired endothelial NO-dependent relaxation, in mouse aorta. PTP1B deletion did not affect baseline endothelial function, but preserved endothelium-dependent relaxation, in T1DM mice. NO synthase inhibition with L-NAME abolished endothelial relaxation in control and T1DM WT mice, whereas L-NAME and the cyclooxygenases inhibitor indomethacin were required to abolish endothelium relaxation in T1DM KO mice. PTP1B deletion increased COX-2 expression and PGI2 levels, in mouse aorta and plasma respectively, in T1DM mice. In parallel, simulation of diabetic conditions increased PTP1B expression and knockdown of PTP1B increased COX-2 but not COX-1 expression, in primary human aortic endothelial cells. Taken together these data indicate that deletion of PTP1B protected endothelial function by compensating the reduction in NO bioavailability by increasing COX-2-mediated release of the vasodilator prostanoid PGI2, in T1DM mice.

  14. 76 FR 62455 - Announcement of Updated Funding Availability for H-1B Technical Skills Training Grants

    Science.gov (United States)

    2011-10-07

    ... 10-13] Announcement of Updated Funding Availability for H-1B Technical Skills Training Grants AGENCY... the availability of $240 million for the H-1B Technical Skills Training Grants to be awarded through a... additional applicants to apply for the H-1B Technical Skills Training Grants competition that will close on...

  15. Data of evolutionary structure change: 2QU0A-2DN1B [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available >A 2QU0A WGKVGGNAGAYGence> HHHH...2QU0A-2DN1B 2QU0 2DN1 A B VLSAADKSNVKAAWGKVGGNAGAYGAEALERMFLSFPTT...index>0 2DN1 B 2DN1B ...ence>WGKVN--VDEVGence> GGG --HHHHH VAL CA 367 GLY CA 400 2QU0

  16. miR-200b mediates post-transcriptional repression of ZFHX1B

    DEFF Research Database (Denmark)

    Christoffersen, Nanna Rønbjerg; Silahtaroglu, Asli; Ørom, Ulf Lupo Andersson

    2007-01-01

    of E-cadherin. We show that Zfhx1b and miR-200b are regionally coexpressed in the adult mouse brain and that miR-200b represses the expression of Zfhx1b via multiple sequence elements present in the 3'-untranslated region. Overexpression of miR-200b leads to repression of endogenous ZFHX1B...

  17. Evaluation of visual impairment in Usher syndrome 1b and Usher syndrome 2a.

    NARCIS (Netherlands)

    Pennings, R.J.E.; Huygen, P.L.M.; Orten, D.J.; Wagenaar, M.; Aarem, A. van; Kremer, J.M.J.; Kimberling, W.J.; Cremers, C.W.R.J.; Deutman, A.F.

    2004-01-01

    PURPOSE: To evaluate visual impairment in Usher syndrome 1b (USH1b) and Usher syndrome 2a (USH2a). METHODS: We carried out a retrospective study of 19 USH1b patients and 40 USH2a patients. Cross-sectional regression analyses of the functional acuity score (FAS), functional field score (FFS) and

  18. Water molecule network and active site flexibility of apo protein tyrosine phosphatase 1B

    DEFF Research Database (Denmark)

    Pedersen, A.K.; Peters, Günther H.J.; Møller, K.B.

    2004-01-01

    Protein tyrosine phosphatase 1B (PTP1B) plays a key role as a negative regulator of insulin and leptin signalling and is therefore considered to be an important molecular target for the treatment of type 2 diabetes and obesity. Detailed structural information about the structure of PTP1B, including...

  19. HNF1B mutations associate with hypomagnesemia and renal magnesium wasting

    NARCIS (Netherlands)

    Adalat, Shazia; Woolf, Adrian S.; Johnstone, Karen A.; Wirsing, Andrea; Harries, Lorna W.; Long, David A.; Hennekam, Raoul C.; Ledermann, Sarah E.; Rees, Lesley; van't Hoff, William; Marks, Stephen D.; Trompeter, Richard S.; Tullus, Kjell; Winyard, Paul J.; Cansick, Janette; Mushtaq, Imran; Dhillon, Harjeeta K.; Bingham, Coralie; Edghill, Emma L.; Shroff, Rukshana; Stanescu, Horia; Ryffel, Gerhart U.; Ellard, Sian; Bockenhauer, Detlef

    2009-01-01

    Mutations in hepatocyte nuclear factor 1B (HNF1B), which is a transcription factor expressed in tissues including renal epithelia, associate with abnormal renal development. While studying renal phenotypes of children with HNF1B mutations, we identified a teenager who presented with tetany and

  20. Long-term impact of interferon beta-1b in patients with CIS

    DEFF Research Database (Denmark)

    Edan, G; Kappos, L; Montalbán, X

    2014-01-01

    OBJECTIVE: To examine the long-term impact of early treatment initiation of interferon beta-1b (IFNB1b, Betaferon/Betaseron) in patients with a first event suggestive of multiple sclerosis (MS). METHODS: In the original placebo-controlled phase of BENEFIT, patients were randomised to IFNB1b 250 μg...

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

    Science.gov (United States)

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

  2. Acute endocrine correlates of attack by lactating females in male mice: effects on plasma prolactin, luteinizing hormone and corticosterone levels.

    Science.gov (United States)

    Broida, J; Michael, S D; Svare, B

    1984-05-01

    Immediately following defeat inflicted by lactating Rockland-Swiss (R-S) albino mice, adult R-S male mice exhibited significant reductions in circulating prolactin (PRL) and luteinizing hormone (LH), but not corticosterone (CORT). These results suggest that acute neuroendocrine responses to intersex competition may be as dramatic as those previously reported for intermale encounters.

  3. Relationship of Prolactin Serum Levels and Breast Cancer with Hematological Factors Among Cases in Karbala Province, Iraq

    Directory of Open Access Journals (Sweden)

    Jaafar Kh. Ali

    2018-04-01

    Full Text Available Background: Globally, one million women are diagnosed with breast cancer and nearly half million die because of it. Breast cancer is one of the most common cancer which leads to mortality among women. Objectives: The main aim of this research is to find the relationship of prolactin level in women with breast cancer. Methods: The research was conducted in the Al-Hussein Medical City at Al-Hussein Center for the treatment of tumors and blood diseases. A total of 71 specimens were collected from females with breast cancer. Blood specimens were collected, and a blood group, PCV, Hb, ESR and prolactin level was evaluated. Results: The results show that most breast cancer cases were in age group 40-50 years, and less common among other age groups. The married women were 97% and the unmarried was 3% only. Most studied cases (43% were O +ve and 26% were A +ve blood group, in comparison to other blood groups. Also, many women show a slightly decrease in hemoglobin and PCV level (0.05. The prolactin levels were increased (31.5 ng/ml significantly in compare to normal range (2-27 ng/ml in women in all age groups. Conclusion: The study concludes that there was a relationship between prolactin level and breast cancer with a highly significant value.

  4. [In vitro evaluation of the gels properties prepared on Pluronic F-127 as vehicles for administration prolactin by injection].

    Science.gov (United States)

    Karolewicz, Bozena; Pawlik-Gałczyńska, Anna; Pluta, Janusz; Ryszka, Florian

    2011-01-01

    The aim of this study was to prepare a thermoresponsive formulations, which are a carrier for proteins--prolactin administered directly into solid tumor and which obtain sol-gel transitions at physiological ranges of temperature. Prolactin (PRL) is a hormone that in vivo and in vitro exhibits antiangiogenic properties. Application of this protein in the proposed formulations can be particularly advantageous because of its relatively low stability and limited ability to transmembrane penetration. The paper prepared thermoresponsive carriers, based on nonionic polymer Pluronic F-127 with selected excipients such as dextran 7000, PEG 400, Tween 20 and Tween 80. The sol-gel transition temperature of the formulations was investigated and their physicochemical properties such as pH, density, osmotic pressure were studied. In the remainder of the work carried out tests of prolactin release from the proposed media. The results obtained indicate that a significant influence on the theological parameters obtained carriers and the availability of pharmaceutical composition of prolactin was developed formulation.

  5. 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

  6. The HSV-1 mechanisms of cell-to-cell spread and fusion are critically dependent on host PTP1B.

    Directory of Open Access Journals (Sweden)

    Jillian C Carmichael

    2018-05-01

    Full Text Available All herpesviruses have mechanisms for passing through cell junctions, which exclude neutralizing antibodies and offer a clear path to neighboring, uninfected cells. In the case of herpes simplex virus type 1 (HSV-1, direct cell-to-cell transmission takes place between epithelial cells and sensory neurons, where latency is established. The spreading mechanism is poorly understood, but mutations in four different HSV-1 genes can dysregulate it, causing neighboring cells to fuse to produce syncytia. Because the host proteins involved are largely unknown (other than the virus entry receptor, we were intrigued by an earlier discovery that cells infected with wild-type HSV-1 will form syncytia when treated with salubrinal. A biotinylated derivative of this drug was used to pull down cellular complexes, which were analyzed by mass spectrometry. One candidate was a protein tyrosine phosphatase (PTP1B, and although it ultimately proved not to be the target of salubrinal, it was found to be critical for the mechanism of cell-to-cell spread. In particular, a highly specific inhibitor of PTP1B (CAS 765317-72-4 blocked salubrinal-induced fusion, and by itself resulted in a dramatic reduction in the ability of HSV-1 to spread in the presence of neutralizing antibodies. The importance of this phosphatase was confirmed in the absence of drugs by using PTP1B-/- cells. Importantly, replication assays showed that virus titers were unaffected when PTP1B was inhibited or absent. Only cell-to-cell spread was altered. We also examined the effects of salubrinal and the PTP1B inhibitor on the four Syn mutants of HSV-1, and strikingly different responses were found. That is, both drugs individually enhanced fusion for some mutants and reduced fusion for others. PTP1B is the first host factor identified to be specifically required for cell-to-cell spread, and it may be a therapeutic target for preventing HSV-1 reactivation disease.

  7. The HSV-1 mechanisms of cell-to-cell spread and fusion are critically dependent on host PTP1B.

    Science.gov (United States)

    Carmichael, Jillian C; Yokota, Hiroki; Craven, Rebecca C; Schmitt, Anthony; Wills, John W

    2018-05-01

    All herpesviruses have mechanisms for passing through cell junctions, which exclude neutralizing antibodies and offer a clear path to neighboring, uninfected cells. In the case of herpes simplex virus type 1 (HSV-1), direct cell-to-cell transmission takes place between epithelial cells and sensory neurons, where latency is established. The spreading mechanism is poorly understood, but mutations in four different HSV-1 genes can dysregulate it, causing neighboring cells to fuse to produce syncytia. Because the host proteins involved are largely unknown (other than the virus entry receptor), we were intrigued by an earlier discovery that cells infected with wild-type HSV-1 will form syncytia when treated with salubrinal. A biotinylated derivative of this drug was used to pull down cellular complexes, which were analyzed by mass spectrometry. One candidate was a protein tyrosine phosphatase (PTP1B), and although it ultimately proved not to be the target of salubrinal, it was found to be critical for the mechanism of cell-to-cell spread. In particular, a highly specific inhibitor of PTP1B (CAS 765317-72-4) blocked salubrinal-induced fusion, and by itself resulted in a dramatic reduction in the ability of HSV-1 to spread in the presence of neutralizing antibodies. The importance of this phosphatase was confirmed in the absence of drugs by using PTP1B-/- cells. Importantly, replication assays showed that virus titers were unaffected when PTP1B was inhibited or absent. Only cell-to-cell spread was altered. We also examined the effects of salubrinal and the PTP1B inhibitor on the four Syn mutants of HSV-1, and strikingly different responses were found. That is, both drugs individually enhanced fusion for some mutants and reduced fusion for others. PTP1B is the first host factor identified to be specifically required for cell-to-cell spread, and it may be a therapeutic target for preventing HSV-1 reactivation disease.

  8. Conformational analysis of GT1B ganglioside and its interaction with botulinum neurotoxin type B: a study by molecular modeling and molecular dynamics.

    Science.gov (United States)

    Venkateshwari, Sureshkumar; Veluraja, Kasinadar

    2012-01-01

    The conformational property of oligosaccharide GT1B in aqueous environment was studied by molecular dynamics (MD) simulation using all-atom model. Based on the trajectory analysis, three prominent conformational models were proposed for GT1B. Direct and water-mediated hydrogen bonding interactions stabilize these structures. The molecular modeling and 15 ns MD simulation of the Botulinum Neuro Toxin/B (BoNT/B) - GT1B complex revealed that BoNT/B can accommodate the GT1B in the single binding mode. Least mobility was seen for oligo-GT1B in the binding pocket. The bound conformation of GT1B obtained from the MD simulation of the BoNT/B-GT1B complex bear a close conformational similarity with the crystal structure of BoNT/A-GT1B complex. The mobility noticed for Arg 1268 in the dynamics was accounted for its favorable interaction with terminal NeuNAc. The internal NeuNAc1 tends to form 10 hydrogen bonds with BoNT/B, hence specifying this particular site as a crucial space for the therapeutic design that can restrict the pathogenic activity of BoNT/B.

  9. Prolactin Test

    Science.gov (United States)

    ... Macroprolactin Screening: Application of a New Strict Laboratory Definition of Macroprolactinemia. Clin ... by one of our partners, the American Society for Clinical Laboratory Science (ASCLS). Click on the ...

  10. Protein tyrosine phosphatase-1B (PTP1B) helps regulate EGF-induced stimulation of S-phase entry in human corneal endothelial cells

    Science.gov (United States)

    Ishino, Yutaka; Zhu, Cheng; Harris, Deshea L.

    2008-01-01

    Purpose Human corneal endothelial cells (HCEC), particularly from older donors, only proliferate weakly in response to EGF. The protein tyrosine phosphatase, PTP1B, is known to negatively regulate EGF-induced signaling in several cell types by dephosphorylating the epidermal growth factor receptor (EGFR). The current studies were conducted to determine whether PTP1B plays a role in regulating cell cycle entry in HCEC in response to EGF stimulation. Methods Donor corneas were obtained from the National Disease Research Interchange and accepted for study based on established exclusion criteria. PTP1B was localized in the endothelium of ex vivo corneas and in cultured cells by immunocytochemistry. Western blot analysis verified PTP1B protein expression in HCEC and then compared the relative expression of EGFR and PTP1B in HCEC from young (60 years old). The effect of inhibiting the activity of PTP1B on S-phase entry was tested by comparing time-dependent BrdU incorporation in subconfluent HCEC incubated in the presence or absence of the PTP1B inhibitor, CinnGEL 2Me, before EGF stimulation. Results PTP1B was localized in a punctate pattern mainly within the cytoplasm of HCEC in ex vivo corneas and cultured cells. Western blots revealed the presence of three PTP1B-positive bands in HCEC and the control. Further western blot analysis showed no significant age-related difference in expression of EGFR (p=0.444>0.05); however, PTP1B expression was significantly higher in HCEC from older donors (p=0.024<0.05). Pre-incubation of HCEC with the PTP1B inhibitor significantly increased (p=0.019<0.05) the number of BrdU positive cells by 48 h after EGF stimulation. Conclusions Both immunolocalization and western blot studies confirmed that PTP1B is expressed in HCEC. Staining patterns strongly suggest that at least a subset of PTP1B is localized to the cytoplasm and most likely to the endoplasmic reticulum, the known site of EGFR/PTP1B interaction following EGF stimulation. PTP1B

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

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    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

  12. Erupção acneiforme aguda induzida por interferon beta-1b durante tratamento para esclerose múltipla Acute acneiform eruption induced by interferon beta-1b during treatment for multiple sclerosis

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    Dário Júnior de Freitas Rosa

    2011-04-01

    Full Text Available Esclerose múltipla é uma doença inflamatória desmielinizante, com presumida origem autoimune, que afeta o sistema nervoso central. A principal modalidade terapêutica é baseada no uso de imunomoduladores, como o interferon beta, que são geralmente bem tolerados. As manifestações cutâneas secundárias ao interferon beta-1b são representadas, na maioria das vezes, por reações no local de sua aplicação subcutânea. Descrevemos o caso de uma paciente do sexo feminino que desenvolveu um quadro de erupção acneiforme pelo interferon beta-1b.Multiple sclerosis is an inflammatory demyelinating disease of presumed autoimmune origin that affects the central nervous system. The main form of therapy is based on the use of immunomodulators such as interferon beta, which are usually well tolerated. Skin manifestations resulting from treatment with interferon beta-1b consist principally of reactions at the site of subcutaneous application of the drug. The present case report describes a female patient who developed an acneiform eruption resulting from treatment with interferon beta-1b.

  13. CYP1B1 expression, a potential risk factor for breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Goth-Goldstein, Regine; Erdmann, Christine A.; Russell, Marion

    2001-05-31

    CYP1B1 expression in non-tumor breast tissue from breast cancer patients and cancer-free individuals was determined to test the hypothesis that high CYP1B1 expression is a risk factor for breast cancer. Large interindividual variations in CYP1B1 expression were found with CYP1B1 levels notably higher in breast cancer patients than cancer-free individuals. The results indicate that CYP1B1 might play a role in breast cancer either through increased PAH activation or through metabolism of endogenous estrogen to a carcinogenic derivative.

  14. Lmx1b-targeted cis-regulatory modules involved in limb dorsalization.

    Science.gov (United States)

    Haro, Endika; Watson, Billy A; Feenstra, Jennifer M; Tegeler, Luke; Pira, Charmaine U; Mohan, Subburaman; Oberg, Kerby C

    2017-06-01

    Lmx1b is a homeodomain transcription factor responsible for limb dorsalization. Despite striking double-ventral (loss-of-function) and double-dorsal (gain-of-function) limb phenotypes, no direct gene targets in the limb have been confirmed. To determine direct targets, we performed a chromatin immunoprecipitation against Lmx1b in mouse limbs at embryonic day 12.5 followed by next-generation sequencing (ChIP-seq). Nearly 84% ( n =617) of the Lmx1b-bound genomic intervals (LBIs) identified overlap with chromatin regulatory marks indicative of potential cis -regulatory modules (PCRMs). In addition, 73 LBIs mapped to CRMs that are known to be active during limb development. We compared Lmx1b-bound PCRMs with genes regulated by Lmx1b and found 292 PCRMs within 1 Mb of 254 Lmx1b-regulated genes. Gene ontological analysis suggests that Lmx1b targets extracellular matrix production, bone/joint formation, axonal guidance, vascular development, cell proliferation and cell movement. We validated the functional activity of a PCRM associated with joint-related Gdf5 that provides a mechanism for Lmx1b-mediated joint modification and a PCRM associated with Lmx1b that suggests a role in autoregulation. This is the first report to describe genome-wide Lmx1b binding during limb development, directly linking Lmx1b to targets that accomplish limb dorsalization. © 2017. Published by The Company of Biologists Ltd.

  15. Protein tyrosine phosphatase PTP1B is involved in hippocampal synapse formation and learning.

    Directory of Open Access Journals (Sweden)

    Federico Fuentes

    Full Text Available ER-bound PTP1B is expressed in hippocampal neurons, and accumulates among neurite contacts. PTP1B dephosphorylates ß-catenin in N-cadherin complexes ensuring cell-cell adhesion. Here we show that endogenous PTP1B, as well as expressed GFP-PTP1B, are present in dendritic spines of hippocampal neurons in culture. GFP-PTP1B overexpression does not affect filopodial density or length. In contrast, impairment of PTP1B function or genetic PTP1B-deficiency leads to increased filopodia-like dendritic spines and a reduction in mushroom-like spines, while spine density is unaffected. These morphological alterations are accompanied by a disorganization of pre- and post-synapses, as judged by decreased clustering of synapsin-1 and PSD-95, and suggest a dynamic synaptic phenotype. Notably, levels of ß-catenin-Tyr-654 phosphorylation increased ∼5-fold in the hippocampus of adult PTP1B(-/- (KO mice compared to wild type (WT mice and this was accompanied by a reduction in the amount of ß-catenin associated with N-cadherin. To determine whether PTP1B-deficiency alters learning and memory, we generated mice lacking PTP1B in the hippocampus and cortex (PTP1B(fl/fl-Emx1-Cre. PTP1B(fl/fl-Emx1-Cre mice displayed improved performance in the Barnes maze (decreased time to find and enter target hole, utilized a more efficient strategy (cued, and had better recall compared to WT controls. Our results implicate PTP1B in structural plasticity within the hippocampus, likely through modulation of N-cadherin function by ensuring dephosphorylation of ß-catenin on Tyr-654. Disruption of hippocampal PTP1B function or expression leads to elongation of dendritic filopodia and improved learning and memory, demonstrating an exciting novel role for this phosphatase.

  16. PTP1B confers liver fibrosis by regulating the activation of hepatic stellate cells

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Pei-Jie; Cai, Shuang-Peng; Yang, Yang; Li, Wan-Xia; Huang, Cheng; Meng, Xiao-Ming; Li, Jun, E-mail: lj@ahmu.edu.cn

    2016-02-01

    Liver fibrosis is a reversible wound-healing response to chronic hepatic injuries. Activation of hepatic stellate cells (HSCs) plays a pivotal role in the development of hepatic fibrosis. The currently accepted mechanism for the resolution of liver fibrosis is the apoptosis and inactivation of activated HSCs. Protein tyrosine phosphatase 1B (PTP1B), a prototype of non-receptor protein tyrosine phosphatase, is proved to be a vital modulator in cardiac fibrogenesis. However, the precise role of PTP1B on liver fibrosis and HSC activation is still unclear. Our study showed that the expression of PTP1B was elevated in fibrotic liver but reduced after spontaneous recovery. Moreover, stimulation of HSC-T6 cells with transforming growth factor-β1 (TGF-β1) resulted in a dose/time-dependent increase of PTP1B mRNA and protein. Co-incubation of HSC-T6 cells with PTP1B-siRNA inhibited the cell proliferation and activation induced by TGF-β1. Additionally, both mRNA and protein of PTP1B were dramatically decreased in inactivated HSCs after treated with adipogenic differentiation mixture (MDI). Over-expression of PTP1B hindered the inactivation of HSC-T6 cells induced by MDI. These observations revealed a regulatory role of PTP1B in liver fibrosis and implied PTP1B as a potential therapeutic target. - Highlights: • The expression of PTP1B in the fibrotic livers and recovery livers • The expression of PTP1B in activated and inactivated HSCs • Blockade of PTP1B inhibited the TGF-β1-induced proliferation and activation of HSCs. • Over-expression of PTP1B abolished the inactivation of HSCs induced by MDI.

  17. PTP1B confers liver fibrosis by regulating the activation of hepatic stellate cells

    International Nuclear Information System (INIS)

    Chen, Pei-Jie; Cai, Shuang-Peng; Yang, Yang; Li, Wan-Xia; Huang, Cheng; Meng, Xiao-Ming; Li, Jun

    2016-01-01

    Liver fibrosis is a reversible wound-healing response to chronic hepatic injuries. Activation of hepatic stellate cells (HSCs) plays a pivotal role in the development of hepatic fibrosis. The currently accepted mechanism for the resolution of liver fibrosis is the apoptosis and inactivation of activated HSCs. Protein tyrosine phosphatase 1B (PTP1B), a prototype of non-receptor protein tyrosine phosphatase, is proved to be a vital modulator in cardiac fibrogenesis. However, the precise role of PTP1B on liver fibrosis and HSC activation is still unclear. Our study showed that the expression of PTP1B was elevated in fibrotic liver but reduced after spontaneous recovery. Moreover, stimulation of HSC-T6 cells with transforming growth factor-β1 (TGF-β1) resulted in a dose/time-dependent increase of PTP1B mRNA and protein. Co-incubation of HSC-T6 cells with PTP1B-siRNA inhibited the cell proliferation and activation induced by TGF-β1. Additionally, both mRNA and protein of PTP1B were dramatically decreased in inactivated HSCs after treated with adipogenic differentiation mixture (MDI). Over-expression of PTP1B hindered the inactivation of HSC-T6 cells induced by MDI. These observations revealed a regulatory role of PTP1B in liver fibrosis and implied PTP1B as a potential therapeutic target. - Highlights: • The expression of PTP1B in the fibrotic livers and recovery livers • The expression of PTP1B in activated and inactivated HSCs • Blockade of PTP1B inhibited the TGF-β1-induced proliferation and activation of HSCs. • Over-expression of PTP1B abolished the inactivation of HSCs induced by MDI.

  18. Essential Roles for ARID1B in Dendritic Arborization and Spine Morphology of Developing Pyramidal Neurons

    Science.gov (United States)

    Ka, Minhan; Chopra, Divyan A.; Dravid, Shashank M.

    2016-01-01

    De novo truncating mutations in ARID1B, a chromatin-remodeling gene, cause Coffin–Siris syndrome, a developmental disorder characterized by intellectual disability and speech impairment; however, how the genetic elimination leads to cognitive dysfunction remains unknown. Thus, we investigated the neural functions of ARID1B during brain development. Here, we show that ARID1B regulates dendritic differentiation in the developing mouse brain. We knocked down ARID1B expression in mouse pyramidal neurons using in utero gene delivery methodologies. ARID1B knockdown suppressed dendritic arborization of cortical and hippocampal pyramidal neurons in mice. The abnormal development of dendrites accompanied a decrease in dendritic outgrowth into layer I. Furthermore, knockdown of ARID1B resulted in aberrant dendritic spines and synaptic transmission. Finally, ARID1B deficiency led to altered expression of c-Fos and Arc, and overexpression of these factors rescued abnormal differentiation induced by ARID1B knockdown. Our results demonstrate a novel role for ARID1B in neuronal differentiation and provide new insights into the origin of cognitive dysfunction associated with developmental intellectual disability. SIGNIFICANCE STATEMENT Haploinsufficiency of ARID1B, a component of chromatin remodeling complex, causes intellectual disability. However, the role of ARID1B in brain development is unknown. Here, we demonstrate that ARID1B is required for neuronal differentiation in the developing brain, such as in dendritic arborization and synapse formation. Our findings suggest that ARID1B plays a critical role in the establishment of cognitive circuitry by regulating dendritic complexity. Thus, ARID1B deficiency may cause intellectual disability via abnormal brain wiring induced by the defective differentiation of cortical neurons. PMID:26937011

  19. Lipoic Acid Decreases the Viability of Breast Cancer Cells and Activity of PTP1B and SHP2.

    Science.gov (United States)

    Kuban-Jankowska, Alicja; Gorska-Ponikowska, Magdalena; Wozniak, Michal

    2017-06-01

    Protein tyrosine phosphatases PTP1B and SHP2 are potential targets for anticancer therapy, because of the essential role they play in the development of tumors. PTP1B and SHP2 are overexpressed in breast cancer cells, thus inhibition of their activity can be potentially effective in breast cancer therapy. Lipoic acid has been previously reported to inhibit the proliferation of colon, breast and thyroid cancer cells. We investigated the effect of alpha-lipoic acid (ALA) and its reduced form of dihydrolipoic acid (DHLA) on the viability of MCF-7 cancer cells and on the enzymatic activity of PTP1B and SHP2 phosphatases. ALA and DHLA decrease the activity of PTP1B and SHP2, and have inhibitory effects on the viability and proliferation of breast cancer cells. ALA and DHLA can be considered as potential agents for the adjunctive treatment of breast cancer. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  20. Study on the serum prolactin (PRL) level in post-menopausal women

    International Nuclear Information System (INIS)

    Li Wenqi; Li Xin; Zhou Jiwen; Zhou Zhengli

    2004-01-01

    Objective: To explore the clinical value of determination of serum PRL levels inpost-menopausal women. Methods: Serum PRL levels were determined with RIA in 596 post-menopausal women (age 45-59, mean 55). Results: The normal range of serum PRL level in this laboratory was 0-30 ng/ml. Among the 596 women tested, 77(13%) had their PRL levels above 30 ng/ml. Further investigation with CT and/or MRI revealed presence of micro-pituitary-adenoma in 31 of the Symptoms of menopausal syndrome and osteoporosis were much more severe in women with hyperprolactinemia then in those without. Conclusion: As hyperprolactinemia might be a high risk factor for development of breast cancer, hormone replacement therapy (HRT) in menopausal women with hyperprolactinemia should be applied very cautiously, even withheld at all. Determination of serum prolactin levels in post-menopausal women is of practical clinical value. (authors)

  1. Small scale extraction and purification of human prolactin for the preparation of radioimmunoassay reagents

    International Nuclear Information System (INIS)

    Dias, L.E.M.F.

    1989-01-01

    Purification of human prolactin from pituitaries was carried out in our laboratory to obtain a pure reagent for use in RIA. The extraction and purification procedure was adapted from the method of Mc. Lean et al., and it involves the following steps: 1. Extraction of frozen pituitaries in buffers 0.14M phosphate/citrate pH 4.0 and 0.05M ammonium acetate pH 10.0. 2. Purification by hydrophobic interaction chromatography on Phenyl-Sepharose CL-4B in the presence of acetonitrile. 3. Purification by anion exchange chromatography on DEAE-Sepharose Cl-68. The purification method is considered effective for obtaining a hPrl of the purity needed for radioassay purposes, having the advantage of rapidity and relative simplicity. (author) [pt

  2. Depletion of pituitary prolactin by cysteamine is due to loss of immunological activity

    Energy Technology Data Exchange (ETDEWEB)

    Scammell, J.G.; Dannies, P.S.

    1984-03-01

    The mechanism by which cysteamine reduces the prolactin(PRL) content of pituitary cells was studied in primary cultures of estradiol-induced pituitary tumors in Fischer 344 rats. The PRL content of these cells was effectively decreased by cysteamine, with an IC50 of 0.2 mM. Cells previously labeled with (/sup 3/H)leucine were exposed to cysteamine (0.25 mM), and the intracellular content of (/sup 3/H)PRL was measured by immunological or nonimmunological means, that is by immunoprecipitation and electrophoresis or by electrophoresis alone. The intracellular concentration of immunoreactive (/sup 3/H)PRL was reduced by 53% by cysteamine, whereas (/sup 3/H)PRL quantified by electrophoresis alone was not significantly affected. Our data indicate that cysteamine reduces the PRL content of pituitary tumor cells by causing the loss of its immunoreactivity.

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

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    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.

  4. Depletion of pituitary prolactin by cysteamine is due to loss of immunological activity

    International Nuclear Information System (INIS)

    Scammell, J.G.; Dannies, P.S.

    1984-01-01

    The mechanism by which cysteamine reduces the prolactin(PRL) content of pituitary cells was studied in primary cultures of estradiol-induced pituitary tumors in Fischer 344 rats. The PRL content of these cells was effectively decreased by cysteamine, with an IC50 of 0.2 mM. Cells previously labeled with [ 3 H]leucine were exposed to cysteamine (0.25 mM), and the intracellular content of [ 3 H]PRL was measured by immunological or nonimmunological means, that is by immunoprecipitation and electrophoresis or by electrophoresis alone. The intracellular concentration of immunoreactive [ 3 H]PRL was reduced by 53% by cysteamine, whereas [ 3 H]PRL quantified by electrophoresis alone was not significantly affected. Our data indicate that cysteamine reduces the PRL content of pituitary tumor cells by causing the loss of its immunoreactivity

  5. Correlation and comparison of Nb2 lymphoma cell bioassay with radioimmunoassay for human prolactin

    International Nuclear Information System (INIS)

    Subramanian, M.G.; Spirtos, N.J.; Moghissi, K.S.; Magyar, D.M.; Hayes, M.F.; Gala, R.R.

    1984-01-01

    Serum samples from groups of men and women with normal and elevated prolactin (PRL) levels were assayed by radioimmunoassay (RIA) and by Nb 2 lymphoma cell bioassay (BA) for the presence of PRL. Because the Nb 2 lymphoma cells respond to both PRL and growth hormone, BA for PRL activity was carried out before and after neutralization of growth hormone in the serum samples. There were excellent correlations between RIA and BA both in euprolactinemic and hyperprolactinemic subjects. On an absolute basis, RIA and BA values were similar in the euprolactinemic group (6.6 +/- 0.8 versus 6.2 +/- 1.0), whereas in the hyperprolactinemic group, RIA values were significantly higher than the BA results. The two assay systems also appeared to correlate better in women who were hyperprolactinemic, with obvious menstrual cycle disturbances, than in hyperprolactinemic women without menstrual cycle disturbances

  6. Response of the pigeon crop sac to mammotrophic hormones: Comparison between relaxin and prolactin

    International Nuclear Information System (INIS)

    Bani, G.; Sacchi, T.B.; Bigazzi, M.

    1990-01-01

    The effects of relaxin (RLX), a hormone that has previously been demonstrated to have mammotrophic properties, were studied in the pigeon crop sac, a well-known target organ for mammotrophic and lactogenic hormones, and compared with the effects produced by prolactin (PRL). The two hormones were injected directly over the crop at different doses and the response was evaluated after differing times of exposure. RLX causes a dose-related increase in wet and dry weights and [ 3 H]thymidine and [ 3 H]uridine uptake by the crop mucosa, as well as morphological changes indicating growth and differentiation of the epithelial cells similar to those occurring during physiological activation in incubation and hatching. At the doses assayed, the effects of RLX were nearly identical to those obtained following PRL in the short-term experiments, but differences in functional responses were found in the long-term experiment

  7. Prolactin Alters the Mammary Epithelial Hierarchy, Increasing Progenitors and Facilitating Ovarian Steroid Action

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    Kathleen A. O'Leary

    2017-10-01

    Full Text Available Hormones drive mammary development and function and play critical roles in breast cancer. Epidemiologic studies link prolactin (PRL to increased risk for aggressive cancers that express estrogen receptor α (ERα. However, in contrast to ovarian steroids, PRL actions on the mammary gland outside of pregnancy are poorly understood. We employed the transgenic NRL-PRL model to examine the effects of PRL alone and with defined estrogen/progesterone exposure on stem/progenitor activity and regulatory networks that drive epithelial differentiation. PRL increased progenitors and modulated transcriptional programs, even without ovarian steroids, and with steroids further raised stem cell activity associated with elevated canonical Wnt signaling. However, despite facilitating some steroid actions, PRL opposed steroid-driven luminal maturation and increased CD61+ luminal cells. Our findings demonstrate that PRL can powerfully influence the epithelial hierarchy alone and temper the actions of ovarian steroids, which may underlie its role in the development of breast cancer.

  8. Plasma prolactin and homovanillic acid as markers for psychopathology and abnormal movements after neuroleptic dose decrease.

    Science.gov (United States)

    Newcomer, J W; Riney, S J; Vinogradov, S; Csernansky, J G

    1992-01-01

    Plasma prolactin concentration (pPRL), plasma homovanillic acid concentration (pHVA), and symptomatology were measured in 24 male subjects with schizophrenia during maintenance haloperidol treatment. Fourteen subjects subsequently underwent 50 percent dose decreases under placebo-controlled, double-blind conditions. At baseline, a significant inverse correlation was found between pPRL and both tardive dyskinesia (TD) and "thinking disorder"; pPRL was directly correlated with negative symptoms. No such relationship was found with pHVA. In the patients who underwent a dose decrease, no relationship was found between baseline pPRL or pHVA and any clinical variable after the decrease. These data do not support the use of baseline pPRL or pHVA as markers of central dopamine function subsequent to a neuroleptic dose decrease.

  9. Teaching Form as Form

    DEFF Research Database (Denmark)

    Keiding, Tina Bering

    2012-01-01

    understanding of form per se, or, to use an expression from this text, of form as form. This challenge can be reduced to one question: how can design teaching support students in achieving not only the ability to recognize and describe different form-related concepts in existing design (i.e. analytical...

  10. Genital Sensory Stimulation Shifts Estradiol Intraoviductal Signaling from Nongenomic to Genomic Pathways, Independently from Prolactin Surges

    Directory of Open Access Journals (Sweden)

    C PEÑARROJA-MATUTAN0

    2007-01-01

    Full Text Available Estradiol (E2 accelerates oviductal egg transport through nongenomic pathways involving oviductal protein phosphorylation in non-mated rats, and through genomic pathways in mated rats. Here we investigated the ability of cervico-vaginal stimulation (CVS to switch the mode of action of E2 in the absence of other male-associated components. Pro-estrous rats were subjected to CVS with a glass rod and 12 hours later were injected subcutaneously with E2 and intrabursally with the RNA synthesis inhibitor Actinomycin D or the protein phosphorylation inhibitor H-89. The number of eggs in the oviduct, assessed 24 h later, showed that Actinomycin D, but not H-89 blocked the E2-induced egg transport acceleration. This clearly indicates that CVS alone, without other mating-associated signals, is able to shift E2 signaling from nongenomic to genomic pathways. Since mating and CVS activate a neuroendocrine reflex that causes iterative prolactin (PRL surges, the involvement of PRL pathway in this phenomenon was evaluated. Prolactin receptor mRNA and protein expression in the rat oviduct was demonstrated by RT-PCR and Western blot, but their levels were not different on day 2 of the cycle (C2 or pregnancy (P2. Activated ST AT 5a/b (phosphorylated was detected by Western blot on P2 in the ovary, but not in the oviduct, showing that mating does not stimulate this PRL signalling pathway in the oviduct. Other rats subjected to CVS in the evening of pro-estrus were treated with bromoergocriptine to suppress PRL surges. In these rats, H-89 did not block the E2-induced acceleration of egg transport suggesting that PRL surges are not essential to shift E2 signaling pathways in the oviduct. We conclude that CVS is one of the components of mating that shifts E2 signaling in the oviduct from nongenomic to genomic pathways, and this effect is independent of PRL surges elicited by mating

  11. Suppression of prolactin gene expression in GH cells correlates with site-specific DNA methylation.

    Science.gov (United States)

    Zhang, Z X; Kumar, V; Rivera, R T; Pasion, S G; Chisholm, J; Biswas, D K

    1989-10-01

    Prolactin- (PRL) producing and nonproducing subclones of the GH line of (rat) pituitary tumor cells have been compared to elucidate the regulatory mechanisms of PRL gene expression. Particular emphasis was placed on delineating the molecular basis of the suppressed state of the PRL gene in the prolactin-nonproducing (PRL-) GH subclone (GH(1)2C1). We examined six methylatable cytosine residues (5, -CCGG- and 1, -GCGC-) within the 30-kb region of the PRL gene in these subclones. This analysis revealed that -CCGG-sequences of the transcribed region, and specifically, one in the fourth exon of the PRL gene, were heavily methylated in the PRL-, GH(1)2C1 cells. Furthermore, the inhibition of PRL gene expression in GH(1)2C1 was reversed by short-term treatment of the cells with a sublethal concentration of azacytidine (AzaC), an inhibitor of DNA methylation. The reversion of PRL gene expression by AzaC was correlated with the concurrent demethylation of the same -CCGG- sequences in the transcribed region of PRL gene. An inverse correlation between PRL gene expression and the level of methylation of the internal -C- residues in the specific -CCGG-sequence of the transcribed region of the PRL gene was demonstrated. The DNase I sensitivity of these regions of the PRL gene in PRL+, PRL-, and AzaC-treated cells was also consistent with an inverse relationship between methylation state, a higher order of structural modification, and gene expression.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Progesterone receptors (PR) mediate STAT actions: PR and prolactin receptor signaling crosstalk in breast cancer models.

    Science.gov (United States)

    Leehy, Katherine A; Truong, Thu H; Mauro, Laura J; Lange, Carol A

    2018-02-01

    Estrogen is the major mitogenic stimulus of mammary gland development during puberty wherein ER signaling acts to induce abundant PR expression. PR signaling, in contrast, is the primary driver of mammary epithelial cell proliferation in adulthood. The high circulating levels of progesterone during pregnancy signal through PR, inducing expression of the prolactin receptor (PRLR). Cooperation between PR and prolactin (PRL) signaling, via regulation of downstream components in the PRL signaling pathway including JAKs and STATs, facilitates the alveolar morphogenesis observed during pregnancy. Indeed, these pathways are fully integrated via activation of shared signaling pathways (i.e. JAKs, MAPKs) as well as by the convergence of PRs and STATs at target genes relevant to both mammary gland biology and breast cancer progression (i.e. proliferation, stem cell outgrowth, tissue cell type heterogeneity). Thus, rather than a single mediator such as ER, transcription factor cascades (ER>PR>STATs) are responsible for rapid proliferative and developmental programming in the normal mammary gland. It is not surprising that these same mediators typify uncontrolled proliferation in a majority of breast cancers, where ER and PR are most often co-expressed and may cooperate to drive malignant tumor progression. This review will primarily focus on the integration of PR and PRL signaling in breast cancer models and the importance of this cross-talk in cancer progression in the context of mammographic density. Components of these PR/PRL signaling pathways could offer alternative drug targets and logical complements to anti-ER or anti-estrogen-based endocrine therapies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Functions of two distinct prolactin-releasing peptides evolved from a common ancestral gene

    Directory of Open Access Journals (Sweden)

    Tetsuya eTachibana

    2014-11-01

    Full Text Available Prolactin-releasing peptide (PrRP is one of the RF-amide peptides and was originally identified in the bovine hypothalamus as a stimulator of prolactin (PRL release. Independently, another RF-amide peptide was found in Japanese crucian carp and named Carassius RFa (C-RFa, which shows high homology to PrRP and stimulates PRL secretion in teleost fish. Therefore, C-RFa has been recognized as fish PrRP. However, recent work has revealed that PrRP and C-RFa in non-mammalian vertebrates are encoded by separate genes originated through duplication of an ancestral gene. Indeed, both PrRP and C-RFa are suggested to exist in teleost, amphibian, reptile, and avian species. Therefore, we propose that non-mammalian PrRP (C-RFa be renamed PrRP2. Despite a common evolutionary origin, PrRP2 appears to be a physiological regulator of PRL, whereas this is not a consistent role for PrRP itself. Further work revealed that the biological functions of PrRP and PrRP2 are not limited solely to PRL release, because they are also neuromodulators of several hypothalamus-pituitary axes and are involved in some brain circuits related to the regulation of food intake, stress, and cardiovascular functions. However, these actions appear to be different among vertebrates. For example, central injection of PrRP inhibits feeding behavior in rodents and teleosts while it stimulates it in chicks. Therefore, both PrRP and PrRP2 have acquired diverse actions through evolution. In this review, we integrate the burgeoning information of structures, expression profiles, and multiple biological actions of PrRP in higher vertebrates, as well as those of PrRP2 in non-mammals.

  14. Regulation of gill claudin paralogs by salinity, cortisol and prolactin in Mozambique tilapia (Oreochromis mossambicus).

    Science.gov (United States)

    Tipsmark, Christian K; Breves, Jason P; Rabeneck, D Brett; Trubitt, Rebecca T; Lerner, Darren T; Grau, E Gordon

    2016-09-01

    In euryhaline teleosts, reorganization of gill tight junctions during salinity acclimation involves dynamic expression of specific claudin (Cldn) paralogs. We identified four transcripts encoding Cldn tight junction proteins in the tilapia gill transcriptome: cldn10c, cldn10e, cldn28a and cldn30. A tissue distribution experiment found cldn10c and cldn10e expression levels in the gill to be 100-fold higher than any other tissues examined. cldn28a and cldn30 levels in the gill were 10-fold greater than levels in other tissues. Expression of these genes in Mozambique tilapia was examined during acclimation to fresh water (FW), seawater (SW), and in response to hormone treatments. Transfer of tilapia from FW to SW elevated cldn10c and cldn10e, while cldn28a and cldn30 were stimulated following transfer from SW to FW. In hypophysectomized tilapia transferred to FW, pituitary extirpation induced reduced expression of cldn10c, cldn10e and cldn28a; these effects were mitigated equally by either prolactin or cortisol replacement. In vitro experiments with gill filaments showed that cortisol stimulated expression of all four cldns examined, suggesting a direct action of cortisol in situ. Our data indicate that elevated cldn10c and cldn10e expression is important during acclimation of tilapia to SW possibly by conferring ion specific paracellular permeability. On the other hand, expression of cldn28a and cldn30 appears to contribute to reorganization of branchial epithelium during FW acclimation. Hormone treatment experiments showed that particular FW- and SW-induced cldns are controlled by cortisol and prolactin. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. 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...

  16. Expanding the phenotypic spectrum of ARID1B-mediated disorders and identification of altered cell-cycle dynamics due to ARID1B haploinsufficiency

    DEFF Research Database (Denmark)

    Sim, J. C. H.; White, S. M.; Fitzpatrick, E.

    2014-01-01

    Background: Mutations in genes encoding components of the Brahma-associated factor (BAF) chromatin remodeling complex have recently been shown to contribute to multiple syndromes characterised by developmental delay and intellectual disability. ARID1B mutations have been identified as the predomi......Background: Mutations in genes encoding components of the Brahma-associated factor (BAF) chromatin remodeling complex have recently been shown to contribute to multiple syndromes characterised by developmental delay and intellectual disability. ARID1B mutations have been identified...

  17. Expanding the phenotypic spectrum of ARID1B-mediated disorders and identification of altered cell-cycle dynamics due to ARID1B haploinsufficiency.

    Science.gov (United States)

    Sim, Joe C H; White, Susan M; Fitzpatrick, Elizabeth; Wilson, Gabrielle R; Gillies, Greta; Pope, Kate; Mountford, Hayley S; Torring, Pernille M; McKee, Shane; Vulto-van Silfhout, Anneke T; Jhangiani, Shalini N; Muzny, Donna M; Leventer, Richard J; Delatycki, Martin B; Amor, David J; Lockhart, Paul J

    2014-03-27

    Mutations in genes encoding components of the Brahma-associated factor (BAF) chromatin remodeling complex have recently been shown to contribute to multiple syndromes characterised by developmental delay and intellectual disability. ARID1B mutations have been identified as the predominant cause of Coffin-Siris syndrome and have also been shown to be a frequent cause of nonsyndromic intellectual disability. Here, we investigate the molecular basis of a patient with an overlapping but distinctive phenotype of intellectual disability, plantar fat pads and facial dysmorphism. High density microarray analysis of the patient demonstrated a heterozygous deletion at 6q25.3, which resulted in the loss of four genes including AT Rich Interactive Domain 1B (ARID1B). Subsequent quantitative real-time PCR analysis revealed ARID1B haploinsufficiency in the patient. Analysis of both patient-derived and ARID1B knockdown fibroblasts after serum starvation demonstrated delayed cell cycle re-entry associated with reduced cell number in the S1 phase. Based on the patient's distinctive phenotype, we ascertained four additional patients and identified heterozygous de novo ARID1B frameshift or nonsense mutations in all of them. This study broadens the spectrum of ARID1B associated phenotypes by describing a distinctive phenotype including plantar fat pads but lacking the hypertrichosis or fifth nail hypoplasia associated with Coffin-Siris syndrome. We present the first direct evidence in patient-derived cells that alterations in cell cycle contribute to the underlying pathogenesis of syndromes associated with ARID1B haploinsufficiency.

  18. The Nonreceptor Protein Tyrosine Phosphatase PTP1B Binds to the Cytoplasmic Domain of N-Cadherin and Regulates the Cadherin–Actin Linkage

    Science.gov (United States)

    Balsamo, Janne; Arregui, Carlos; Leung, TinChung; Lilien, Jack

    1998-01-01

    Cadherin-mediated adhesion depends on the association of its cytoplasmic domain with the actin-containing cytoskeleton. This interaction is mediated by a group of cytoplasmic proteins: α-and β- or γ- catenin. Phosphorylation of β-catenin on tyrosine residues plays a role in controlling this association and, therefore, cadherin function. Previous work from our laboratory suggested that a nonreceptor protein tyrosine phosphatase, bound to the cytoplasmic domain of N-cadherin, is responsible for removing tyrosine-bound phosphate residues from β-catenin, thus maintaining the cadherin–actin connection (Balsamo et al., 1996). Here we report the molecular cloning of the cadherin-associated tyrosine phosphatase and identify it as PTP1B. To definitively establish a causal relationship between the function of cadherin-bound PTP1B and cadherin-mediated adhesion, we tested the effect of expressing a catalytically inactive form of PTP1B in L cells constitutively expressing N-cadherin. We find that expression of the catalytically inactive PTP1B results in reduced cadherin-mediated adhesion. Furthermore, cadherin is uncoupled from its association with actin, and β-catenin shows increased phosphorylation on tyrosine residues when compared with parental cells or cells transfected with the wild-type PTP1B. Both the transfected wild-type and the mutant PTP1B are found associated with N-cadherin, and recombinant mutant PTP1B binds to N-cadherin in vitro, indicating that the catalytically inactive form acts as a dominant negative, displacing endogenous PTP1B, and rendering cadherin nonfunctional. Our results demonstrate a role for PTP1B in regulating cadherin-mediated cell adhesion. PMID:9786960

  19. Reduced expression of APC-1B but not APC-1A by the deletion of promoter 1B is responsible for familial adenomatous polyposis.

    Science.gov (United States)

    Yamaguchi, Kiyoshi; Nagayama, Satoshi; Shimizu, Eigo; Komura, Mitsuhiro; Yamaguchi, Rui; Shibuya, Tetsuo; Arai, Masami; Hatakeyama, Seira; Ikenoue, Tsuneo; Ueno, Masashi; Miyano, Satoru; Imoto, Seiya; Furukawa, Yoichi

    2016-05-24

    Germline mutations in the tumor suppressor gene APC are associated with familial adenomatous polyposis (FAP). Here we applied whole-genome sequencing (WGS) to the DNA of a sporadic FAP patient in which we did not find any pathological APC mutations by direct sequencing. WGS identified a promoter deletion of approximately 10 kb encompassing promoter 1B and exon1B of APC. Additional allele-specific expression analysis by deep cDNA sequencing revealed that the deletion reduced the expression of the mutated APC allele to as low as 11.2% in the total APC transcripts, suggesting that the residual mutant transcripts were driven by other promoter(s). Furthermore, cap analysis of gene expression (CAGE) demonstrated that the deleted promoter 1B region is responsible for the great majority of APC transcription in many tissues except the brain. The deletion decreased the transcripts of APC-1B to 39-45% in the patient compared to the healthy controls, but it did not decrease those of APC-1A. Different deletions including promoter 1B have been reported in FAP patients. Taken together, our results strengthen the evidence that analysis of structural variations in promoter 1B should be considered for the FAP patients whose pathological mutations are not identified by conventional direct sequencing.

  20. Microtubule and Cell Contact Dependency of ER-bound PTP1B Localization in Growth Cones

    Science.gov (United States)

    Fuentes, Federico

    2009-01-01

    PTP1B is an ER-bound protein tyrosine phosphatase implied in the regulation of cell adhesion. Here we investigated mechanisms involved in the positioning and dynamics of PTP1B in axonal growth cones and evaluated the role of this enzyme in axons. In growth cones, PTP1B consistently localizes in the central domain, and occasionally at the peripheral region and filopodia. Live imaging of GFP-PTP1B reveals dynamic excursions of fingerlike processes within the peripheral region and filopodia. PTP1B and GFP-PTP1B colocalize with ER markers and coalign with microtubules at the peripheral region and redistribute to the base of the growth cone after treatment with nocodazole, a condition that is reversible. Growth cone contact with cellular targets is accompanied by invasion of PTP1B and stable microtubules in the peripheral region aligned with the contact axis. Functional impairment of PTP1B causes retardation of axon elongation, as well as reduction of growth cone filopodia lifetime and Src activity. Our results highlight the role of microtubules and cell contacts in the positioning of ER-bound PTP1B to the peripheral region of growth cones, which may be required for the positive role of PTP1B in axon elongation, filopodia stabilization, and Src activity. PMID:19158394

  1. Cloning, characterization, and expression analysis of the novel acetyltransferase retrogene Ard1b in the mouse.

    Science.gov (United States)

    Pang, Alan Lap-Yin; Peacock, Stephanie; Johnson, Warren; Bear, Deborah H; Rennert, Owen M; Chan, Wai-Yee

    2009-08-01

    N-alpha-terminal acetylation is a modification process that occurs cotranslationally on most eukaryotic proteins. The major enzyme responsible for this process, N-alpha-terminal acetyltransferase, is composed of the catalytic subunit ARD1A and the auxiliary subunit NAT1. We cloned, characterized, and studied the expression pattern of Ard1b (also known as Ard2), a novel homolog of the mouse Ard1a. Comparison of the genomic structures suggests that the autosomal Ard1b is a retroposed copy of the X-linked Ard1a. Expression analyses demonstrated a testis predominance of Ard1b. A reciprocal expression pattern between Ard1a and Ard1b is also observed during spermatogenesis, suggesting that Ard1b is expressed to compensate for the loss of Ard1a starting from meiosis. Both ARD1A and ARD1B can interact with NAT1 to constitute a functional N-alpha-terminal acetyltransferase in vitro. The expression of ARD1B protein can be detected in mouse testes but is delayed until the first appearance of round spermatids. In a cell culture model, the inclusion of the long 3' untranslated region of Ard1b leads to reduction of luciferase reporter activity, which implicates its role in translational repression of Ard1b during spermatogenesis. Our results suggest that ARD1B may have an important role in the later course of the spermatogenic process.

  2. Detection of genes regulated by Lmx1b during limb dorsalization.

    Science.gov (United States)

    Feenstra, Jennifer M; Kanaya, Kohei; Pira, Charmaine U; Hoffman, Sarah E; Eppey, Richard J; Oberg, Kerby C

    2012-05-01

    Lmx1b is a homeodomain transcription factor that regulates dorsal identity during limb development. Lmx1b knockout (KO) mice develop distal ventral-ventral limbs. Although induction of Lmx1b is linked to Wnt7a expression in the dorsal limb ectoderm, the downstream targets of Lmx1b that accomplish limb dorsalization are unknown. To identify genes targeted by Lmx1b, we compared gene arrays from Lmx1b KO and wild type mouse limbs during limb dorsalization, i.e., 11.5, 12.5, and 13.5 days post coitum. We identified 54 target genes that were differentially expressed in all three stages. Several skeletal targets, including Emx2, Matrilin1 and Matrilin4, demonstrated a loss of scapular expression in the Lmx1b KO mice, supporting a role for Lmx1b in scapula development. Furthermore, the relative abundance of extracellular matrix-related soft tissue targets regulated by Lmx1b, such as collagens and proteoglycans, suggests a mechanism that includes changes in the extracellular matrix composition to accomplish limb dorsalization. Our study provides the most comprehensive characterization of genes regulated by Lmx1b during limb development to-date and provides targets for further investigation. © 2012 The Authors. Development, Growth & Differentiation © 2012 Japanese Society of Developmental Biologists.

  3. Listeria monocytogenes and Shigella flexneri Activate the NLRP1B Inflammasome.

    Science.gov (United States)

    Neiman-Zenevich, Jana; Stuart, Sarah; Abdel-Nour, Mena; Girardin, Stephen E; Mogridge, Jeremy

    2017-11-01

    Activation of the innate immune receptor NLRP1B leads to the formation of an inflammasome, which induces autoproteolytic processing of pro-caspase-1, and ultimately to the release of inflammatory cytokines and to the execution of pyroptosis. One of the signals to which NLRP1B responds is metabolic stress that occurs in cells deprived of glucose or treated with metabolic inhibitors. NLRP1B might therefore sense microbial infection, as intracellular pathogens such as Listeria monocytogenes and Shigella flexneri cause metabolic stress as a result of nutrient scavenging and host cell damage. Here we addressed whether these pathogens activate the NLRP1B inflammasome. We found that Listeria infection activated the NLRP1B inflammasome in a reconstituted fibroblast model. Activation of NLRP1B by Listeria was diminished in an NLRP1B mutant shown previously to be defective at detecting energy stress and was dependent on the expression of listeriolysin O (LLO), a protein required for vacuolar escape. Infections of either Listeria or Shigella activated NLRP1B in the RAW264.7 murine macrophage line, which expresses endogenous NLRP1B. We conclude that NLRP1B senses cellular infection by distinct invasive pathogens. Copyright © 2017 American Society for Microbiology.

  4. LMX1B is essential for the maintenance of differentiated podocytes in adult kidneys.

    Science.gov (United States)

    Burghardt, Tillmann; Kastner, Jürgen; Suleiman, Hani; Rivera-Milla, Eric; Stepanova, Natalya; Lottaz, Claudio; Kubitza, Marion; Böger, Carsten A; Schmidt, Sarah; Gorski, Mathias; de Vries, Uwe; Schmidt, Helga; Hertting, Irmgard; Kopp, Jeffrey; Rascle, Anne; Moser, Markus; Heid, Iris M; Warth, Richard; Spang, Rainer; Wegener, Joachim; Mierke, Claudia T; Englert, Christoph; Witzgall, Ralph

    2013-11-01

    Mutations of the LMX1B gene cause nail-patella syndrome, a rare autosomal-dominant disorder affecting the development of the limbs, eyes, brain, and kidneys. The characterization of conventional Lmx1b knockout mice has shown that LMX1B regulates the development of podocyte foot processes and slit diaphragms, but studies using podocyte-specific Lmx1b knockout mice have yielded conflicting results regarding the importance of LMX1B for maintaining podocyte structures. In order to address this question, we generated inducible podocyte-specific Lmx1b knockout mice. One week of Lmx1b inactivation in adult mice resulted in proteinuria with only minimal foot process effacement. Notably, expression levels of slit diaphragm and basement membrane proteins remained stable at this time point, and basement membrane charge properties also did not change, suggesting that alternative mechanisms mediate the development of proteinuria in these mice. Cell biological and biophysical experiments with primary podocytes isolated after 1 week of Lmx1b inactivation indicated dysregulation of actin cytoskeleton organization, and time-resolved DNA microarray analysis identified the genes encoding actin cytoskeleton-associated proteins, including Abra and Arl4c, as putative LMX1B targets. Chromatin immunoprecipitation experiments in conditionally immortalized human podocytes and gel shift assays showed that LMX1B recognizes AT-rich binding sites (FLAT elements) in the promoter regions of ABRA and ARL4C, and knockdown experiments in zebrafish support a model in which LMX1B and ABRA act in a common pathway during pronephros development. Our report establishes the importance of LMX1B in fully differentiated podocytes and argues that LMX1B is essential for the maintenance of an appropriately structured actin cytoskeleton in podocytes.

  5. Listvenite logging on D/V CHIKYU: Hole BT1B, Oman Drilling Project

    Science.gov (United States)

    Kelemen, P. B.; Beinlich, A.; Morishita, T.; Greenberger, R. N.; Johnson, K. T. M.; Lafay, R.; Michibayashi, K.; Harris, M.; Phase I Science Party, T. O. D. P.

    2017-12-01

    Listvenite, quartz-carbonate altered ultramafic rock containing minor fuchsite (Cr-muscovite) forms by complete carbonation of peridotite and is thus an attractive objective for carbon mitigation studies. However, reaction controls and evolution of listvenite are still enigmatic. Here we present the first results of Phase 1 of the ICDP (International Continental Drilling Program) Oman Drilling Project and subsequent core logging using the analytical facilities on board the research vessel D/V CHIKYU. Hole BT1B contains 300 m of continuous drill core intersecting alluvium, listvenite-altered serpentinite, serpentinite, ophicarbonate and the underlying metamorphic sole of the Semail ophiolite, Oman. The drill core has been systematically investigated by visual core description, thin section petrography, X-ray fluorescence core logging, X-ray diffractometry, visible-shortwave infrared imaging spectroscopy and X-ray Computer Tomography. Our observations show that listvenite is highly variable in texture and color on the mm to m scale. Listvenite was visually categorized into 5 principal color groups: the dominant dark red (47 %), light red (19 %), orange (14 %), pale (2 %) and green (16 %). The presence of hematite/goethite results in dark reddish, red and orange hues. Light grey or pale colored listvenite lacks hematite and/or goethite veins and may represent the `true' listvenite. Green listvenite is characterized by the presence of cm-sized quartz-fuchsite intergrowths. Five zones of serpentinite, which vary in thickness between several tens of cm and 4 m, are intercalated within the massive listvenite of Hole BT1B. Gradational listvenite-serpentinite transition zones contain the ophicarbonate assemblage (magnesite + serpentine) and sometimes additional talc, representing intermediate carbonation reaction progress. Preservation of the former mesh texture and bastite after orthopyroxene in the listvenite suggest that the listvenite precursor had already been

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

    Science.gov (United States)

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

    2017-06-01

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

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

    Science.gov (United States)

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

    2015-11-15

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

  8. E4orf1 Limits the Oncolytic Potential of the E1B-55K Deletion Mutant Adenovirus▿

    Science.gov (United States)

    Thomas, Michael A.; Broughton, Robin S.; Goodrum, Felicia D.; Ornelles, David A.

    2009-01-01

    Clinical trials have shown oncolytic adenoviruses to be tumor selective with minimal toxicity toward normal tissue. The virus ONYX-015, in which the gene encoding the early region 1B 55-kDa (E1B-55K) protein is deleted, has been most effective when used in combination with either chemotherapy or radiation therapy. Therefore, improving the oncolytic nature of tumor-selective adenoviruses remains an important objective for improving this form of cancer therapy. Cells infected during the G1 phase of the cell cycle with the E1B-55K deletion mutant virus exhibit a reduced rate of viral late protein synthesis, produce fewer viral progeny, and are less efficiently killed than cells infected during the S phase. Here we demonstrate that the G1 restriction imposed on the E1B-55K deletion mutant virus is due to the viral oncogene encoded by open reading frame 1 of early region 4 (E4orf1). E4orf1 has been reported to signal through the phosphatidylinositol 3′-kinase pathway leading to the activation of Akt, mTOR, and p70 S6K. Evidence presented here shows that E4orf1 may also induce the phosphorylation of Akt and p70 S6K in a manner that depends on Rac1 and its guanine nucleotide exchange factor Tiam1. Accordingly, agents that have been reported to disrupt the Tiam1-Rac1 interaction or to prevent phosphorylation of the ribosomal S6 kinase partially alleviated the E4orf1 restriction to late viral protein synthesis and enhanced tumor cell killing by the E1B-55K mutant virus. These results demonstrate that E4orf1 limits the oncolytic nature of a conditionally replicating adenovirus such as ONYX-015. The therapeutic value of similar oncolytic adenoviruses may be improved by abrogating E4orf1 function. PMID:19129452

  9. E4orf1 limits the oncolytic potential of the E1B-55K deletion mutant adenovirus.

    Science.gov (United States)

    Thomas, Michael A; Broughton, Robin S; Goodrum, Felicia D; Ornelles, David A

    2009-03-01

    Clinical trials have shown oncolytic adenoviruses to be tumor selective with minimal toxicity toward normal tissue. The virus ONYX-015, in which the gene encoding the early region 1B 55-kDa (E1B-55K) protein is deleted, has been most effective when used in combination with either chemotherapy or radiation therapy. Therefore, improving the oncolytic nature of tumor-selective adenoviruses remains an important objective for improving this form of cancer therapy. Cells infected during the G(1) phase of the cell cycle with the E1B-55K deletion mutant virus exhibit a reduced rate of viral late protein synthesis, produce fewer viral progeny, and are less efficiently killed than cells infected during the S phase. Here we demonstrate that the G(1) restriction imposed on the E1B-55K deletion mutant virus is due to the viral oncogene encoded by open reading frame 1 of early region 4 (E4orf1). E4orf1 has been reported to signal through the phosphatidylinositol 3'-kinase pathway leading to the activation of Akt, mTOR, and p70 S6K. Evidence presented here shows that E4orf1 may also induce the phosphorylation of Akt and p70 S6K in a manner that depends on Rac1 and its guanine nucleotide exchange factor Tiam1. Accordingly, agents that have been reported to disrupt the Tiam1-Rac1 interaction or to prevent phosphorylation of the ribosomal S6 kinase partially alleviated the E4orf1 restriction to late viral protein synthesis and enhanced tumor cell killing by the E1B-55K mutant virus. These results demonstrate that E4orf1 limits the oncolytic nature of a conditionally replicating adenovirus such as ONYX-015. The therapeutic value of similar oncolytic adenoviruses may be improved by abrogating E4orf1 function.

  10. The design strategy of selective PTP1B inhibitors over TCPTP.

    Science.gov (United States)

    Li, XiangQian; Wang, LiJun; Shi, DaYong

    2016-08-15

    Protein tyrosine phosphatase 1B (PTP1B) has already been well studied as a highly validated therapeutic target for diabetes and obesity. However, the lack of selectivity limited further studies and clinical applications of PTP1B inhibitors, especially over T-cell protein tyrosine phosphatase (TCPTP). In this review, we enumerate the published specific inhibitors of PTP1B, discuss the structure-activity relationships by analysis of their X-ray structures or docking results, and summarize the characteristic of selectivity related residues and groups. Furthermore, the design strategy of selective PTP1B inhibitors over TCPTP is also proposed. We hope our work could provide an effective way to gain specific PTP1B inhibitors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Mutations in STX1B, encoding a presynaptic protein, cause fever-associated epilepsy syndromes

    DEFF Research Database (Denmark)

    Schubert, J.; Siekierska, A.; Langlois, M.

    2014-01-01

    Febrile seizures affect 2-4% of all children(1) and have a strong genetic component(2). Recurrent mutations in three main genes (SCN1A, SCN1B and GABRG2)(3-5) have been identified that cause febrile seizures with or without epilepsy. Here we report the identification of mutations in STX1B, encoding...... syntaxin-1B(6), that are associated with both febrile seizures and epilepsy. Whole-exome sequencing in independent large pedigrees(7,8) identified cosegregating STX1B mutations predicted to cause an early truncation or an in-frame insertion or deletion. Three additional nonsense or missense mutations...... and a de novo microdeletion encompassing STX1B were then identified in 449 familial or sporadic cases. Video and local field potential analyses of zebrafish larvae with antisense knockdown of stx1b showed seizure-like behavior and epileptiform discharges that were highly sensitive to increased temperature...

  12. The Function of PTP1B in Neuroendocrine Differentation of Prostate Cancer

    Science.gov (United States)

    2009-01-01

    AD_________________ Award Number: W81XWH-07-1-0061 TITLE: The Function of PTP1B in Neuroendocrine...The Function of PTP1B in Neuroendocrine Differentation of Prostate Cancer 5b. GRANT NUMBER W81XWH-07-1-0061 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR...pathways that may be responsible for the neuroendocrine differentiation of prostate cancer cells, particularly the relationship of PTP1B to IL-8

  13. PTP1B promotes aggressiveness of breast cancer cells by regulating PTEN but not EMT.

    Science.gov (United States)

    Liu, Xue; Chen, Qian; Hu, Xu-Gang; Zhang, Xian-Chao; Fu, Ti-Wei; Liu, Qing; Liang, Yan; Zhao, Xi-Long; Zhang, Xia; Ping, Yi-Fang; Bian, Xiu-Wu

    2016-10-01

    Metastasis is a complicated, multistep process and remains the major cause of cancer-related mortality. Exploring the molecular mechanisms underlying tumor metastasis is crucial for development of new strategies for cancer prevention and treatment. In this study, we found that protein tyrosine phosphatase 1B (PTP1B) promoted breast cancer metastasis by regulating phosphatase and tensin homolog (PTEN) but not epithelial-mesenchymal transition (EMT). By detecting PTP1B expression of the specimens from 128 breast cancer cases, we found that the level of PTP1B was higher in breast cancer tissues than the corresponding adjacent normal tissues. Notably, PTP1B was positively associated with lymph node metastasis (LNM) and estrogen receptor (ER) status. In vitro, disturbing PTP1B expression obviously attenuated cell migration and invasion. On the contrary, PTP1B overexpression significantly increased migration and invasion of breast cancer cells. Mechanistically, PTP1B knockdown upregulated PTEN, accompanied with an abatement of AKT phosphorylation and the expression of matrix metalloproteinase 2 (MMP2) and MMP7. Conversely, forced expression of PTP1B reduced PTEN and increased AKT phosphorylation as well as the expression of MMP2 and MMP7. Notably, neither EMT nor stemness of breast cancer cells was regulated by PTP1B. We also found that PTP1B acted as an independent prognostic factor and predicted poor prognosis in ER-positive breast cancer patients. Taken together, our findings provide advantageous evidence for the development of PTP1B as a potential therapeutic target for breast cancer, especially for ER-positive breast cancer patients.

  14. Yersinia pestis Requires Host Rab1b for Survival in Macrophages.

    Directory of Open Access Journals (Sweden)

    Michael G Connor

    2015-10-01

    Full Text Available Yersinia pestis is a facultative intracellular pathogen that causes the disease known as plague. During infection of macrophages Y. pestis actively evades the normal phagosomal maturation pathway to establish a replicative niche within the cell. However, the mechanisms used by Y. pestis to subvert killing by the macrophage are unknown. Host Rab GTPases are central mediators of vesicular trafficking and are commonly targeted by bacterial pathogens to alter phagosome maturation and killing by macrophages. Here we demonstrate for the first time that host Rab1b is required for Y. pestis to effectively evade killing by macrophages. We also show that Rab1b is specifically recruited to the Yersinia containing vacuole (YCV and that Y. pestis is unable to subvert YCV acidification when Rab1b expression is knocked down in macrophages. Furthermore, Rab1b knockdown also altered the frequency of association between the YCV with the lysosomal marker Lamp1, suggesting that Rab1b recruitment to the YCV directly inhibits phagosome maturation. Finally, we show that Rab1b knockdown also impacts the pH of the Legionella pneumophila containing vacuole, another pathogen that recruits Rab1b to its vacuole. Together these data identify a novel role for Rab1b in the subversion of phagosome maturation by intracellular pathogens and suggest that recruitment of Rab1b to the pathogen containing vacuole may be a conserved mechanism to control vacuole pH.

  15. SUMOylation of the ING1b tumor suppressor regulates gene transcription

    DEFF Research Database (Denmark)

    Satpathy, Shankha; Guérillon, Claire; Kim, Tae-Sun

    2014-01-01

    members of histone deacetylase complexes, whereas ING3-5 are stoichiometric components of different histone acetyltransferase complexes. The INGs target these complexes to histone marks, thus acting as epigenetic regulators. ING proteins affect angiogenesis, apoptosis, DNA repair, metastasis......1b E195A), we further demonstrate that ING1b SUMOylation regulates the binding of ING1b to the ISG15 and DGCR8 promoters, consequently regulating ISG15 and DGCR8 transcription. These results suggest a role for ING1b SUMOylation in the regulation of gene transcription....

  16. MTNR1B G24E variant associates With BMI and fasting plasma glucose in the general population in studies of 22,142 Europeans

    DEFF Research Database (Denmark)

    Andersson, Ehm A; Holst, Birgitte; Sparsø, Thomas

    2010-01-01

    OBJECTIVE: Common variants in the melatonin receptor type 1B (MTNR1B) locus have been shown to increase fasting plasma glucose (FPG) and the risk of type 2 diabetes. The aims of this study were to evaluate whether nonsynonymous variants in MTNR1B associate with monogenic forms of hyperglycemia...... specific, and none of the investigated MTNR1B variants associated with type 2 diabetes. The common 24E variant associated with increased prevalence of obesity (odds ratio 1.20 [1.08-1.34]; P = 8.3 x 10(-4)) and increased BMI (beta = 0.5 kg/m(2); P = 1.2 x 10(-5)) and waist circumference (beta = 1.2 cm; P...

  17. Radioimmunological determination of plasma testosterone, luteinizing hormone, folliculostimulating hormone and prolactin levels in patients with prostate cancer

    International Nuclear Information System (INIS)

    Milkov, V.; Maleeva, A.; Tsvetkov, M.; Visheva, N.

    1986-01-01

    The hormone levels were measured before and after hormonal therapy. Statistically significant changes in the levels of the hormones in this study were recognized (p<0,001) as a result of treatment with estrogen preparations. Plasma prolactin was raised before estrogen therapy (statistically significant rise, p<0,001), as compared to the levels in a control group of normal subjects. A mild tendency was observed toward its increase, depending on the duration of treatment. The results of this study show that control of the hormonal status of patients with prostate cancer may serve as reliable criterion in evaluating the effectiveness of hormonal therapy. The changes in prolactin levels are evidence of hormonal disbalance, which may be observed in these patients

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

    International Nuclear Information System (INIS)

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

    1987-01-01

    A specific homologous radioimmunoassay was developed to measure rabbit β-casein in rabbit mammary gland with a sensitivity of 0.5 ng/ml protein. It was used to measure casein concentration during pregnancy and in organ culture of mammary gland explants. Casein was detectable in virgin mammary glands, showed a small increase during the first half of pregnancy, increased more than 20-fold between Days 21 and 27, and diminished somewhat on the first days of lactation. After 24 hr of culture, mammary gland explants had no detectable casein, but the addition of increasing concentrations of prolactin to a culture medium which contained insulin (5 μg/ml) and cortisol (0.5 μg/ml) induced a regular increase in the casein content of the tissue. Casein started to increase when 10 ng/ml of prolactin was present and maximal values were achieved for 100 ng/ml of the hormone

  19. Lactation Induction in a Commissioned Mother by Surrogacy: Effects on Prolactin Levels, Milk Secretion and Mother Satisfaction.

    Science.gov (United States)

    Zingler, Emilie; Amato, Angélica Amorim; Zanatta, Alysson; Vogt, Maria de Fátima Brito; Wanderley, Miriam da Silva; Mariani Neto, Coríntio; Zaconeta, Alberto Moreno

    2017-02-01

    Case report of a 39-year-old intended mother of a surrogate pregnancy who underwent induction of lactation by sequential exposure to galactagogue drugs (metoclopramide and domperidone), nipple mechanical stimulation with an electric pump, and suction by the newborn. The study aimed to analyze the effect of each step of the protocol on serum prolactin levels, milk secretion and mother satisfaction, in the set of surrogacy. Serum prolactin levels and milk production had no significant changes. Nevertheless, the mother was able to breastfeed for four weeks, and expressed great satisfaction with the experience. As a conclusion, within the context of a surrogate pregnancy, breastfeeding seems to bring emotional benefits not necessarily related to an increase in milk production. Thieme-Revinter Publicações Ltda Rio de Janeiro, Brazil.

  20. No significant effect of the SLCO1B1 polymorphism on the pharmacokinetics of ursodeoxycholic acid.

    Science.gov (United States)

    Xiang, Xiaoqiang; Vakkilainen, Juha; Backman, Janne T; Neuvonen, Pertti J; Niemi, Mikko

    2011-11-01

    To investigate possible effects of the SLCO1B1 polymorphism on the pharmacokinetics of ursodeoxycholic acid (UDCA) and its metabolites in healthy volunteers. In a crossover study with two phases, 15 healthy volunteers with the SLCO1B1*1A/*1A genotype, seven with the *1B/*1B genotype, and five with the *15/*15 or *5/*15 genotype ingested placebo or a single 150-mg dose of UDCA. Plasma concentrations of bile acids and their biosynthesis marker were determined up to 24 h post-ingestion by liquid chromatography-tandem mass spectrometry. The SLCO1B1 genotype had no significant effect on the pharmacokinetics of UDCA. The geometric mean ratios (95% confidence interval) of UDCA area under the plasma concentration-time curve from 0 to 12 h (AUC(0-12)) in subjects with the SLCO1B1*1B/*1B genotype and in subjects with the SLCO1B1*15/*15 or *5/*15 genotype to the AUC(0-12) in subjects with the SLCO1B1*1A/*1A genotype were 1.07 (0.85, 1.35; P = 0.459) and 0.93 (0.75, 1.15; P = 0.563), respectively. In addition, following either placebo or UDCA administration, the SLCO1B1 polymorphism showed no association with the AUC(0-24) of the glycine and taurine conjugates of UDCA, with endogenous bile acids, or with the incremental AUC(0-24) of a bile acid synthesis marker. Compared with placebo, UDCA ingestion increased the AUC(0-24) of cholic acid, glycochenodeoxycholic acid, glycocholic acid, and glycodeoxycholic acid by 1.5-, 1.1-, 1.2-, and 1.2- fold (P acids.

  1. Steered Molecular Dynamics for Investigating the Interactions Between Insulin Receptor Tyrosine Kinase (IRK) and Variants of Protein Tyrosine Phosphatase 1B (PTP1B).

    Science.gov (United States)

    Nguyen, Hung; Do, Nhat; Phan, Tuyn; Pham, Tri

    2018-02-01

    The aim of this study is to use steered molecular dynamics to investigate the dissociation process between IRK and PTP1Bs for wild type and five mutants (consisting of p.D181E, p.D181A, p.Q262A, p.D181A-Y46F, and p.D181A-Q262A). The gained results are observed not only the unbinding mechanism of IRK-PTP1B complexes came from pulling force profile, number of hydrogen bonds, and interaction energy between IRK and PTP1Bs but also described PTP1B's point mutations could variably change its binding affinity towards IRK. Additionally, the binding free energy calculated by Molecular Mechanics/Poisson-Boltzmann Surface Area (MM-PBSA) is also revealed that electrostatic energy and polar solvation energy mainly made up the binding free energy of PTP1B-IRK complexes.

  2. Defective distal regulatory element at the 5' upstream of rat prolactin gene of steroid-nonresponsive GH-subclone.

    Science.gov (United States)

    Kumar, V; Wong, D T; Pasion, S G; Biswas, D K

    1987-12-08

    The prolactin-nonproducing (PRL-) GH cell strains (rat pituitary tumor cells in culture). GH12C1 and F1BGH12C1, do not respond to steroid hormones estradiol or hydrocortisone (HC). However, the stimulatory effect of estradiol and the inhibitory effect of hydrocortisone on prolactin synthesis can be demonstrated in the prolactin-producing GH cell strain, GH4C1. In this investigation we have examined the 5' end flanking region of rat prolactin (rat PRL) gene of steroid-responsive, GH4C1 cells to identify the positive and negative regulatory elements and to verify the status of these elements in steroid-nonresponsive F1BGH12C1 cells. Results presented in this report demonstrate that the basel level expression of the co-transferred Neo gene (neomycin phosphoribosyl transferase) is modulated by the distal upstream regulatory elements of rat PRL gene in response to steroid hormones. The expression of adjacent Neo gene is inhibited by dexamethasone and is stimulated by estradiol in transfectants carrying distal regulatory elements (SRE) of steroid-responsive cells. These responses are not observed in transfectants with the rat PRL upstream sequences derived from steroid-nonresponsive cells. The basal level expression of the host cell alpha-2 tubulin gene is not affected by dexamethasone. We report here the identification of the distal steroid regulatory element (SRE) located between 3.8 and 7.8 kb upstream of the transcription initiation site of rat PRL gene. Both the positive and the negative effects of steroid hormones can be identified within this upstream sequence. This distal SRE appears to be nonfunctional in steroid-nonresponsive cells. Though the proximal SRE is functional, the defect in the distal SRE makes the GH substrain nonresponsive to steroid hormones. These results suggest that both the proximal and the distal SREs are essential for the mediation of action of steroid hormones in GH cells.

  3. Pharmacological characterization of lipidized analogs of prolactin-releasing peptide with a modified C-terminal aromatic ring

    Czech Academy of Sciences Publication Activity Database

    Pražienková, Veronika; Tichá, Anežka; Blechová, Miroslava; Špolcová, Andrea; Železná, Blanka; Maletínská, Lenka

    2016-01-01

    Roč. 67, č. 1 (2016), s. 121-128 ISSN 0867-5910 R&D Projects: GA ČR(CZ) GA15-08679S Institutional support: RVO:61388963 Keywords : prolactin-releasing peptide * blood-brain barrier * food intake * lipidization * phenylalanine derivatives Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 2.883, year: 2016 http://www.jpp.krakow.pl/journal/archive/02_16/articles/11_article.html

  4. Plasma Concentration of Prolactin, Testosterone Might Be Associated with Brain Response to Visual Erotic Stimuli in Healthy Heterosexual Males

    OpenAIRE

    Seo, Younghee; Jeong, Bumseok; Kim, Ji-Woong; Choi, Jeewook

    2009-01-01

    Objective Many studies have showed that excess or lack of sexual hormones, such as prolactin and testosterone, induced the sexual dysfunction in humans. Little, however, is known about the role of sexual hormones showing normal range in, especially, the basal state unexposed to any sexual stimulation. We hypothesized sexual hormones in the basal state may affect sexual behavior. Methods We investigated the association of the sexual hormones level in the basal hormonal state before visual sexu...

  5. EFFECT OF MASSAGE AND AROMATHERAPY ON STRESS AND PROLACTIN LEVEL AMONG PRIMIPAROUS PUERPERAL MOTHERS IN SEMARANG, CENTRAL JAVA, INDONESIA

    Directory of Open Access Journals (Sweden)

    Melyana Nurul Widyawati

    2016-08-01

    Full Text Available Background: Exclusive breastfeeding in Semarang during the past five years remains low. Only 20 to 64% of mothers were breastfed exclusively in 2010-2012. The incidence of postpartum blues was reported by 29.9% mothers, and mostly (56.6% was primiparous. Objective: This study aims to determine the effect of Loving Massage, aromatherapy, and a combination of Loving Massage and aromatherapy on stress levels, and changes in levels of prolactin in primiparous puerperal in Semarang. Method: A true experimental study with a randomized pretest-posttest control group design. Cluster random sampling was used to select 12 health centers from the 37 health centers in Semarang. A random assignment with a sealed envelope was performed to divide study participants into four groups; loving massage group, aromatherapy group, and a combination group of loving massage and aromatherapy, and a control group. A total of 52 primiparous puerperal mothers was involved, with 13 mothers were distributed equally in each group. Results: Loving Massage, aromatherapy, and a combination of Loving Massage and aromatherapy effectively changed mother’s stress and prolactin levels. Effectiveness of each treatment assessed from the average difference in scores before and after treatment. Combination of Loving Massage and aromatherapy had proven as the most effective treatment in reducing stress levels (11.61 ± 6.76, and increasing prolactin level (83.13 ± 6.41 ng/ml. Conclusions: Loving Massage & Aromatherapy shown to lower the levels of stress, and can increase the levels prolactin in postpartum primiparous. Therefore, it is recommended to provide Loving Massage therapy and aromatherapy to postpartum primiparous mothers.

  6. THE IMPACT OF CONSUMING AMARANTHUS SPINOSUS L EXTRACT ON PROLACTIN LEVEL AND BREAST MILK PRODUCTION IN POSTPARTUM MOTHERS

    Directory of Open Access Journals (Sweden)

    Okta Kuswaningrum

    2017-10-01

    Full Text Available Background: Breast milk is the best natural nutrient for the baby. However, some mothers have problems with breastfeeding due to lack of breast milk production. Spinach leaf (Amaranthus Spinosus L is considered as one of the plants that have the effect of non-synthesis lactagogues to increase milk production. Objective: To analysis the effect of spinach leaf (Amaranthus Spinosus L extract on prolactin and breast milk production in postpartum mothers. Methods: This was a quasy-experimental study with pretest posttest with control group design conducted in the Community Health Center of Wonogiri II from December 2016 to January 2017. There were 30 participants were selected using purposive sampling, with 15 participants assigned in the experiment and control group. Data were analyzed using independent and paired t-test. Results: The results showed significant differences in prolactin levels (p = 0.000, breast milk production (p = 0.000, and infant weight (p = 0.000 (<0.05 after given spinach leaf (Amaranthus Spinosus L extract. Conclusion: Spinach leaf (Amaranthus Spinosus L extract had a significant effect in increasing the prolactin levels and breast milk production in postpartum mothers.

  7. Placental Barrier and Autism Spectrum Disorders: The Role of Prolactin and Dopamine on the Developing Fetal Brain.

    Science.gov (United States)

    Yarlagadda, Atmaram; Acharya, Ganesh; Kasaraneni, Jayaprada; Hampe, Christiane S; Clayton, Anita H

    2015-01-01

    Dopamine and prolactin exhibit opposite effects on lactation. However, a possible role for increased prolactin/dopamine ratio in postpartum mood and thought disorders and as a prognostic indicator of the mother's future mental health has not been well investigated. Postpartum depression is a serious condition with potentially devastating outcomes for both the mother and the infant. Early detection and treatment of this condition can have impressive results. Treatment options include antidepressant medications for mood disorders and use of antipsychotics and electroconvulsive therapy to address postpartum psychosis. Although there are obvious benefits of such treatments on the welfare of the mother and her child, broader implications of these treatments on lactation and child growth and development are not known. This review article explores a possible link between in-utero exposure to a high maternal prolactin/dopamine ratio and subsequent development of autism spectrum disorders. We hypothesize that a comprehensive, biologically oriented approach to the use of psychotropics in the regulation of neurotransmission during pre- and postpartum periods may result in better outcomes in this population.

  8. Extending the Impact of RAC1b Overexpression to Follicular Thyroid Carcinomas

    Directory of Open Access Journals (Sweden)

    Márcia Faria

    2016-01-01

    Full Text Available RAC1b is a hyperactive variant of the small GTPase RAC1 known to be a relevant molecular player in different cancers. Previous studies from our group lead to the evidence that its overexpression in papillary thyroid carcinoma (PTC is associated with an unfavorable prognosis. In the present study, we intended to extend the analysis of RAC1b expression to thyroid follicular neoplasms and to seek for clinical correlations. RAC1b expression levels were determined by RT-qPCR in thyroid follicular tumor samples comprising 23 follicular thyroid carcinomas (FTCs and 33 follicular thyroid adenomas (FTAs. RAC1b was found to be overexpressed in 33% of carcinomas while no RAC1b overexpression was documented among follicular adenomas. Patients with a diagnosis of FTC were divided into two groups based on longitudinal evolution and final outcome. RAC1b overexpression was significantly associated with both the presence of distant metastases (P = 0.01 and poorer clinical outcome (P = 0.01 suggesting that, similarly to that previously found in PTCs, RAC1b overexpression in FTCs is also associated with worse outcomes. Furthermore, the absence of RAC1b overexpression in follicular adenomas hints its potential as a molecular marker likely to contribute, in conjunction with other putative markers, to the preoperative differential diagnosis of thyroid follicular lesions.

  9. Structural basis for inhibition of the protein tyrosine phosphatase 1B by phosphotyrosine peptide mimetics

    NARCIS (Netherlands)

    Groves, M R; Yao, Z J; Roller, P P; Burke, T R; Barford, D

    1998-01-01

    Protein tyrosine phosphatases regulate diverse cellular processes and represent important targets for therapeutic intervention in a number of diseases. The crystal structures of protein tyrosine phosphatase 1B (PTP1B) in complex with small molecule inhibitors based upon two classes of

  10. PTP1B inhibitor promotes endothelial cell motility by activating the DOCK180/Rac1 pathway.

    Science.gov (United States)

    Wang, Yuan; Yan, Feng; Ye, Qing; Wu, Xiao; Jiang, Fan

    2016-04-07

    Promoting endothelial cell (EC) migration is important not only for therapeutic angiogenesis, but also for accelerating re-endothelialization after vessel injury. Several recent studies have shown that inhibition of protein tyrosine phosphatase 1B (PTP1B) may promote EC migration and angiogenesis by enhancing the vascular endothelial growth factor receptor-2 (VEGFR2) signalling. In the present study, we demonstrated that PTP1B inhibitor could promote EC adhesion, spreading and migration, which were abolished by the inhibitor of Rac1 but not RhoA GTPase. PTP1B inhibitor significantly increased phosphorylation of p130Cas, and the interactions among p130Cas, Crk and DOCK180; whereas the phosphorylation levels of focal adhesion kinase, Src, paxillin, or Vav2 were unchanged. Gene silencing of DOCK180, but not Vav2, abrogated the effects of PTP1B inhibitor on EC motility. The effects of PTP1B inhibitor on EC motility and p130Cas/DOCK180 activation persisted in the presence of the VEGFR2 antagonist. In conclusion, we suggest that stimulation of the DOCK180 pathway represents an alternative mechanism of PTP1B inhibitor-stimulated EC motility, which does not require concomitant VEGFR2 activation as a prerequisite. Therefore, PTP1B inhibitor may be a useful therapeutic strategy for promoting EC migration in cardiovascular patients in which the VEGF/VEGFR functions are compromised.

  11. Interleukin 1B variant -1473G/C (rs1143623) influences triglyceride and interleukin 6 metabolism

    Science.gov (United States)

    Interleukin 1b (IL1B or IL-1ß), is a key modulator of the immune response which exerts its functions mainly via interleukin 6 (IL6) regulation. Fatty meals cause transient hypertriglyceridemia and are considered to be proinflammatory, but the extent of these responses shows high interindividual susc...

  12. Data of evolutionary structure change: 1B26D-1AUPA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B26D-1AUPA 1B26 1AUP D A ------------------SLYEMAVEQFN----RA----...ine> GLU CA 284 LEU CA 369 1AUP A 1AUPA DPEGITTEEKINY ALA CA 419 ALA CA 500 1AUP... A 1AUPA RYGLGYNLVAGA

  13. Tissue-specific alternative splicing and expression of ATP1B2 gene ...

    African Journals Online (AJOL)

    After heat-stress, the expression levels of the different transcripts were lower in different tissues; however, the expression of the ATP1B2-complete transcript increased in heart and lung tissues. The results of this research provide some useful information for further studies into the function of the bovine ATP1B2 gene.

  14. Data of evolutionary structure change: 1B9OA-1LAAA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B9OA-1LAAA 1B9O 1LAA A A KQFTKCELSQLLKDI--DGYGGIALPELICTMFHTSGYD...pdbChain> 1LAAA TLKRLGMDGYRG HHHH GGG...Chain>A 1LAAA TNYNAGDRSTEY1LAA A 1LAAA RVVRDPQGIRA ...>A 1LAAA NRCQNRDVRQY H GGG

  15. Data of evolutionary structure change: 1B0FA-2FOCA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B0FA-2FOCA 1B0F 2FOC A A IVGGRRARPHAWPFMVSLQLA----GGHFCGATLIAPNF...>2FOC A 2FOCA SLQYRSGSSWAHTC ...tryChain> 2FOC A 2FOCA PLHCLVNGQY...ine> 2FOC A 2FOCA...in>A 2FOCA HCVDR--ELTFR GG

  16. Molecular characterization of cytochrome P450 1B1 and effect of ...

    African Journals Online (AJOL)

    CYP1B which belongs to the cytochrome P450 superfamily of genes, is involved in the oxidation of endogenous and exogenous compounds, and could potentially be a useful biomarker in fish for exposure to arylhydrocarbon receptors (AhR) ligands. In this study, a new complementary DNA (cDNA) of the CYP1B subfamily ...

  17. Extending the Impact of RAC1b Overexpression to Follicular Thyroid Carcinomas

    Science.gov (United States)

    Faria, Márcia; Capinha, Liliana; Simões-Pereira, Joana; Bugalho, Maria João; Silva, Ana Luísa

    2016-01-01

    RAC1b is a hyperactive variant of the small GTPase RAC1 known to be a relevant molecular player in different cancers. Previous studies from our group lead to the evidence that its overexpression in papillary thyroid carcinoma (PTC) is associated with an unfavorable prognosis. In the present study, we intended to extend the analysis of RAC1b expression to thyroid follicular neoplasms and to seek for clinical correlations. RAC1b expression levels were determined by RT-qPCR in thyroid follicular tumor samples comprising 23 follicular thyroid carcinomas (FTCs) and 33 follicular thyroid adenomas (FTAs). RAC1b was found to be overexpressed in 33% of carcinomas while no RAC1b overexpression was documented among follicular adenomas. Patients with a diagnosis of FTC were divided into two groups based on longitudinal evolution and final outcome. RAC1b overexpression was significantly associated with both the presence of distant metastases (P = 0.01) and poorer clinical outcome (P = 0.01) suggesting that, similarly to that previously found in PTCs, RAC1b overexpression in FTCs is also associated with worse outcomes. Furthermore, the absence of RAC1b overexpression in follicular adenomas hints its potential as a molecular marker likely to contribute, in conjunction with other putative markers, to the preoperative differential diagnosis of thyroid follicular lesions. PMID:27127508

  18. The ARID1B phenotype: what we have learned so far.

    Science.gov (United States)

    Santen, Gijs W E; Clayton-Smith, Jill

    2014-09-01

    Evidence is now accumulating from a number of sequencing studies that ARID1B not only appears to be one of the most frequently mutated intellectual disability (ID) genes, but that the range of phenotypes caused by ARID1B mutations seems to be extremely wide. Thus, it is one of the most interesting ID genes identified so far in the exome sequencing era. In this article, we review the literature surrounding ARID1B and attempt to delineate the ARID1B phenotype. The vast majority of published ARID1B patients have been ascertained through studies of Coffin-Siris syndrome (CSS), which leads to bias when documenting the frequencies of phenotypic features. Additional observations of those individuals ascertained through exome sequencing studies helps in delineation of the broader clinical phenotype. We are currently establishing an ARID1B consortium, aimed at collecting ARID1B patients identified through genome-wide sequencing strategies. We hope that this endeavor will eventually lead to a more comprehensive view of the ARID1B phenotype. © 2014 Wiley Periodicals, Inc.

  19. The histone demethylase Jarid1b is required for hematopoietic stem cell self-renewal

    DEFF Research Database (Denmark)

    Stewart, Morag H; Albert, Mareike; Sroczynska, Patrycja

    2015-01-01

    Jarid1b/KDM5b is a histone demethylase that regulates self-renewal and differentiation in stem cells and cancer, however its function in hematopoiesis is unclear. Here, we find that Jarid1b is highly expressed in primitive hematopoietic compartments and is overexpressed in acute myeloid leukemias...... compromises hematopoietic stem cell (HSC) self-renewal capacity and suggest that Jarid1b is a positive regulator of HSC potential.......Jarid1b/KDM5b is a histone demethylase that regulates self-renewal and differentiation in stem cells and cancer, however its function in hematopoiesis is unclear. Here, we find that Jarid1b is highly expressed in primitive hematopoietic compartments and is overexpressed in acute myeloid leukemias....... Constitutive genetic deletion of Jarid1b did not impact steady-state hematopoiesis. In contrast, acute deletion of Jarid1b from bone marrow increased peripheral blood T cells and, following secondary transplantation, resulted in loss of bone marrow reconstitution. Our results reveal that deletion of Jarid1b...

  20. Pterocarpans with inhibitory effects on protein tyrosine phosphatase 1B from Erythrina lysistemon Hutch

    DEFF Research Database (Denmark)

    Dao, Trong Tuan; Nguyen, Phi Hung; Thuong, Phuong Thien

    2009-01-01

    ',5':3,4]-2'',2''-dimethyldihydropyrano[6'',5'':9,10]pterocarpan (1), furano[5',4':3,4]-9-hydroxy-10-prenylpterocarpan (2), and 8-formyl-3,9-dihydroxy-4,10-diprenylpterocarpan (3), based on spectroscopic analyses. All the isolates, with the exception of 3, 6, and 11, strongly inhibited protein tyrosine phosphatase 1B (PTP1B) activity...

  1. An homologous human prolactin (hPRL) radioimmunoassay with an antibody against ''little'' hPRL

    International Nuclear Information System (INIS)

    Werder, K. von; Felixberger, F.; Gottsmann, M.; Kerner, W.; Gloeckner, B.

    1978-01-01

    Since it is tedious to prepare prolactin (PRL) from human pituitaries that is sufficiently pure for immunization, the authors have used the serum of a male patient with complete panhypopituitarism, a PRL-producing pituitary tumour and excessively high hPRL-levels (18-20μg per ml) as a source of the antigen. Ten millilitres of serum were passed through 3cm x 110cm Sephadex G-75 columns. The ''big'' hPRL (20% of the total immunoreactivity) was discarded and the ''little'' hPRL (80%) from two chromatographic runs was lyophilized (approximately 50μg hPRL) and injected into a rabbit together with 1ml of Freund's adjuvant. Though the polyacrylamide gel electrophoresis of the preparation showed a marked protein heterogeneity, labelling of this material with 125 I and subsequent Sephadex G-50 and G-75 chromatography led to an elution pattern comparable to that of 125 I-VLS-hPRL. Specific hPRL antibodies could be demonstrated after three injections. After nine injections the binding (B 0 ) of 125 I-hPRL at a final antibody dilution of 1:100,000 was 22.5%. This dilution was suitable for a highly specific prolactin radioimmunoassay (hPRL RIA) with a lower limit of detection (B 0 minus 3SD) below 0.1ng of VLS-hPRL and a maximal inhibition of tracer binding when 10ng of unlabelled hPRL were added. No cross-reaction with hGH, hPL, hFSH, hLH or hTSH was found. Dilution curves of galactorrhea serum, pregnancy serum, and ''big'' and ''little'' hPRL preparations from serum were shown to run parallel to the standard curve. For routine measurements, pooled pregnancy serum was calibrated with the MRC standard A-71/222 and used as standard in the RIA (1ng of VLS-hPRL equals 20μU of 71/222hPRL). These findings show that serum of a patient hyperprolactinaemia and panhypopituitarism can be an ideal source of the hPRL immunogen since, in contrast to pituitary extracts, no separation from other contaminating anterior pituitary hormones is needed. (author)

  2. Protein tyrosine phosphatase, PTP1B, expression and activity in rat corneal endothelial cells

    Science.gov (United States)

    Harris, Deshea L.

    2007-01-01

    Purpose The current studies were conducted to determine whether the protein tyrosine phosphatase, PTP1B, plays a role in regulating epidermal growth factor receptor (EGFR) Tyr992 phosphorylation and cell cycle entry in rat corneal endothelial cells. Methods Corneas were obtained from male Sprague-Dawley rats. PTP1B mRNA and protein expression were compared in confluent and subconfluent cells by RT-PCR and western blots. Immunocytochemistry was used to determine the subcellular localization of both PTP1B and EGFR following epidermal growth factor (EGF) stimulation. Western blots were used to analyze the time-dependent effect of EGF on phosphorylation of EGFR Tyr992 plus or minus CinnGEL 2Me, an inhibitor of PTP1B activity. The effect of PTP1B inhibition on cell cycle entry was determined by calculating the percent of Ki67-positive cells following EGF treatment. Results PTP1B mRNA expression was similar in confluent and subconfluent cells, but PTP1B protein was expressed at 3 fold higher levels in subconfluent cells. Positive staining for PTP1B was localized in vesicular structures below the plasma membrane. EGFR staining was located at cell-cell borders in untreated endothelium, but was mainly cytoplasmic by 15 min after EGF treatment. In control cultures, phosphorylation of EGFR Tyr992 peaked by 5 min following EGF stimulation and rapidly decreased to basal levels by 30 min. In cultures pretreated with CinnGEL 2Me, Tyr992 phosphorylation peaked 2 min following EGF addition and was consistently sustained at a higher level than controls until 60 min after treatment. By 18 h following EGF treatment, cultures pretreated with CinnGEL 2Me exhibited a 1.7 fold increase in the number of Ki67-positive cells compared with control cultures. Conclusions Comparison of PTP1B mRNA and protein levels indicates that PTP1B expression is regulated mainly at the protein level and is higher in subconfluent cells. PTP1B was located in vesicles below the plasma membrane. The fact that

  3. Harnessing insulin- and leptin-induced oxidation of PTP1B for therapeutic development.

    Science.gov (United States)

    Krishnan, Navasona; Bonham, Christopher A; Rus, Ioana A; Shrestha, Om Kumar; Gauss, Carla M; Haque, Aftabul; Tocilj, Ante; Joshua-Tor, Leemor; Tonks, Nicholas K

    2018-01-18

    The protein tyrosine phosphatase PTP1B is a major regulator of glucose homeostasis and energy metabolism, and a validated target for therapeutic intervention in diabetes and obesity. Nevertheless, it is a challenging target for inhibitor development. Previously, we generated a recombinant antibody (scFv45) that recognizes selectively the oxidized, inactive conformation of PTP1B. Here, we provide a molecular basis for its interaction with reversibly oxidized PTP1B. Furthermore, we have identified a small molecule inhibitor that mimics the effects of scFv45. Our data provide proof-of-concept that stabilization of PTP1B in an inactive, oxidized conformation by small molecules can promote insulin and leptin signaling. This work illustrates a novel paradigm for inhibiting the signaling function of PTP1B that may be exploited for therapeutic intervention in diabetes and obesity.

  4. PTP1B Regulates Cortactin Tyrosine Phosphorylation by Targeting Tyr446*S⃞

    Science.gov (United States)

    Stuible, Matthew; Dubé, Nadia; Tremblay, Michel L.

    2008-01-01

    The emergence of protein-tyrosine phosphatase 1B (PTP1B) as a potential drug target for treatment of diabetes, obesity, and cancer underlies the importance of understanding its full range of cellular functions. Here, we have identified cortactin, a central regulator of actin cytoskeletal dynamics, as a substrate of PTP1B. A trapping mutant of PTP1B binds cortactin at the phosphorylation site Tyr446, the regulation and function of which have not previously been characterized. We show that phosphorylation of cortactin Tyr446 is induced by hyperosmolarity and potentiates apoptotic signaling during prolonged hyperosmotic stress. This study advances the importance of Tyr446 in the regulation of cortactin and provides a potential mechanism to explain the effects of PTP1B on processes including cell adhesion, migration, and tumorigenesis. PMID:18387954

  5. Low 5-HT1B receptor binding in the migraine brain

    DEFF Research Database (Denmark)

    Deen, Marie; Hansen, Hanne D; Hougaard, Anders

    2018-01-01

    Background The pathophysiology of migraine may involve dysfunction of serotonergic signaling. In particular, the 5-HT1B receptor is considered a key player due to the efficacy of 5-HT1B receptor agonists for treatment of migraine attacks. Aim To examine the cerebral 5-HT1B receptor binding....... Patients who reported migraine brain regions involved in pain modulation as regions of interest and applied a latent variable model (LVM) to assess the group effect on binding across these regions. Results Our data...... support a model wherein group status predicts the latent variable ( p = 0.038), with migraine patients having lower 5-HT1B receptor binding across regions compared to controls. Further, in a whole-brain voxel-based analysis, time since last migraine attack correlated positively with 5-HT1B receptor...

  6. F-spondin/spon1b expression patterns in developing and adult zebrafish.

    Directory of Open Access Journals (Sweden)

    Veronica Akle

    Full Text Available F-spondin, an extracellular matrix protein, is an important player in embryonic morphogenesis and CNS development, but its presence and role later in life remains largely unknown. We generated a transgenic zebrafish in which GFP is expressed under the control of the F-spondin (spon1b promoter, and used it in combination with complementary techniques to undertake a detailed characterization of the expression patterns of F-spondin in developing and adult brain and periphery. We found that F-spondin is often associated with structures forming long neuronal tracts, including retinal ganglion cells, the olfactory bulb, the habenula, and the nucleus of the medial longitudinal fasciculus (nMLF. F-spondin expression coincides with zones of adult neurogenesis and is abundant in CSF-contacting secretory neurons, especially those in the hypothalamus. Use of this new transgenic model also revealed F-spondin expression patterns in the peripheral CNS, notably in enteric neurons, and in peripheral tissues involved in active patterning or proliferation in adults, including the endoskeleton of zebrafish fins and the continuously regenerating pharyngeal teeth. Moreover, patterning of the regenerating caudal fin following fin amputation in adult zebrafish was associated with F-spondin expression in the blastema, a proliferative region critical for tissue reconstitution. Together, these findings suggest major roles for F-spondin in the CNS and periphery of the developing and adult vertebrate.

  7. E1B-55K mediated regulation of RNF4 STUbL promotes HAdV gene expression.

    Science.gov (United States)

    Müncheberg, Sarah; Hay, Ron T; Ip, Wing H; Meyer, Tina; Weiß, Christina; Brenke, Jara; Masser, Sawinee; Hadian, Kamyar; Dobner, Thomas; Schreiner, Sabrina

    2018-04-25

    HAdV E1B-55K is a multifunctional regulator of productive viral replication and oncogenic transformation in non-permissive mammalian cells. These functions depend on E1B-55K's posttranslational modification with the SUMO protein and its binding to HAdV E4orf6. Both early viral proteins recruit specific host factors to form an E3 Ubiquitin ligase complex that targets antiviral host substrates for proteasomal degradation. Recently, we reported that the PML-NB-associated factor Daxx represses efficient HAdV productive infection and is proteasomally degraded via a SUMO-E1B-55K-dependent, E4orf6-independent pathway, the details of which remained to be established.RNF4, a cellular SUMO-targeted Ubiquitin ligase (STUbL), induces ubiquitinylation of specific SUMOylated proteins and plays an essential role during DNA repair. Here, we show that E1B-55K recruits RNF4 to the insoluble nuclear matrix fraction of the infected cell to support RNF4/Daxx association, promoting Daxx PTM, and thus inhibiting this antiviral factor. Removing RNF4 from infected cells using RNAi resulted in blocking the proper establishment of viral replication centers and significantly diminished viral gene expression. These results provide a model for how HAdV antagonize the antiviral host responses by exploiting the functional capacity of cellular STUbLs. Thus, RNF4 and its STUbL function represent a positive factor during lytic infection and a novel candidate for future therapeutic antiviral intervention strategies. IMPORTANCE Daxx is a PML-NB-associated transcription factor, which was recently shown to repress efficient HAdV productive infection. To counteract this antiviral measurement during infection, Daxx is degraded via a novel pathway including viral E1B-55K and host proteasomes. This virus-mediated degradation is independent of the classical HAdV E3 Ubiquitin ligase complex, which is essential during viral infection to target other host antiviral substrates. To maintain productive viral life

  8. 20 CFR 655.700 - What statutory provisions govern the employment of H-1B, H-1B1, and E-3 nonimmigrants and how do...

    Science.gov (United States)

    2010-04-01

    ... Fashion Models, and Requirements for Employers Seeking To Employ Nonimmigrants on H-1b1 and E-3 Visas in... occupations or certain fashion models from any country, the INA, as amended, provides as follows: (1... work in a “specialty occupation” or as a fashion model of distinguished merit and ability in the United...

  9. Isolation and Characterization of Protein Tyrosine Phosphatase 1B (PTP1B Inhibitory Polyphenolic Compounds From Dodonaea viscosa and Their Kinetic Analysis

    Directory of Open Access Journals (Sweden)

    Zia Uddin

    2018-03-01

    Full Text Available Diabetes mellitus is one of a major worldwide concerns, regulated by either defects in secretion or action of insulin, or both. Insulin signaling down-regulation has been related with over activity of protein tyrosine phosphatase 1B (PTP1B enzyme, which has been a promising target for the treatment of diabetes mellitus. Herein, activity guided separation of methanol extract (95% of Dodonaea viscosa aerial parts afforded nine (1-9 polyphenolic compounds, all of them were identified through spectroscopic data including 2D NMR and HREIMS. Subsequently, their PTP1B inhibitory potentials were evaluated, in which all of the isolates exhibited significant dose-dependent inhibition with IC50 13.5–57.9 μM. Among them, viscosol (4 was found to be the most potent compound having IC50 13.5 μM. In order to unveil the mechanistic behavior, detailed kinetic study was carried out, in which compound 4 was observed as a reversible, and mixed type I inhibitor of PTP1B with inhibitory constant (Ki value of 4.6 μM. Furthermore, we annotated the major metabolites through HPLC-DAD-ESI/MS analysis, in which compounds 3, 6, 7, and 9 were found to be the most abundant metabolites in D. viscosa extract.

  10. Sulfone-stabilized carbanions for the reversible covalent capture of a posttranslationally-generated cysteine oxoform found in protein tyrosine phosphatase 1B (PTP1B).

    Science.gov (United States)

    Parsons, Zachary D; Ruddraraju, Kasi Viswanatharaju; Santo, Nicholas; Gates, Kent S

    2016-06-15

    Redox regulation of protein tyrosine phosphatase 1B (PTP1B) involves oxidative conversion of the active site cysteine thiolate into an electrophilic sulfenyl amide residue. Reduction of the sulfenyl amide by biological thiols regenerates the native cysteine residue. Here we explored fundamental chemical reactions that may enable covalent capture of the sulfenyl amide residue in oxidized PTP1B. Various sulfone-containing carbon acids were found to react readily with a model peptide sulfenyl amide via attack of the sulfonyl carbanion on the electrophilic sulfur center in the sulfenyl amide. Both the products and the rates of these reactions were characterized. The results suggest that capture of a peptide sulfenyl amide residue by sulfone-stabilized carbanions can slow, but not completely prevent, thiol-mediated generation of the corresponding cysteine-containing peptide. Sulfone-containing carbon acids may be useful components in the construction of agents that knock down PTP1B activity in cells via transient covalent capture of the sulfenyl amide oxoform generated during insulin signaling processes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Isolation and characterization of protein tyrosine phosphatase 1B (PTP1B) inhibitory polyphenolic compounds from Dodonaea viscosa and their kinetic analysis

    Science.gov (United States)

    Uddin, Zia; Song, Yeong Hun; Ullah, Mahboob; Li, Zuopeng; Kim, Jeong Yoon; Park, Ki Hun

    2018-03-01

    Diabetes mellitus is one of a major worldwide concerns, regulated by either defects in secretion or action of insulin, or both. Insulin signaling down-regulation has been related with over activity of protein tyrosine phosphatase 1B (PTP1B) enzyme, which has been a promising target for the treatment of diabetes mellitus. Herein, activity guided separation of methanol extract (95%) of Dodonaea viscosa aerial parts afforded nine (1-9) polyphenolic compounds, all of them were identified through spectroscopic data including 2D NMR and HREIMS. Subsequently, their PTP1B inhibitory potentials were evaluated, in which all of the isolates exhibited significant dose-dependent inhibition with IC50 13.5-57.9 μM. Among them, viscosol (4) was found to be the most potent compound having IC50 13.5 μM. In order to unveil the mechanistic behavior, detailed kinetic study was carried out, in which compound 4 was observed as a reversible, and mixed type I inhibitor of PTP1B with inhibitory constant (Ki) value of 4.6 μM. Furthermore, we annotated the major metabolites through HPLC-DAD-ESI/MS analysis, in which compounds 3, 6, 7 and 9 were found to be the most abundant metabolites in D.viscosa extract.

  12. Still Heart Encodes a Structural HMT, SMYD1b, with Chaperone-Like Function during Fast Muscle Sarcomere Assembly.

    Directory of Open Access Journals (Sweden)

    Kendal Prill

    Full Text Available The vertebrate sarcomere is a complex and highly organized contractile structure whose assembly and function requires the coordination of hundreds of proteins. Proteins require proper folding and incorporation into the sarcomere by assembly factors, and they must also be maintained and replaced due to the constant physical stress of muscle contraction. Zebrafish mutants affecting muscle assembly and maintenance have proven to be an ideal tool for identification and analysis of factors necessary for these processes. The still heart mutant was identified due to motility defects and a nonfunctional heart. The cognate gene for the mutant was shown to be smyd1b and the still heart mutation results in an early nonsense codon. SMYD1 mutants show a lack of heart looping and chamber definition due to a lack of expression of heart morphogenesis factors gata4, gata5 and hand2. On a cellular level, fast muscle fibers in homozygous mutants do not form mature sarcomeres due to the lack of fast muscle myosin incorporation by SMYD1b when sarcomeres are first being assembled (19hpf, supporting SMYD1b as an assembly protein during sarcomere formation.

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

    International Nuclear Information System (INIS)

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

    2004-01-01

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

  14. Liver-Specific Deletion of Protein-Tyrosine Phosphatase 1B (PTP1B) Improves Metabolic Syndrome and Attenuates Diet-Induced Endoplasmic Reticulum Stress

    Science.gov (United States)

    Delibegovic, Mirela; Zimmer, Derek; Kauffman, Caitlin; Rak, Kimberly; Hong, Eun-Gyoung; Cho, You-Ree; Kim, Jason K.; Kahn, Barbara B.; Neel, Benjamin G.; Bence, Kendra K.

    2009-01-01

    OBJECTIVE—The protein tyrosine phosphatase PTP1B is a negative regulator of insulin signaling; consequently, mice deficient in PTP1B are hypersensitive to insulin. Because PTP1B−/− mice have diminished fat stores, the extent to which PTP1B directly regulates glucose homeostasis is unclear. Previously, we showed that brain-specific PTP1B−/− mice are protected against high-fat diet–induced obesity and glucose intolerance, whereas muscle-specific PTP1B−/− mice have increased insulin sensitivity independent of changes in adiposity. Here we studied the role of liver PTP1B in glucose homeostasis and lipid metabolism. RESEARCH DESIGN AND METHODS—We analyzed body mass/adiposity, insulin sensitivity, glucose tolerance, and lipid metabolism in liver-specific PTP1B−/− and PTP1Bfl/fl control mice, fed a chow or high-fat diet. RESULTS—Compared with normal littermates, liver-specific PTP1B−/− mice exhibit improved glucose homeostasis and lipid profiles, independent of changes in adiposity. Liver-specific PTP1B−/− mice have increased hepatic insulin signaling, decreased expression of gluconeogenic genes PEPCK and G-6-Pase, enhanced insulin-induced suppression of hepatic glucose production, and improved glucose tolerance. Liver-specific PTP1B−/− mice exhibit decreased triglyceride and cholesterol levels and diminished expression of lipogenic genes SREBPs, FAS, and ACC. Liver-specific PTP1B deletion also protects against high-fat diet–induced endoplasmic reticulum stress response in vivo, as evidenced by decreased phosphorylation of p38MAPK, JNK, PERK, and eIF2α and lower expression of the transcription factors C/EBP homologous protein and spliced X box-binding protein 1. CONCLUSIONS—Liver PTP1B plays an important role in glucose and lipid metabolism, independent of alterations in adiposity. Inhibition of PTP1B in peripheral tissues may be useful for the treatment of metabolic syndrome and reduction of cardiovascular risk in addition to

  15. Inhibition of protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase by xanthones from Cratoxylum cochinchinense, and their kinetic characterization.

    Science.gov (United States)

    Li, Zuo Peng; Song, Yeong Hun; Uddin, Zia; Wang, Yan; Park, Ki Hun

    2018-02-01

    Cratoxylum cochinchinense displayed significant inhibition against protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase, both of which are key target enzymes to attenuate diabetes and obesity. The compounds responsible for both enzymes inhibition were identified as twelve xanthones (1-12) among which compounds 1 and 2 were found to be new ones. All of them simultaneously inhibited PTP1B with IC 50 s of (2.4-52.5 µM), and α-glucosidase with IC 50 values of (1.7-72.7 µM), respectively. Cratoxanthone A (3) and γ-mangostin (7) were estimated to be most active inhibitors against both PTP1B (IC 50  = 2.4 µM for 3, 2.8 µM for 7) and α-glucosidase (IC 50  = 4.8 µM for 3, 1.7 µM for 7). In kinetic studies, all isolated xanthones emerged to be mixed inhibitors of α-glucosidase, whereas they behaved as competitive inhibitors of PTP1B. In time dependent experiments, compound 3 showed isomerization inhibitory behavior with following kinetic parameters: K i app  = 2.4 µM; k 5  = 0.05001 µM -1  S -1 and k 6  = 0.02076 µM -1  S -1 . Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Pineal-mediated inhibition of prolactin cell activity: Investigation of dopaminergic involvement

    International Nuclear Information System (INIS)

    Burns, D.M.

    1989-01-01

    The present studies in the male Syrian hamster addressed two issues. First, it was of interest to determine if anterior pituitaries of long photoperiod-exposed male hamsters possess dopamine receptors, which are presumably necessary for responsiveness to dopamine. This was accomplished by analysis of 3 H-spiperone binding to anterior pituitary membranes. Second, possible changes in pituitary sensitivity to dopamine were assessed by comparison of dose response curves for the inhibition by dopamine of prolactin release from hemipituitaries incubated in vitro from both long and short photoperiod-exposed animals over a series of time points from three to fifteen weeks. In the second series of experiments, adult female F344 rats received daily injection of melatonin or saline vehicle. After two weeks, half of the animals were sacrificed for analysis of 3 H-spiperone binding to anterior pituitary membranes, measurement of hypothalamic dopamine turnover and analysis of in vitro pituitary sensitivity to dopamine. The remaining animals received subcutaneous implants containing DES and injections were continued on the same schedule until sacrifice four weeks later for measurement of the same parameters

  17. Growth hormone and prolactin in Andrias davidianus: cDNA cloning, tissue distribution and phylogenetic analysis.

    Science.gov (United States)

    Yang, Liping; Meng, Zining; Liu, Yun; Zhang, Yong; Liu, Xiaochun; Lu, Danqi; Huang, Junhai; Lin, Haoran

    2010-01-15

    The Chinese giant salamander (Andrias davidianus) is one of the largest and 'living fossil' species of amphibian. To obtain genetic information for this species, the cDNAs encoding growth hormone (adGH) and prolactin (adPRL) were cloned from a pituitary cDNA library. The isolated adGH cDNA consisted of 864 bp and encoded a propeptide of 215 amino acids, while the cDNA of adPRL was 1106 bp in length and encoded a putative peptide of 229 amino acids. Expression of the GH and PRL mRNA was only detected in the pituitary. Phylogenetic analyses were performed based on the isolated pituitary hormone sequences using maximum parsimony and neighbor-joining algorithms. The clustering results are similar to that based on the morphological characteristics or the rRNA genes, which indicate that the two orders (Anura and Caudata) of amphibian were monophyletic, and that A. davidianus was diverged early in the Caudate clade. These results indicated that both the GH and PRL sequence might be useful to study the phylogenies of relatively moderate evolved groups.

  18. Oxytocin and prolactin release after hypertonic saline administration in melatonin-treated male Syrian hamsters

    Energy Technology Data Exchange (ETDEWEB)

    Juszczak, M.; Steger, R.W.; Fadden, C.; Bartke, A. [Southern Illinois Univ., Carbondale, IL (United States)

    1996-12-31

    The aim of the present investigations was to examine the effects of melatonin (Mel) on oxytocin (OT) release under conditions of osmotic stimulation, brought about by hypertonic saline administration, as well as to determine whether osmotically stimulated OT release in Mel-treated Syrian hamster is associated with alterations in the release of prolactin (PRL) and in norepinephrine (NE) and dopamine (DA) content in the hypothalamus. In both Mel- and vehicle-treated hamsters, injection of hypertonic saline was followed by a significant decrease in OT content in the pituitary neurointermediate lobe (NIL) and elevation of plasma OT and PRL levels. Melatonin injections had no significant affect on NIL OT content in either isotonic- or hypertonic-saline treated animals. Pretreatment with Mel did not alter plasma OT or PRL levels in isotonic saline-injected animals. However, Mel facilitated the release of OT, but prevented the release of PRL after hypertonic saline administration. Melatonin treatment reduced hypothalamic NE content (but not that of DA) in isotonic-saline treated animals. After osmotic stimulation, hypothalamic content of NE and DA was significantly lower in Mel-treated than in vehicle-treated animals. Data from the present study suggest that the osmotically-stimulated release of OT and PRL seems to be related to the activation of noradrenergic rather than dopaminergic transmission. Both dopaminergic and noradrenergic transmission may be, however, involved in mediating the effects of Mel on the osmotically-activated OT and PRL release. (author). 48 refs, 3 figs.

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

    International Nuclear Information System (INIS)

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

    1984-01-01

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

  20. [Metabolism of thyroid gland cells as affected by prolactin and emotional-physical stress].

    Science.gov (United States)

    Strizhkov, V V

    1991-01-01

    A study was made of the role of prolactin (PRL) in the regulation of thyroid function in intact animals and in those exposed to stress (swimming was used as physical exercise). A single daily dose of 125 micrograms of PRL per 100 g of body mass was injected subcutaneously in 0.5 ml of saline solution during a week to male rats (control: intact rats; injection of 0.5 ml of saline solution subcutaneously). Redox enzymes; succinate dehydrogenase, lactate dehydrogenase, glucose-6-phosphate dehydrogenase, NAD.H2 and NADP.H2, ATPase and monoamine oxidase, total protein, RNA and glycogen in glandular cells were investigated histochemically 24 h after the last injection of PRL or saline, 30 min., 1, 2, 3, 5 and 7 hours after swimming or right after complete fatigue (in the presence of experimental hyperprolactinemia). A conclusion has been made that one of the most important mechanisms of the adaptive effect of PRL is its ability to suppress thyroid function, thus decreasing the metabolism level, which results in reduction of oxygen consumption and improves body tolerance to stress.

  1. Prolactin response to thyrotropin-releasing hormone in early and advanced human breast cancer

    International Nuclear Information System (INIS)

    Barni, S.; Lissoni, P.; Tancini, G.

    1986-01-01

    While prolactin (PRL) has been shown to stimulate the development of mammary carcinoma in several animal species, its role in human breast cancer remains to be established. To further investigate PRL secretion in human breast cancer, its basal levels and response to thyrotropin-releasing hormone (TRH) were evaluated in 16 patients (6 with no metastases and 10 with metastatic locations). The control group consisted of 19 healthy women. High PRL basal concentrations were seen in 2 patients only; no significant differences were found between the other patients and the normal subjects. The PRL increase induced by TRH administration was significantly higher in patients than in controls. Finally a change in the hormonal secretion was found after chemotherapy in 3 of the 5 patients in whom PRL response to TRH was evaluated either before or 10-12 days after a cycle of intravenous CMF adjuvant chemotherapy. These results demostrate the existence of an exaggerated response of PRL to TRH in patients with breast cancer, even in the presence of normal basal levels. Moreover, they would seem to suggest a possible influence of CMF on PRL response to TRH stimulation

  2. Protective Effect of Prolactin against Methylmercury-Induced Mutagenicity and Cytotoxicity on Human Lymphocytes

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    Liz Carmem Silva-Pereira

    2014-09-01

    Full Text Available Mercury exhibits cytotoxic and mutagenic properties as a result of its effect on tubulin. This toxicity mechanism is related to the production of free radicals that can cause DNA damage. Methylmercury (MeHg is one of the most toxic of the mercury compounds. It accumulates in the aquatic food chain, eventually reaching the human diet. Several studies have demonstrated that prolactin (PRL may be differently affected by inorganic and organic mercury based on interference with various neurotransmitters involved in the regulation of PRL secretion. This study evaluated the cytoprotective effect of PRL on human lymphocytes exposed to MeHg in vitro, including observation of the kinetics of HL-60 cells (an acute myeloid leukemia lineage treated with MeHg and PRL at different concentrations, with both treatments with the individual compounds and combined treatments. All treatments with MeHg produced a significant increase in the frequency of chromatid gaps, however, no significant difference was observed in the chromosomal breaks with any treatment. A dose-dependent increase in the mitotic index was observed for treatments with PRL, which also acts as a co-mitogenic factor, regulating proliferation by modulating the expression of genes that are essential for cell cycle progression and cytoskeleton organization. These properties contribute to the protective action of PRL against the cytotoxic and mutagenic effects of MeHg.

  3. Bovine serum prolactin, growth hormone, and triiodothyronine levels during late pregnancy and early lactation

    International Nuclear Information System (INIS)

    Johke, Tetsu; Hodate, Kouichi

    1977-01-01

    Changes of serum prolactin (PRL), growth hormone (GH), and triiodothyronine (T3) levels in Holstein dairy cows during late pregnancy and early lactation were determined by radioimmunoassays. The cows calved in September. Mean serum PRL ranged 9.9 ng/ml to 12.4 ng/ml during the 3rd to 7th day prepartum. It increased to a peak value of 87.3 ng/ml on the day of parturition from 57.5 ng/ml on the day before calving, and decreased to 13.9 ng/ml within 3 days postpartum. During the 2nd to 30th day prepartum, serum GH varied between 2.4 and 4.0 ng/ml and increased to 8.0 ng/ml on the day of calving. During a week postpartum, serum GH ranged from 5.2 to 8.2 ng/ml. Mean serum GH during a week postpartum was higher than that of prepartum (P < 0.001). Mean serum T3 level during 5 days prepartum varied 104.2 to 108.8 ng/dl and decreased to 93 ng/dl on the day of calving. During 5 days postpartum, mean T3 level varied 73.0 to 83.8 ng/dl. Contrary to GH, mean serum T3 level during 5 day postpartum was significantly lower than that of prepartum (P < 0.001). (auth.)

  4. Protective Effect of Prolactin against Methylmercury-Induced Mutagenicity and Cytotoxicity on Human Lymphocytes

    Science.gov (United States)

    Silva-Pereira, Liz Carmem; da Rocha, Carlos Alberto Machado; Cunha, Luiz Raimundo Campos da Silva e; da Costa, Edmar Tavares; Guimarães, Ana Paula Araújo; Pontes, Thais Brilhante; Diniz, Domingos Luiz Wanderley Picanço; Leal, Mariana Ferreira; Moreira-Nunes, Caroline Aquino; Burbano, Rommel Rodríguez

    2014-01-01

    Mercury exhibits cytotoxic and mutagenic properties as a result of its effect on tubulin. This toxicity mechanism is related to the production of free radicals that can cause DNA damage. Methylmercury (MeHg) is one of the most toxic of the mercury compounds. It accumulates in the aquatic food chain, eventually reaching the human diet. Several studies have demonstrated that prolactin (PRL) may be differently affected by inorganic and organic mercury based on interference with various neurotransmitters involved in the regulation of PRL secretion. This study evaluated the cytoprotective effect of PRL on human lymphocytes exposed to MeHg in vitro, including observation of the kinetics of HL-60 cells (an acute myeloid leukemia lineage) treated with MeHg and PRL at different concentrations, with both treatments with the individual compounds and combined treatments. All treatments with MeHg produced a significant increase in the frequency of chromatid gaps, however, no significant difference was observed in the chromosomal breaks with any treatment. A dose-dependent increase in the mitotic index was observed for treatments with PRL, which also acts as a co-mitogenic factor, regulating proliferation by modulating the expression of genes that are essential for cell cycle progression and cytoskeleton organization. These properties contribute to the protective action of PRL against the cytotoxic and mutagenic effects of MeHg. PMID:25247425

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

    International Nuclear Information System (INIS)

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

    1984-01-01

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

  6. Oxytocin and prolactin release after hypertonic saline administration in melatonin-treated male Syrian hamsters

    International Nuclear Information System (INIS)

    Juszczak, M.; Steger, R.W.; Fadden, C.; Bartke, A.

    1996-01-01

    The aim of the present investigations was to examine the effects of melatonin (Mel) on oxytocin (OT) release under conditions of osmotic stimulation, brought about by hypertonic saline administration, as well as to determine whether osmotically stimulated OT release in Mel-treated Syrian hamster is associated with alterations in the release of prolactin (PRL) and in norepinephrine (NE) and dopamine (DA) content in the hypothalamus. In both Mel- and vehicle-treated hamsters, injection of hypertonic saline was followed by a significant decrease in OT content in the pituitary neurointermediate lobe (NIL) and elevation of plasma OT and PRL levels. Melatonin injections had no significant affect on NIL OT content in either isotonic- or hypertonic-saline treated animals. Pretreatment with Mel did not alter plasma OT or PRL levels in isotonic saline-injected animals. However, Mel facilitated the release of OT, but prevented the release of PRL after hypertonic saline administration. Melatonin treatment reduced hypothalamic NE content (but not that of DA) in isotonic-saline treated animals. After osmotic stimulation, hypothalamic content of NE and DA was significantly lower in Mel-treated than in vehicle-treated animals. Data from the present study suggest that the osmotically-stimulated release of OT and PRL seems to be related to the activation of noradrenergic rather than dopaminergic transmission. Both dopaminergic and noradrenergic transmission may be, however, involved in mediating the effects of Mel on the osmotically-activated OT and PRL release. (author). 48 refs, 3 figs

  7. Enhancement of Human Prolactin Synthesis by Sodium Butyrate Addition to Serum-Free CHO Cell Culture

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    Herbert Rodrigues Goulart

    2010-01-01

    Full Text Available Sodium butyrate (NaBu has been used as a productivity enhancer for the synthesis of recombinant proteins in Chinese hamster ovary (CHO cells. Thus, the influence of NaBu on the production of recombinant human prolactin (hPRL from CHO cells was investigated for the first time. CHO cell cultures were submitted to a treatment with different concentrations of NaBu (0.25 to 4 mM. Quantitative and qualitative analyses by reverse-phase high-performance liquid chromatography (RP-HPLC and Western blot or SDS-PAGE, carried out directly on CHO-conditioned medium, showed that the highest hPRL expression was obtained with 1 mM NaBu. In vitro biological assays based on noble rat lymphoma (Nb2 and mouse pro-B lymphoma (Ba/F3-LLP cells were carried out on purified hPRL. Its bioactivity in the presence of NaBu was not apparently different from that of the First International Reference Reagent of recombinant hPRL (WHO 97/714. Our results show that NaBu increased the synthesis of recombinant hPRL in CHO cells, apparently without compromising either its structure or function.

  8. Growth hormone and prolactin responses during partial and whole body warm-water immersions.

    Science.gov (United States)

    Koska, J; Rovensky, J; Zimanova, T; Vigas, M

    2003-05-01

    To elucidate the role of core and skin thermoreceptors in the release of growth hormone (GH) and prolactin (PRL), a sequence of two experiments using whole-body (head-out) and partial (one forearm) hot water immersions was performed. Experiment 1: Nine healthy men were exposed to head-out and partial water immersions (25 min, 38-39 degrees C). Head-out immersion increased the core temperature (38.0 +/- 0.1 vs. 36.7 +/- 0.1 degrees C, P immersion the core temperature was slightly elevated (36.8 +/- 0.1 vs. 36.6 +/- 0.1, P immersed one forearm once in 39 degrees C and once in 38 degrees C water. The measurements were performed in 5-min intervals. The GH concentration increased gradually from the beginning of the immersions (min 10; 39 degrees C: 1.9 +/- 1.0 vs. 0.6 +/- 0.3 ng mL(-1), P Immersion in 38 degrees C water did not induce core temperature changes. Peripheral thermoreceptors are involved in GH release when the body is exposed to elevated environmental temperature while a substantial elevation of core temperature is a precondition of PRL release.

  9. Relationship between local cerebral glucose uptakes, serum prolactin, growth hormone and cortisol levels changes during epilepsy

    International Nuclear Information System (INIS)

    Wang Mingfang; Mao Xianghui; Tang Ganghua; Zhao Jun; Sun Aijun

    2002-01-01

    Objective: To explore the relation of local cerebral FDG uptake value of glucose to the changes of prolactin (PRL), growth hormone (GH) and cortisol levels in serum during epilepsy. Methods: 76 epileptic patients with solitary epileptic focus were examined by 2-deoxy-2-[ 18 F] fluoro-D-glucose ( 18 F-FDG) positron emission tomography (PET) imaging and the FDG uptake value of epileptic foci were measured. Serum PRL, GH and cortisol levels of the patients were determined by radioimmunoassay (RIA) before and after seizures. Results: During ictal studies, all patients showed increased FDG uptake of epileptic foci compared with that in interictal phase. The serum PRL, GH and cortisol levels were significant higher after seizures. The changes of hormone levels correlated significantly with the lengths of seizure free intervals (SFIs) and with the types of seizures. But the variations of hormone levels had no relation with the site and FDG uptake of epileptic foci. In patients with absentia seizures, no significant increase was observed in serum PRL and cortisol levels. The changes of GH were not related with the types of seizures. Also, it was found that changes of hormone levels had significant relations to the lengths of SFIs. Conclusions: Serum PRL, GH and cortisol levels were significantly different before and after seizures. This study suggests that changes of postictal hormone levels correlated significantly with the types of seizures and lengths of SFIs, but the changes of hormone levels are not related with the site and FDG uptake of epileptic foci

  10. High Prolactin Excretion in Patients with Diabetes Mellitus and Impaired Renal Function.

    Science.gov (United States)

    Triebel, Jakob; Moreno-Vega, Aura Ileana; Vázquez-Membrillo, Miguel; Nava, Gabriel; García-Franco, Renata; López-Star, Ellery; Baldivieso-Hurtado, Olivia; Ochoa, Daniel; Macotela, Yazmín; Bertsch, Thomas; Martinez de la Escalera, Gonzalo; Clapp, Carmen

    2015-01-01

    The metabolic clearance of prolactin (PRL) is partially executed by the kidney. Here, we investigate the urine excretion of PRL in patients with Diabetes Mellitus and renal impairment. Serum and urine samples were collected from male, mestizo patients in central Mexico employing a cross-sectional study design. Ninety-eight individuals had either no diabetes and normal renal function (control), diabetes and normal renal function, or diabetes with impaired renal function. PRL was determined by a chemiluminescent immunometric assay; protein, albumin, and creatinine were evaluated using quantitative colorimetric assays. The results were analyzed using ANOVA-testing. Patients with Diabetes Mellitus and renal impairment had significantly higher urine PRL levels than patients with Diabetes Mellitus and normal renal function and control patients. Higher urine PRL levels were associated with lower glomerular filtration rates, higher serum creatinine, and higher urinary albumin-to-creatinine ratios (UACR). Urine PRL levels correlated positively with UACR. Serum PRL levels were similar among groups. Patients with Diabetes Mellitus and impaired renal function demonstrate a high urinary PRL excretion. Urinary PRL excretion in the context of proteinuria could contribute to PRL dysregulation in renal impairment.

  11. Prolactin Alters the Mammary Epithelial Hierarchy, Increasing Progenitors and Facilitating Ovarian Steroid Action.

    Science.gov (United States)

    O'Leary, Kathleen A; Shea, Michael P; Salituro, Stephanie; Blohm, Courtney E; Schuler, Linda A

    2017-10-10

    Hormones drive mammary development and function and play critical roles in breast cancer. Epidemiologic studies link prolactin (PRL) to increased risk for aggressive cancers that express estrogen receptor α (ERα). However, in contrast to ovarian steroids, PRL actions on the mammary gland outside of pregnancy are poorly understood. We employed the transgenic NRL-PRL model to examine the effects of PRL alone and with defined estrogen/progesterone exposure on stem/progenitor activity and regulatory networks that drive epithelial differentiation. PRL increased progenitors and modulated transcriptional programs, even without ovarian steroids, and with steroids further raised stem cell activity associated with elevated canonical Wnt signaling. However, despite facilitating some steroid actions, PRL opposed steroid-driven luminal maturation and increased CD61 + luminal cells. Our findings demonstrate that PRL can powerfully influence the epithelial hierarchy alone and temper the actions of ovarian steroids, which may underlie its role in the development of breast cancer. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  12. Increased serum level of prolactin is related to autoantibody production in systemic lupus erythematosus.

    Science.gov (United States)

    Yang, J; Li, Q; Yang, X; Li, M

    2016-04-01

    Prolactin (PRL) is known to aid effector B cells and augment autoimmunity, but the role of PRL in systemic lupus erythematosus (SLE) is not fully elucidated. The aim of this study was to determine the correlation between the serum levels of PRL and autoantibody production in SLE. Blood levels of PRL, anti-double-stranded DNA (ds-DNA) antibody, immunoglobulin M (IgM) and immunoglobulin G (IgG) were determined in samples from 30 adult patients with SLE and 25 healthy controls. The relationships between the serum level of PRL and SLE disease activity, as well as the titres of the ds-DNA antibody, IgM and IgG were determined. The serum level of PRL was higher in the SLE patients than in the healthy controls. PRL concentration increased during SLE flares-ups and decreased following disease remission. There was a positive correlation between the PRL concentration and serum levels of IgM, IgG and ds-DNA antibody titre. These data suggest that the serum level of PRL was closely related to the antibody production and disease activity of SLE patients. PRL concentration was dramatically reduced upon the remission of disease activity, indicating that PRL levels might be a promising predictor of SLE disease severity. © The Author(s) 2015.

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

    Science.gov (United States)

    Overgaard, Martin; Pedersen, Susanne Møller

    2017-10-26

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

  14. Alcohol binding in the C1 (C1A + C1B) domain of protein kinase C epsilon

    Science.gov (United States)

    Pany, Satyabrata; Das, Joydip

    2015-01-01

    Background Alcohol regulates the expression and function of protein kinase C epsilon (PKCε). In a previous study we identified an alcohol binding site in the C1B, one of the twin C1 subdomains of PKCε. Methods In this study, we investigated alcohol binding in the entire C1 domain (combined C1A and C1B) of PKCε. Fluorescent phorbol ester, SAPD and fluorescent diacylglycerol (DAG) analog, dansyl-DAG were used to study the effect of ethanol, butanol, and octanol on the ligand binding using fluorescence resonance energy transfer (FRET). To identify alcohol binding site(s), PKCεC1 was photolabeled with 3-azibutanol and 3-azioctanol, and analyzed by mass spectrometry. The effects of alcohols and the azialcohols on PKCε were studied in NG108-15 cells. Results In the presence of alcohol, SAPD and dansyl-DAG showed different extent of FRET, indicating differential effects of alcohol on the C1A and C1B subdomains. Effects of alcohols and azialcohols on PKCε in NG108-15 cells were comparable. Azialcohols labeled Tyr-176 of C1A and Tyr-250 of C1B. Inspection of the model structure of PKCεC1 reveals that these residues are 40 Å apart from each other indicating that these residues form two different alcohol binding sites. Conclusions The present results provide evidence for the presence of multiple alcohol-binding sites on PKCε and underscore the importance of targeting this PKC isoform in developing alcohol antagonists. PMID:26210390

  15. A novel microduplication of ARID1B: Clinical, genetic, and proteomic findings.

    Science.gov (United States)

    Seabra, Catarina M; Szoko, Nicholas; Erdin, Serkan; Ragavendran, Ashok; Stortchevoi, Alexei; Maciel, Patrícia; Lundberg, Kathleen; Schlatzer, Daniela; Smith, Janice; Talkowski, Michael E; Gusella, James F; Natowicz, Marvin R

    2017-09-01

    Genetic alterations of ARID1B have been recently recognized as one of the most common mendelian causes of intellectual disability and are associated with both syndromic and non-syndromic phenotypes. The ARID1B protein, a subunit of the chromatin remodeling complex SWI/SNF-A, is involved in the regulation of transcription and multiple downstream cellular processes. We report here the clinical, genetic, and proteomic phenotypes of an individual with a unique apparent de novo mutation of ARID1B due to an intragenic duplication. His neurodevelopmental phenotype includes a severe speech/language disorder with full scale IQ scores 78-98 and scattered academic skill levels, expanding the phenotypic spectrum of ARID1B mutations. Haploinsufficiency of ARID1B was determined both by RNA sequencing and quantitative RT-PCR. Fluorescence in situ hybridization analysis supported an intragenic localization of the ARID1B copy number gain. Principal component analysis revealed marked differentiation of the subject's lymphoblast proteome from that of controls. Of 3426 proteins quantified, 1014 were significantly up- or down-regulated compared to controls (q constitutional haploinsufficiency of ARID1B causes syndromic and non-syndromic developmental disabilities. © 2017 Wiley Periodicals, Inc.

  16. The Role of PTP1B O-GlcNAcylation in Hepatic Insulin Resistance

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    Yun Zhao

    2015-09-01

    Full Text Available Protein tyrosine phosphatase 1B (PTP1B, which can directly dephosphorylate both the insulin receptor and insulin receptor substrate 1 (IRS-1, thereby terminating insulin signaling, reportedly plays an important role in insulin resistance. Accumulating evidence has demonstrated that O-GlcNAc modification regulates functions of several important components of insulin signal pathway. In this study, we identified that PTP1B is modified by O-GlcNAcylation at three O-GlcNAc sites (Ser104, Ser201, and Ser386. Palmitate acid (PA impaired the insulin signaling, indicated by decreased phosphorylation of both serine/threonine-protein kinase B (Akt and glycogen synthase kinase 3 beta (GSK3β following insulin administration, and upregulated PTP1B O-GlcNAcylation in HepG2 cells. Compared with the wild-type, intervention PTP1B O-GlcNAcylation by site-directed gene mutation inhibited PTP1B phosphatase activity, resulted in a higher level of phosphorylated Akt and GSK3β, recovered insulin sensitivity, and improved lipid deposition in HepG2 cells. Taken together, our research showed that O-GlcNAcylation of PTP1B can influence insulin signal transduction by modulating its own phosphatase activity, which participates in the process of hepatic insulin resistance.

  17. Review of interferon beta-1b in the treatment of early and relapsing multiple sclerosis

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    Damiano Paolicelli

    2009-07-01

    Full Text Available Damiano Paolicelli, Vita Direnzo, Maria TrojanoDepartment of Neurological and Psychiatric Sciences, University of Bari, Bari, ItalyAbstract: Multiple sclerosis (MS is the most common autoimmune illness of the central nervous system. For many years the inflammatory manifestations of MS were treated using only corticosteroids. Since the 1990s the results of several clinical trials with immunomodulatory agents have changed the therapeutic approach to this disease. Interferon beta (IFNβ-1b represents the pioneer of those therapies. There is growing evidence from clinical trials on relapsing-remitting MS and clinically isolated syndromes suggestive of MS that IFNβ-1b reduces the frequency and severity of relapses and the development of new and active brain lesions as assessed by magnetic resonance imaging. Long-term data suggest a persistent efficacy of IFNβ-1b on disease activity and a positive effect in slowing disability worsening. Furthermore a reduction of relapse rate and a slight positive effect on the progression were demonstrated when IFNβ-1b was administered to still-active secondary progressive MS. IFNβ-1b therapy is well tolerated and relatively free of long-term side effects. In spite of the emergence of new agents for the treatment of MS, IFNβ-1b still remains a first-line therapy with a fundamental role in all stages of the disease.Keywords: interferon beta-1b, relapsing-remitting multiple sclerosis, clinically isolated syndromes, efficacy, safety, neutralizing antibodies

  18. Hypotonic stimuli enhance proton-gated currents of acid-sensing ion channel-1b

    International Nuclear Information System (INIS)

    Ugawa, Shinya; Ishida, Yusuke; Ueda, Takashi; Yu, Yong; Shimada, Shoichi

    2008-01-01

    Acid-sensing ion channels (ASICs) are strong candidates for mammalian mechanoreceptors. We investigated whether mouse acid-sensing ion channel-1b (ASIC1b) is sensitive to mechanical stimuli using oocyte electrophysiology, because ASIC1b is located in the mechanosensory stereocilia of cochlear hair cells. Hypotonic stimuli that induced membrane stretch of oocytes evoked no significant current in ASIC1b-expressing oocytes at pH 7.5. However, acid (pH 4.0 or 5.0)-evoked currents in the oocytes were substantially enhanced by the hypotonicity, showing mechanosensitivity of ASIC1b and possible mechanogating of the channel in the presence of other components. Interestingly, the ASIC1b channel was permeable to K + (a principal charge carrier for cochlear sensory transduction) and the affinity of the channel for amiloride (IC 50 (inhibition constant) = approximately 48.3 μM) was quite similar to that described for the mouse hair cell mechanotransducer current. Taken together, these data raise the possibility that ASIC1b participates in cochlear mechanoelectrical transduction

  19. Discovery and study of novel protein tyrosine phosphatase 1B inhibitors

    Science.gov (United States)

    Zhang, Qian; Chen, Xi; Feng, Changgen

    2017-10-01

    Protein tyrosine phosphatase 1B (PTP1B) is considered to be a target for therapy of type II diabetes and obesity. So it is of great significance to take advantage of a computer aided drug design protocol involving the structured-based virtual screening with docking simulations for fast searching small molecule PTP1B inhibitors. Based on optimized complex structure of PTP1B bound with specific inhibitor of IX1, structured-based virtual screening against a library of natural products containing 35308 molecules, which was constructed based on Traditional Chinese Medicine database@ Taiwan (TCM database@ Taiwan), was conducted to determine the occurrence of PTP1B inhibitors using the Lubbock module and CDOCKER module from Discovery Studio 3.1 software package. The results were further filtered by predictive ADME simulation and predictive toxic simulation. As a result, 2 good drug-like molecules, namely para-benzoquinone compound 1 and Clavepictine analogue 2 were identified ultimately with the dock score of original inhibitor (IX1) and the receptor as a threshold. Binding model analyses revealed that these two candidate compounds have good interactions with PTP1B. The PTP1B inhibitory activity of compound 2 hasn't been reported before. The optimized compound 2 has higher scores and deserves further study.

  20. Rrp1b, a new candidate susceptibility gene for breast cancer progression and metastasis.

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    Nigel P S Crawford

    2007-11-01

    Full Text Available A novel candidate metastasis modifier, ribosomal RNA processing 1 homolog B (Rrp1b, was identified through two independent approaches. First, yeast two-hybrid, immunoprecipitation, and functional assays demonstrated a physical and functional interaction between Rrp1b and the previous identified metastasis modifier Sipa1. In parallel, using mouse and human metastasis gene expression data it was observed that extracellular matrix (ECM genes are common components of metastasis predictive signatures, suggesting that ECM genes are either important markers or causal factors in metastasis. To investigate the relationship between ECM genes and poor prognosis in breast cancer, expression quantitative trait locus analysis of polyoma middle-T transgene-induced mammary tumor was performed. ECM gene expression was found to be consistently associated with Rrp1b expression. In vitro expression of Rrp1b significantly altered ECM gene expression, tumor growth, and dissemination in metastasis assays. Furthermore, a gene signature induced by ectopic expression of Rrp1b in tumor cells predicted survival in a human breast cancer gene expression dataset. Finally, constitutional polymorphism within RRP1B was found to be significantly associated with tumor progression in two independent breast cancer cohorts. These data suggest that RRP1B may be a novel susceptibility gene for breast cancer progression and metastasis.

  1. Contribution of CYP1B1 mutations and founder effect to primary congenital glaucoma in Mexico.

    Science.gov (United States)

    Zenteno, Juan Carlos; Hernandez-Merino, Elena; Mejia-Lopez, Herlinda; Matías-Florentino, Margarita; Michel, Norma; Elizondo-Olascoaga, Celia; Korder-Ortega, Vincent; Casab-Rueda, Homero; Garcia-Ortiz, Jose Elias

    2008-01-01

    The frequency of primary congenital glaucoma (PCG)-causing CYP1B1 mutations varies importantly among distinct populations, ranging from 20% in Indonesians and Japanese to about 100% among the Saudi Arabians and Slovakian Gypsies. Thus, the molecular characterization of large groups of PCG from different ethnic backgrounds is important to establish the actual CYP1B1 contribution in specific populations. In this work, the molecular analysis of the CYP1B1 gene in a group of Mexican PCG patients is reported. Thirty unrelated Mexican patients fulfilling the clinical criteria for PCG were included. Two cases were familial and with proven consanguinity, originating from distinct regions of the country. Polymerase chain reaction amplification and direct automated sequencing of the CYP1B1 coding region was performed in each participating subject. An identical pathogenic CYP1B1 mutation was demonstrated in 2 unrelated PCG subjects. The mutation consisted of a homozygous G to A transition at nucleotide position 1505 in exon 3, which predicted a substitution of glutamic acid for lysine at residue 387 of the protein (E387K). In the remaining 28 PCG subjects, no deleterious mutations were identified. Both subjects with the E387K mutation shared a same haplotype for 5 CYP1B1 intragenic single nucleotide polymorphisms, indicating a common origin of the allele. Mexican patients with PCG are rarely (less than 10%) due to CYP1B1 mutations. Available data indicate that most of the non-Brazilian Latin American PCG patients investigated to date are not due to CYP1B1 defects. Populations with low incidence of CYP1B1 mutations are appropriate candidates for the identification of novel PCG-causing genes.

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

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    Kosuke Matsuo

    2011-01-01

    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.

  3. Aldo-keto Reductase Family 1 B10 as a Novel Target for Breast Cancer Treatment

    Science.gov (United States)

    2010-08-01

    overexpressed in tested human breast cancer tissues and mediates acetyl-CoA carboxylase-α ( ACCA ) stability, affecting fatty acid de novo synthesis and...9703; Fax. 217-545-3227; E-mail: dcao@siumed.edu Running title: AKR1B10 as a new risk factor for breast cancer Abbreviations used: ACCA , acetyl...The effect of AKR1B10 expression in cancer tissue on patient survival was evaluated with Kaplan - Meier plots, and results showed that AKR1B10

  4. CYP1B1 Mutations in Individuals With Primary Congenital Glaucoma and Residing in Denmark

    DEFF Research Database (Denmark)

    Grønskov, Karen; Redó-Riveiro, Alba; Sandfeld, Lisbeth

    2016-01-01

    Primary congenital glaucoma (PCG OMIM 231300) can be caused by pathogenic sequence variations in cytochrome P450, subfamily 1, polypeptide 1 (CYP1B1). The purpose of this study was to investigate the contribution of sequence variations in CYP1B1 in a cohort of individuals with PCG residing...... mutations, 5 of which were novel. The frequency of CYP1B1 mutations in this cohort was comparable with other populations. We also detected an individual heterozygous for p.(Tyr81Asn) mutation, previously suggested to cause autosomal dominant primary open-angle glaucoma....

  5. Epigenetic Regulation of Angiogenesis by JARID1B-Induced Repression of HOXA5

    DEFF Research Database (Denmark)

    Fork, Christian; Gu, Lunda; Hitzel, Juliane

    2015-01-01

    OBJECTIVE: Altering endothelial biology through epigenetic modifiers is an attractive novel concept, which is, however, just in its beginnings. We therefore set out to identify chromatin modifiers important for endothelial gene expression and contributing to angiogenesis. APPROACH AND RESULTS...... of JARID1B in the vascular system, Jarid1b knockout mice were studied. As global knockout results in increased mortality and developmental defects, tamoxifen-inducible and endothelial-specific knockout mice were generated. Acute knockout of Jarid1b attenuated retinal angiogenesis and endothelial sprout...

  6. MODIS/Terra Calibrated Radiances 5-Min L1B Swath 1km V005

    Data.gov (United States)

    National Aeronautics and Space Administration — The MODIS Level 1B data set contains calibrated and geolocated at-aperture radiances for 36 discrete bands located in the 0.4 to 14.4 micron region of...

  7. MODIS/Terra Calibrated Radiances 5-Min L1B Swath 1km - NRT

    Data.gov (United States)

    National Aeronautics and Space Administration — The MODIS Level 1B Near Real Time (NRT) data set contains calibrated and geolocated at-aperture radiances for 36 discrete bands located in the 0.4 to 14.4 micron...

  8. Function of PTP1B in Neuroendocrine Differentiation of Prostate Cancer

    National Research Council Canada - National Science Library

    Huang, Jiaoti

    2008-01-01

    ... differentiation of prostate cancer cells, particularly the relationship of PTP1B to IL-8 signaling through its receptors CXCR1 and CXCR2, to IGF-1 receptor signaling through PI3 kinase/AKT/mTOR pathway...

  9. Tissue-specific alternative splicing and expression of ATP1B2 gene

    African Journals Online (AJOL)

    user6

    2012-05-15

    May 15, 2012 ... retention; these isoforms were found in liver, kidney, muscle and breast tissues. ... lower levels than the complete ATP1B2 gene transcript in all the ... temperature. ... growth, differentiation, and disease (Zhou et al., 2002;.

  10. 20 CFR 655.736 - What are H-1B-dependent employers and willful violators?

    Science.gov (United States)

    2010-04-01

    ... Fashion Models, and Requirements for Employers Seeking To Employ Nonimmigrants on H-1b1 and E-3 Visas in... not include bona fide consultants and independent contractors. For purposes of this section, the...

  11. ASTER Expedited L1B Registered Radiance at the Sensor V003

    Data.gov (United States)

    National Aeronautics and Space Administration — The Expedited ASTER Level-1B Registered Radiance at the Sensor data set is produced with the express purpose of providing ASTER Science Team members data of their...

  12. The new powder diffractometer D1B of the Institut Laue Langevin

    Science.gov (United States)

    Puente Orench, I.; Clergeau, J. F.; Martínez, S.; Olmos, M.; Fabelo, O.; Campo, J.

    2014-11-01

    D1B is a medium resolution high flux powder diffractometer located at the Institut Laue Langevin, ILL. D1B a suitable instrument for studying a large variety of polycrystalline materials. D1B runs since 1998 as a CRG (collaborating research group) instrument, being exploited by the CNRS (Centre National de la Recherche Scientifique, France) and CSIC (Consejo Superior de Investigaciones Cientificas, Spain). In 2008 the Spanish CRG started an updating program which included a new detector and a radial oscillating collimator (ROC). The detector, which has a sensitive height of 100mm, covers an angular range of 128°. Its 1280 gold wires provide a neutron detection point every 0.1°. The ROC is made of 198 gadolinium- based absorbing collimation blades, regular placed every 0.67°. Here the present characteristics of D1B are reviewed and the different experimental performances will be presented.

  13. CYP1B1 and myocilin gene mutations in Egyptian patients with ...

    African Journals Online (AJOL)

    Mahmoud R. Fassad

    2016-08-09

    Aug 9, 2016 ... Abstract Purpose: Primary congenital glaucoma (PCG) accounts for 26–29% of childhood ... Conclusion: The current study further endorses the role of CYP1B1 mutations in the etiology of ..... There is no conflict of interest.

  14. Protein Tyrosine Phosphatase 1B Inhibitors from the Roots of Cudrania tricuspidata

    Directory of Open Access Journals (Sweden)

    Tran Hong Quang

    2015-06-01

    Full Text Available A chemical investigation of the methanol extract from the roots of Cudrania tricuspidata resulted in the isolation of 16 compounds, including prenylated xanthones 1–9 and flavonoids 10–16. Their structures were identified by NMR spectroscopy and mass spectrometry and comparisons with published data. Compounds 1–9 and 13–16 significantly inhibited PTP1B activity in a dose dependent manner, with IC50 values ranging from 1.9–13.6 μM. Prenylated xanthones showed stronger PTP1B inhibitory effects than the flavonoids, suggesting that they may be promising targets for the future discovery of novel PTP1B inhibitors. Furthermore, kinetic analyses indicated that compounds 1 and 13 inhibited PTP1B in a noncompetitive manner; therefore, they may be potential lead compounds in the development of anti-obesity and -diabetic agents.

  15. IceBridge Scintrex CS-3 Cesium Magnetometer L1B Geolocated Magnetic Anomalies, Version 1

    Data.gov (United States)

    National Aeronautics and Space Administration — The NASA IceBridge Scintrex CS-3 Cesium Magnetometer L1B Geolocated Magnetic Anomalies (IMCS31B) data set contains magnetic field readings taken over Greenland using...

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

    International Nuclear Information System (INIS)

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

    1991-01-01

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

  17. Effects of serotonin (5-HT)1B receptor ligands on amphetamine-seeking behavior in rats.

    Science.gov (United States)

    Miszkiel, Joanna; Przegaliński, Edmund

    2013-01-01

    Numerous studies have indicated that serotonin (5-HT)1B receptor ligands affect the behavioral effects of psychostimulants (cocaine, amphetamine), including the reinforcing activities of these drugs. To substantiate a role for those receptors in incentive motivation for amphetamine, we used the extinction/reinstatement model to examine the effects of the 5-HT1B receptor ligands on the reinstatement of extinguished amphetamine-seeking behavior. Rats trained to self-administer amphetamine (0.06 mg/kg/infusion) subsequently underwent the extinction procedure. These rats were then tested for the amphetamine-primed or amphetamine-associated cue-induced reinstatement of extinguished amphetamine-seeking behavior. The 5-HT1B receptor antagonist SB 216641 (5-7.5 mg/kg) attenuated the amphetamine (1.5 mg/kg)- and the amphetamine-associated cue combined with the threshold dose of amphetamine (0.5 mg/kg)-induced reinstatement of amphetamine-seeking behavior. The 5-HT1B receptor agonist CP 94253 (1.25-5 mg/kg) also inhibited the amphetamine-seeking behavior induced by amphetamine (1.5 mg/kg) but not by the cue combined with the threshold dose of amphetamine. The inhibitory effect of CP94253 on amphetamine-seeking behavior remained unaffected by the 5-HT1B receptor antagonist. Our results indicate that tonic activation of 5-HT1B receptors is involved in amphetamine- and cue-induced reinstatement of amphetamine-seeking behavior and that the inhibitory effects of 5-HT1B receptor antagonists on these phenomena are directly related to the motivational aspects of amphetamine abuse. The inhibitory effect of CP 94253 on amphetamine-seeking behavior seems to be unrelated to 5-HT1B receptor activation and may result from a general reduction of motivation.

  18. Docking of oxalyl aryl amino benzoic acid derivatives into PTP1B

    Science.gov (United States)

    Verma, Neelam; Mittal, Minakshi; Verma, Raman kumar

    2008-01-01

    Protein Tyrosine Phosphatases (PTPs) that function as negative regulators of the insulin signaling cascade have been identified as novel targets for the therapeutic enhancement of insulin action in insulin resistant disease states. Reducing Protein Tyrosine Phosphatase1B (PTP1B) abundance not only enhances insulin sensitivity and improves glucose metabolism but also protects against obesity induced by high fat feeding. PTP1B inhibitors such as Formylchromone derivatives, 1, 2-Naphthoquinone derivatives and Oxalyl aryl amino benzoic derivatives may eventually find an important clinical role as insulin sensitizers in the management of Type-II Diabetes and metabolic syndrome. We have carried out docking of modified oxalyl aryl amino benzoic acid derivatives into three dimensional structure of PTP1B using BioMed CAChe 6.1. These compounds exhibit good selectivity for PTP1B over most of phosphatases in selectivity panel such as SHP-2, LAR, CD45 and TCPTP found in literature. This series of compounds identified the amino acid residues such as Gly220 and Arg221 are important for achieving specificity via H-bonding interactions. Lipophilic side chain of methionine in modified oxalyl aryl amino benzoic acid derivative [1b (a2, b2, c1, d)] lies in closer vicinity of hydrophobic region of protein consisted of Meth258 and Phe52 in comparison to active ligand. Docking Score in [1b (a2, b2, c1, d)] is -131.740Kcal/mol much better than active ligand score -98.584Kcal/mol. This information can be exploited to design PTP1B specific inhibitors. PMID:19238234

  19. Anti-Chol-1 antigen, GQ1bα, antibodies are associated with Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Toshio Ariga

    Full Text Available The interaction of amyloid β-proteins (Aβ with membrane gangliosides has been reported to be an early event in Aβ fibril formation in Alzheimer's disease (AD. Neuronal degeneration in AD has been postulated to be associated with the presence of anti-ganglioside antibodies in patient sera. Using an enzyme-linked immunosorbent assay (ELISA and high-performance thin-layer chromatography (HPTLC immunostaining, sera from 27 individuals (10 with AD, 6 with vascular dementia (VD, and 11 non-demented age-matched pathological controls were examined in order to detect anti-glycosphingolipid (GSL antibodies, including anti-cholinergic-specific antigen (Chol-1α; GQ1bα antibodies. All sera had natural antibodies against ganglio-N-tetraosyl gangliosides (brain-type gangliosides. However, sera of demented patients with AD and VD had significantly higher titers of anti-GSL antibodies than those in age-matched pathological controls. Although most serum antibodies, including anti- GM1, -GT1b, -GQ1b, -GQ1bα, were of the IgM type, the presence of the IgG type antibodies was also significantly elevated in the sera of demented patients with AD. Anti-GT1b antibodies of the IgG type were elevated in AD (90%, 9 of 10 cases and VD (100%, respectively. Most surprisingly, anti-GQ1bα antibodies (IgM were found in 90% (9/10 and 100% (6/6 in the sera of patients with AD and VD, respectively. Since GQ1bα is present in the cerebral cortex and hippocampus, the presence of anti-GQ1bα antibodies may play an important role in disrupting cholinergic synaptic transmission and may participate in the pathogenesis of dementia. We conclude that elevated anti-GSL antibody titers may be useful as an aid for clinical diagnosis of those dementias.

  20. Cloning and tissue expression of cytochrome P450 1B1 and 1C1 ...

    African Journals Online (AJOL)

    Cytochrome P450 1 (CYP1) is widely used as an indicator of exposure to environmental contaminants. In the study, two full-length complementary DNAs encode for CYP1B1 and CYP1C1 were cloned from medaka liver exposed to 500 ppb β-naphthoflavone for 24 h. CYP1B1, having 1984 bp, contains an open reading ...

  1. Unit 1b: A General Approach to the Teaching of Architecture

    DEFF Research Database (Denmark)

    Toft, Anne Elisabeth

    2011-01-01

    The chapter presents the overall academic aims of the teaching at Unit 1b and how these were implemented in the curriculum for 2009/2010. The section includes considerations about learning targets, method, discourse, pedagogy and didactics.......The chapter presents the overall academic aims of the teaching at Unit 1b and how these were implemented in the curriculum for 2009/2010. The section includes considerations about learning targets, method, discourse, pedagogy and didactics....

  2. Synthesis of Al-5Ti-1B Refiner by Melt Reaction Method

    OpenAIRE

    LI He; CHAI Li-hua; MA Teng-fei; CHEN Zi-yong

    2017-01-01

    Al-5Ti-1B refiner was successfully prepared by melt reaction method. Through the thermodynamics calculation, the initial reaction temperature was determined. The influence of reaction temperature on microstructure and absorption rate of the alloy was investigated. The phase and microstructure of the alloy were observed by X-ray diffraction, scanning electron microscope and energy dispersive spectrometer. The Al-5Ti-1B refiner was extruded at high temperature to wire with the diameter of 9.5mm...

  3. A Contextual Fire Detection Algorithm for Simulated HJ-1B Imagery

    Directory of Open Access Journals (Sweden)

    Xiangsheng Kong

    2009-02-01

    Full Text Available The HJ-1B satellite, which was launched on September 6, 2008, is one of the small ones placed in the constellation for disaster prediction and monitoring. HJ-1B imagery was simulated in this paper, which contains fires of various sizes and temperatures in a wide range of terrestrial biomes and climates, including RED, NIR, MIR and TIR channels. Based on the MODIS version 4 contextual algorithm and the characteristics of HJ-1B sensor, a contextual fire detection algorithm was proposed and tested using simulated HJ-1B data. It was evaluated by the probability of fire detection and false alarm as functions of fire temperature and fire area. Results indicate that when the simulated fire area is larger than 45 m2 and the simulated fire temperature is larger than 800 K, the algorithm has a higher probability of detection. But if the simulated fire area is smaller than 10 m2, only when the simulated fire temperature is larger than 900 K, may the fire be detected. For fire areas about 100 m2, the proposed algorithm has a higher detection probability than that of the MODIS product. Finally, the omission and commission error were evaluated which are important factors to affect the performance of this algorithm. It has been demonstrated that HJ-1B satellite data are much sensitive to smaller and cooler fires than MODIS or AVHRR data and the improved capabilities of HJ-1B data will offer a fine opportunity for the fire detection.

  4. 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.

  5. Design, synthesis and biological evaluation of uncharged catechol derivatives as selective inhibitors of PTP1B.

    Science.gov (United States)

    Li, Xiang-Qian; Xu, Qi; Luo, Jiao; Wang, Li-Jun; Jiang, Bo; Zhang, Ren-Shuai; Shi, Da-Yong

    2017-08-18

    Protein tyrosine phosphatases 1B (PTP1B) is a promising and validated therapeutic target to effectively treat T2DM and obesity. However, the development of charged PTP1B inhibitors was restricted due to their low cell permeability and poor bioavailability. Based on active natural products, two series of uncharged catechol derivatives were identified as PTP1B inhibitors by targeting a secondary aryl phosphate-binding site as well as the catalytic site. The most potent inhibitor 22 showed an IC 50 of 0.487 μM against PTP1B and strong selectivity (27-fold) over TCPTP. Kinetic studies were also performed that 22 act as a competitive PTP1B inhibitor. The treatment of C2C12 myotubes with 22 markedly increased the phosphorylation levels of IRβ, Akt and IRS1 phosphorylation. The similarity of its action profiling with that produced by insulin suggested its potential as a new non-insulin-dependent drug candidate. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  6. Association of PTP1B with Outcomes of Breast Cancer Patients who Underwent Neoadjuvant Chemotherapy

    Directory of Open Access Journals (Sweden)

    Monica M. Rivera Franco

    2016-01-01

    Full Text Available 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 overexpression and pCR; however, given the limited sample and heterogeneous treatment in our cohort, this hypothesis cannot be excluded.

  7. ARID1B is a specific vulnerability in ARID1A-mutant cancers.

    Science.gov (United States)

    Helming, Katherine C; Wang, Xiaofeng; Wilson, Boris G; Vazquez, Francisca; Haswell, Jeffrey R; Manchester, Haley E; Kim, Youngha; Kryukov, Gregory V; Ghandi, Mahmoud; Aguirre, Andrew J; Jagani, Zainab; Wang, Zhong; Garraway, Levi A; Hahn, William C; Roberts, Charles W M

    2014-03-01

    Recent studies have revealed that ARID1A, encoding AT-rich interactive domain 1A (SWI-like), is frequently mutated across a variety of human cancers and also has bona fide tumor suppressor properties. Consequently, identification of vulnerabilities conferred by ARID1A mutation would have major relevance for human cancer. Here, using a broad screening approach, we identify ARID1B, an ARID1A homolog whose gene product is mutually exclusive with ARID1A in SWI/SNF complexes, as the number 1 gene preferentially required for the survival of ARID1A-mutant cancer cell lines. We show that loss of ARID1B in ARID1A-deficient backgrounds destabilizes SWI/SNF and impairs proliferation in both cancer cells and primary cells. We also find that ARID1A and ARID1B are frequently co-mutated in cancer but that ARID1A-deficient cancers retain at least one functional ARID1B allele. These results suggest that loss of ARID1A and ARID1B alleles cooperatively promotes cancer formation but also results in a unique functional dependence. The results further identify ARID1B as a potential therapeutic target for ARID1A-mutant cancers.

  8. The analysis of correlation between IL-1B gene expression and genotyping in multiple sclerosis patients.

    Science.gov (United States)

    Heidary, Masoumeh; Rakhshi, Nahid; Pahlevan Kakhki, Majid; Behmanesh, Mehrdad; Sanati, Mohammad Hossein; Sanadgol, Nima; Kamaladini, Hossein; Nikravesh, Abbas

    2014-08-15

    IL-1B is released by monocytes, astrocytes and brain endothelial cells and seems to be involved in inflammatory reactions of the central nervous system (CNS) in multiple sclerosis (MS). This study aims to evaluate the expression level of IL-1B mRNA in peripheral blood mononuclear cells (PBMCs), genotype the rs16944 SNP and find out the role of this SNP on the expression level of IL-1B in MS patients. We found that the expression level of IL-1B in MS patients increased 3.336 times more than controls in PBMCs but the rs16944 SNP in the promoter region of IL-1B did not affect the expression level of this gene and there was not association of this SNP with MS in the examined population. Also, our data did not reveal any correlation between normalized expressions of IL-1B gene with age of participants, age of onset, and disease duration. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Arid1b haploinsufficient mice reveal neuropsychiatric phenotypes and reversible causes of growth impairment.

    Science.gov (United States)

    Celen, Cemre; Chuang, Jen-Chieh; Luo, Xin; Nijem, Nadine; Walker, Angela K; Chen, Fei; Zhang, Shuyuan; Chung, Andrew S; Nguyen, Liem H; Nassour, Ibrahim; Budhipramono, Albert; Sun, Xuxu; Bok, Levinus A; McEntagart, Meriel; Gevers, Evelien F; Birnbaum, Shari G; Eisch, Amelia J; Powell, Craig M; Ge, Woo-Ping; Santen, Gijs We; Chahrour, Maria; Zhu, Hao

    2017-07-11

    Sequencing studies have implicated haploinsufficiency of ARID1B , a SWI/SNF chromatin-remodeling subunit, in short stature (Yu et al., 2015), autism spectrum disorder (O'Roak et al., 2012), intellectual disability (Deciphering Developmental Disorders Study, 2015), and corpus callosum agenesis (Halgren et al., 2012). In addition, ARID1B is the most common cause of Coffin-Siris syndrome, a developmental delay syndrome characterized by some of the above abnormalities (Santen et al., 2012; Tsurusaki et al., 2012; Wieczorek et al., 2013). We generated Arid1b heterozygous mice, which showed social behavior impairment, altered vocalization, anxiety-like behavior, neuroanatomical abnormalities, and growth impairment. In the brain, Arid1b haploinsufficiency resulted in changes in the expression of SWI/SNF-regulated genes implicated in neuropsychiatric disorders. A focus on reversible mechanisms identified Insulin-like growth factor (IGF1) deficiency with inadequate compensation by Growth hormone-releasing hormone (GHRH) and Growth hormone (GH), underappreciated findings in ARID1B patients. Therapeutically, GH supplementation was able to correct growth retardation and muscle weakness. This model functionally validates the involvement of ARID1B in human disorders, and allows mechanistic dissection of neurodevelopmental diseases linked to chromatin-remodeling.

  10. Microstructure and grain refining performance of melt-spun Al-5Ti-1B master alloy

    International Nuclear Information System (INIS)

    Zhang Zhonghua; Bian Xiufang; Wang Yan; Liu Xiangfa

    2003-01-01

    In the present work, the microstructure and grain refining performance of the melt-spun Al-5Ti-1B (wt%) master alloy have been investigated, using X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), and grain refining tests. It has been found that the microstructure of the melt-spun Al-5Ti-1B master alloy is mainly composed of two phases: metastable, supersaturated α-Al solid solution and uniformly dispersed TiB 2 particles, quite different from that of the rod-like alloy consisting of three phases: α-Al, blocky TiAl 3 , and clusters of TiB 2 particles. Quenching temperatures and wheel speeds (cooling rates), however, have no obvious effect on the microstructure of the melt-spun Al-5Ti-1B alloy. Grain refining tests show that rapid solidification has a significant effect on the grain refining performance of Al-5Ti-1B alloy and leads to the great increase of nucleation rate of the alloy. Nevertheless, the melt-spun Al-5Ti-1B master alloy prepared at different wheel speeds and quenching temperatures possesses the similar grain refining performance. The reasons for the microstructure formation and the improvement of the grain refining performance of the melt-spun Al-5Ti-1B master alloy have been also discussed

  11. Interferon beta-1b reduces black holes in a randomised trial of clinically isolated syndrome.

    Science.gov (United States)

    Nagtegaal, Gijsbert J A; Pohl, Christoph; Wattjes, Mike P; Hulst, Hanneke E; Freedman, Mark S; Hartung, Hans-Peter; Miller, David; Montalban, Xavier; Kappos, Ludwig; Edan, Gilles; Pleimes, Dirk; Beckman, Karola; Stemper, Brigitte; Polman, Christoph H; Sandbrink, Rupert; Barkhof, Frederik

    2014-02-01

    Multiple sclerosis (MS) is characterised by inflammatory lesions of the central nervous system. Interferon beta-1b (IFNB-1b) has been shown to improve clinical and magnetic resonance imaging (MRI) measures for patients with MS. To evaluate whether IFNB-1b in patients presenting with clinically isolated syndromes (CIS) prevented persisting T1 hypointensities on MRI (persistent black holes (PBHs)). In the placebo-controlled phase, patients (n = 468) were initially randomised to IFNB-1b (n = 292) or placebo (n = 176) for two years or clinically definite MS (CDMS). In the open-label phase (n = 418), both groups were offered IFNB-1b for up to five years. Lesions were classified as PBHs if T1 hypointensity persisted throughout the last available scan (minimum time one year). A total of 435 patients were evaluable for analysis. The number of PBHs/patient was lower in the early rather than the delayed treatment arm during both phases (.42 vs .71, p = .0102 and .70 vs 1.17, p = .0121). Exploratory analyses identified baseline characteristics that affected rate of conversion. Although the rate of lesions that converted to PBH showed no significant differences between groups, the numbers of PBHs per patient out of new lesions was significantly lower in IFNB-1b patients compared to patients on placebo. NCT00544037.

  12. Jasmonate signalling in Arabidopsis involves SGT1b-HSP70-HSP90 chaperone complexes.

    Science.gov (United States)

    Zhang, Xue-Cheng; Millet, Yves A; Cheng, Zhenyu; Bush, Jenifer; Ausubel, Frederick M

    Plant hormones play pivotal roles in growth, development and stress responses. Although it is essential to our understanding of hormone signalling, how plants maintain a steady state level of hormone receptors is poorly understood. We show that mutation of the Arabidopsis thaliana co-chaperone SGT1b impairs responses to the plant hormones jasmonate, auxin and gibberellic acid, but not brassinolide and abscisic acid, and that SGT1b and its homologue SGT1a are involved in maintaining the steady state levels of the F-box proteins COI1 and TIR1, receptors for jasmonate and auxin, respectively. The association of SGT1b with COI1 is direct and is independent of the Arabidopsis SKP1 protein, ASK1. We further show that COI1 is a client protein of SGT1b-HSP70-HSP90 chaperone complexes and that the complexes function in hormone signalling by stabilizing the COI1 protein. This study extends the SGT1b-HSP90 client protein list and broadens the functional scope of SGT1b-HSP70-HSP90 chaperone complexes.

  13. Effect of Al–5Ti–1B grain refiner on the microstructure, mechanical properties and acoustic emission characteristics of Al5052 aluminium alloy

    OpenAIRE

    Pattnaik, Amulya Bihari; Das, Satyabrat; Jha, Bharat Bhushan; Prasanth, Nedumbilly

    2015-01-01

    In the present investigation, the effect of Al–5Ti–1B grain refiner on the microstructure, mechanical properties and acoustic emission characteristics of Al 5052 aluminium alloy have been studied. Microstructural analysis showed the presence of primary α solid solution. No Al–Mg phase was found to be formed due to the presence of magnesium in the solid solution. The results indicated that the addition of Al–5Ti–1B grain refiner into the alloy caused a significant improvement in ultimate tensi...

  14. Prosocial effects of prolactin in male rats: Social recognition, social approach and social learning.

    Science.gov (United States)

    Donhoffner, Mary E; Al Saleh, Samar; Schink, Olivia; Wood, Ruth I

    2017-11-01

    Prolactin (PRL) and oxytocin (OT) are pituitary hormones essential for lactation, but also promote sexual behavior. OT stimulates social behaviors, such as recognition, approach, and learning, but less is known about PRL in these behaviors. Since PRL and OT have complementary functions in reproduction, we hypothesized that PRL increases social recognition, approach, and learning. Male Long-Evans rats received ovine PRL (oPRL; 0.5, 2.0 or 5.0mg/kg), the PRL antagonist bromocriptine (0.1, 3.0 or 5.0mg/kg) or saline 20 mins before testing for recognition of familiar vs. unfamiliar stimulus males. Saline controls preferred the unfamiliar male (psocial approach, we determined if PRL restores approach 2h after defeat by an aggressive male. Defeated rats avoided the aggressive male. 2mg/kg oPRL, before or after defeat, restored approach towards the aggressive male (psocial learning, we tested social transmission of food preference. Rats choose between two unfamiliar flavors, one of which they have previously been exposed to through interaction with a demonstrator rat. Vehicle controls preferred chow with the demonstrated flavor over the novel flavor. oPRL-treated rats were similar. Bromocriptine-treated rats failed to show a preference. When tested one week later, only oPRL-treated rats preferred the demonstrated flavor. The results suggest that PRL is required for social recognition and learning, and that increasing PRL enhances social memory and approach, similar to OT. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Receptor-mediated mechanism for the transport of prolactin from blood to cerebrospinal fluid

    International Nuclear Information System (INIS)

    Walsh, R.J.; Slaby, F.J.; Posner, B.I.

    1987-01-01

    Prolactin (PRL) interacts with areas of the central nervous system which reside behind the blood-brain barrier. While vascular PRL does not cross this barrier, it is readily accessible to the cerebrospinal fluid (CSF) from which it may gain access to the PRL-responsive areas of the brain. Studies were undertaken to characterize the mechanism responsible for the translocation of PRL from blood to CSF. Rats were given external jugular vein injections of [ 125 -I]iodo-PRL in the presence or absence of an excess of unlabeled ovine PRL (oPRL), human GH, bovine GH, or porcine insulin. CSF and choroid plexus were removed 60 min later. CSF samples were electrophoresed on sodium dodecyl sulfate-polyacrylamide slab gels and resultant autoradiographs were analyzed with quantitative microdensitometry. The data revealed that unlabeled lactogenic hormones, viz. oPRL and human GH, caused a statistically significant inhibition of [ 125 I]iodo-PRL transport from blood to CSF. In contrast, nonlactogenic hormones, viz bovine GH and insulin, had no effect on [ 125 I]iodo-PRL transport into the CSF. An identical pattern of competition was observed in the binding of hormone to the choroid plexus. Furthermore, vascular injections of [ 125 I]iodo-PRL administered with a range of concentrations of unlabeled oPRL revealed a dose-response inhibition in the transport of [ 125 I]iodo-PRL from blood to CSF. The study demonstrates that PRL enters the CSF by a specific, PRL receptor-mediated transport mechanism. The data is consistent with the hypothesis that the transport mechanism resides at the choroid plexus. The existence of this transport mechanism reflects the importance of the cerebroventricular system in PRL-brain interactions

  16. Macrophage colony-stimulating factor induces prolactin expression in rat pituitary gland.

    Science.gov (United States)

    Hoshino, Satoya; Kurotani, Reiko; Miyano, Yuki; Sakahara, Satoshi; Koike, Kanako; Maruyama, Minoru; Ishikawa, Fumio; Sakatai, Ichiro; Abe, Hiroyuki; Sakai, Takafumi

    2014-06-01

    We investigated the role of macrophage colony-stimulating factor (M-CSF) in the pituitary gland to understand the effect of M-CSF on pituitary hormones and the relationship between the endocrine and immune systems. When we attempted to establish pituitary cell lines from a thyrotropic pituitary tumor (TtT), a macrophage cell line, TtT/M-87, was established. We evaluated M-CSF-like activity in conditioned media (CM) from seven pituitary cell lines using TtT/M-87 cells. TtT/M-87 proliferation significantly increased in the presence of CM from TtT/GF cells, a pituitary folliculostellate (FS) cell line. M-CSF mRNA was detected in TtT/GF and MtT/E cells by reverse transcriptase-polymerase chain reaction (RT-PCR), and its expression in TtT/GF cells was increased in a lipopolysaccharide (LPS) dose-dependent manner. M-CSF mRNA expression was also increased in rat anterior pituitary glands by LPS. M-CSF receptor (M-CSFR) mRNA was only detected in TtT/ M-87 cells and increased in the LPS-stimulated rat pituitary glands. In rat pituitary glands, M-CSF and M-CSFR were found to be localized in FS cells and prolactin (PRL)-secreting cells, respectively, by immunohistochemistry. The PRL concentration in rat sera was significantly increased at 24 h after M-CSF administration, and mRNA levels significantly increased in primary culture cells of rat anterior pituitary glands. In addition, TNF-α mRNA was increased in the primary culture cells by M-CSF. These results revealed that M-CSF was secreted from FS cells and M-CSF regulated PRL expression in rat pituitary glands.

  17. Stimulatory effects of adenosine on prolactin secretion in the pituitary gland of the rat

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    D.L.W. Picanço-Diniz

    2002-07-01

    Full Text Available We investigated the effects of adenosine on prolactin (PRL secretion from rat anterior pituitaries incubated in vitro. The administration of 5-N-methylcarboxamidoadenosine (MECA, an analog agonist that preferentially activates A2 receptors, induced a dose-dependent (1 nM to 1 µM increase in the levels of PRL released, an effect abolished by 1,3-dipropyl-7-methylxanthine, an antagonist of A2 adenosine receptors. In addition, the basal levels of PRL secretion were decreased by the blockade of cyclooxygenase or lipoxygenase pathways, with indomethacin and nordihydroguaiaretic acid (NDGA, respectively. The stimulatory effects of MECA on PRL secretion persisted even after the addition of indomethacin, but not of NDGA, to the medium. MECA was unable to stimulate PRL secretion in the presence of dopamine, the strongest inhibitor of PRL release that works by inducing a decrease in adenylyl cyclase activity. Furthermore, the addition of adenosine (10 nM mimicked the effects of MECA on PRL secretion, an effect that persisted regardless of the presence of LiCl (5 mM. The basal secretion of PRL was significatively reduced by LiCl, and restored by the concomitant addition of both LiCl and myo-inositol. These results indicate that PRL secretion is under a multifactorial regulatory mechanism, with the participation of different enzymes, including adenylyl cyclase, inositol-1-phosphatase, cyclooxygenase, and lipoxygenase. However, the increase in PRL secretion observed in the lactotroph in response to A2 adenosine receptor activation probably was mediated by mechanisms involving regulation of adenylyl cyclase, independent of membrane phosphoinositide synthesis or cyclooxygenase activity and partially dependent on lipoxygenase arachidonic acid-derived substances.

  18. Decidual activin: its role in the apoptotic process and its regulation by prolactin.

    Science.gov (United States)

    Tessier, Christian; Prigent-Tessier, Anne; Bao, Lei; Telleria, Carlos M; Ferguson-Gottschall, Susan; Gibori, Gil B; Gu, Yan; Bowen-Shauver, Jennifer M; Horseman, Nelson D; Gibori, Geula

    2003-05-01

    Successful pregnancy requires profound differentiation and reorganization of the uterine tissues including, as pregnancy progresses, extensive apoptosis of decidual tissue to accommodate the developing conceptus. We have previously shown a positive correlation between expression of activin A and apoptosis in the decidua and have also shown that expression of activin A occurs at the time when prolactin (PRL) receptors disappear from decidual cells. The goals of this study were to examine whether activin A plays a role in decidual apoptosis and whether expression of activin A in the decidua is regulated by PRL and placental lactogens. Studies were carried out using primary rat decidual cells, a decidual cell line (GG-AD), and PRL null mice. Treatment of decidual cells with activin A significantly increased DNA degradation, caspase 3 activity, and caspase 3 mRNA expression. However, this effect was observed only in the absence of endogenous activin production by these cells. Addition of follistatin to decidual cells that were producing activin A decreased both caspase 3 activity and mRNA expression. Similarly, addition of activin-blocking antibodies to cultures of GG-AD cells, which also produce activin A, caused a reduction in both DNA degradation and caspase 3 activity. PRL and placental lactogens caused an inhibition of activin A mRNA expression in primary decidual cells. Even more convincingly, decidua of PRL null mice expressed abundant activin A at a time when no expression of this hormone is detected in wild-type mice and treatment of PRL null mice with PRL caused a profound inhibition of activin A mRNA expression. In summary, our investigations into the role and regulation of decidual activin have revealed that activin A can induce cell death in the decidua and that its expression is under tight regulation by PRL and placental lactogens.

  19. Differences in both glycosylation and binding properties between rat and mouse liver prolactin receptors.

    Science.gov (United States)

    Lascols, O; Cherqui, G; Munier, A; Picard, J; Capeau, J

    1994-05-01

    To investigate whether glycanic chains of prolactin receptors (PRL-R) play a role in hormone binding activity, comparison was made of rat and mouse liver solubilized receptors with respect to both their affinity for the hormone and their glycosylation properties. As compared with rat receptors, mouse receptors exhibited a 2-fold higher affinity for human growth hormone (hGH), the hormone being bound by both tissues with a lactogenic specificity. Along with this increased affinity, mouse receptors had a 2 lower M(r) relative to rat receptors (62 kDa versus 64 kDa as measured on hGH cross-linked receptors). These differences could be ascribed to different glycosylation properties of the receptors from the two species, as supported by the followings. 1) After treatment with endoglycosidase F (endo F), rat and mouse PRL-R no longer exhibited any difference in their M(r) (54 kDa for both cross-linked receptors). 2) Neuraminidase treatment increased by 37% the binding of hGH to mouse receptors, but was ineffective on the hormone-binding to rat receptors. Conversely, wheat germ agglutinin (WGA), another sialic acid specific probe, decreased hGH binding to rat receptors by 25%, but had no effect on this process for mouse ones. 3) Marked differences were observed in the recoveries of rat and mouse hormone-receptor (HR) complexes from ricin-1- (RCA1-), concanavalin A- (ConA-) and WGA-immobilized lectins. These differences were reduced (RCA1 and ConA) or abolished (WGA) after rat and mouse receptor desialylation by neuraminidase, a treatment which decreased the M(r) of both receptors by 2 kDa. Taken together, these results strongly suggest that the PRL-R from rat and mouse liver contain biantennary N-linked oligosaccharidic chains with distinct type of sialylation, which may account for their differential hormone-binding affinities.

  20. Prolactin-derived vasoinhibins increase anxiety- and depression-related behaviors.

    Science.gov (United States)

    Zamorano, Miriam; Ledesma-Colunga, Maria G; Adán, Norma; Vera-Massieu, Camila; Lemini, Maria; Méndez, Isabel; Moreno-Carranza, Bibiana; Neumann, Inga D; Thebault, Stéphanie; Martínez de la Escalera, Gonzalo; Torner, Luz; Clapp, Carmen

    2014-06-01

    The hormone prolactin (PRL) regulates neuroendocrine and emotional stress responses. It is found in the hypothalamus, where the protein is partially cleaved to vasoinhibins, a family of N-terminal antiangiogenic PRL fragments ranging from 14 to 18kDa molecular masses, with unknown effects on the stress response. Here, we show that the intracerebroventricular administration of a recombinant vasoinhibin, containing the first 123 amino acids of human PRL that correspond to a 14kDa PRL, exerts anxiogenic and depressive-like effects detected in the elevated plus-maze, the open field, and the forced swimming tests. To investigate whether stressor exposure affects the generation of vasoinhibins in the hypothalamus, the concentrations of PRL mRNA, PRL, and vasoinhibins were evaluated in hypothalamic extracts of virgin female rats immobilized for 30min at different time points after stress onset. The hypothalamic levels of PRL mRNA and protein were higher at 60min but declined at 360min to levels seen in non-stressed animals. The elevation of hypothalamic PRL did not correlate with the stress-induced increase in circulating PRL levels, nor was it modified by blocking adenohypophyseal PRL secretion with bromocriptine. A vasoinhibin having an electrophoretic migration rate corresponding to 17kDa was detected in the hypothalamus. Despite the elevation in hypothalamic PRL, the levels of this hypothalamic vasoinhibin were similar in stressed and non-stressed rats. Stress reduced the rate of cleavage of PRL to this vasoinhibin as shown by the incubation of recombinant PRL with hypothalamic extracts from stressed rats. These results suggest that vasoinhibins are potent anxiogenic and depressive factors and that stress increases PRL levels in the hypothalamus partly by reducing its conversion to vasoinhibins. The reciprocal interplay between PRL and vasoinhibins may represent an effective mechanism to regulate anxiety and depression. Copyright © 2014 Elsevier Ltd. All rights

  1. Isotocin Regulates Growth Hormone but Not Prolactin Release From the Pituitary of Ricefield Eels

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    Wei Yang

    2018-04-01

    Full Text Available The neurohypophyseal hormone oxytocin (Oxt has been shown to stimulate prolactin (Prl synthesis and release from the adenohypophysis in rats. However, little is known about the functional roles of Oxt-like neuropeptides in the adenohypophysis of non-mammalian vertebrates. In this study, cDNAs encoding ricefield eel oxytocin-like receptors (Oxtlr, namely isotocin (Ist receptor 1 (Istr1 and 2 (Istr2, were isolated and specific antisera were generated, respectively. RT-PCR and Western blot analysis detected the presence of both Istr1 and Istr2 in the brain and pituitary, but differential expression in some peripheral tissues, including the liver and kidney, where only Istr1 was detected. In the pituitary, immunoreactive Istr1 and Istr2 were differentially distributed, with the former mainly in adenohypophyseal cell layers adjacent to the neurohypophysis, whereas the latter in peripheral areas of the adenohypophysis. Double immunofluorescent images showed that immunostaining of Istr1, but not Istr2 was localized to growth hormone (Gh cells, but neither of them was expressed in Prl cells. Ist inhibited Gh release in primary pituitary cells of ricefield eels and increased Gh contents in the pituitary gland of ricefield eels at 6 h after in vivo administration. Ist inhibition of Gh release is probably mediated by cAMP, PKC/DAG, and IP3/Ca2+ pathways. In contrast, Ist did not affect either prl gene expression or Prl contents in primary pituitary cells. Results of this study demonstrated that Ist may not be involved in the regulation of Prl, but inhibit Gh release via Istr1 rather than Istr2 in ricefield eels, and provided evidence for the direct regulation of Gh cells by oxytocin-like neuropeptides in the pituitary of non-mammalian vertebrates.

  2. Isotocin Regulates Growth Hormone but Not Prolactin Release From the Pituitary of Ricefield Eels

    Science.gov (United States)

    Yang, Wei; Zhang, Ning; Shi, Boyang; Zhang, Shen; Zhang, Lihong; Zhang, Weimin

    2018-01-01

    The neurohypophyseal hormone oxytocin (Oxt) has been shown to stimulate prolactin (Prl) synthesis and release from the adenohypophysis in rats. However, little is known about the functional roles of Oxt-like neuropeptides in the adenohypophysis of non-mammalian vertebrates. In this study, cDNAs encoding ricefield eel oxytocin-like receptors (Oxtlr), namely isotocin (Ist) receptor 1 (Istr1) and 2 (Istr2), were isolated and specific antisera were generated, respectively. RT-PCR and Western blot analysis detected the presence of both Istr1 and Istr2 in the brain and pituitary, but differential expression in some peripheral tissues, including the liver and kidney, where only Istr1 was detected. In the pituitary, immunoreactive Istr1 and Istr2 were differentially distributed, with the former mainly in adenohypophyseal cell layers adjacent to the neurohypophysis, whereas the latter in peripheral areas of the adenohypophysis. Double immunofluorescent images showed that immunostaining of Istr1, but not Istr2 was localized to growth hormone (Gh) cells, but neither of them was expressed in Prl cells. Ist inhibited Gh release in primary pituitary cells of ricefield eels and increased Gh contents in the pituitary gland of ricefield eels at 6 h after in vivo administration. Ist inhibition of Gh release is probably mediated by cAMP, PKC/DAG, and IP3/Ca2+ pathways. In contrast, Ist did not affect either prl gene expression or Prl contents in primary pituitary cells. Results of this study demonstrated that Ist may not be involved in the regulation of Prl, but inhibit Gh release via Istr1 rather than Istr2 in ricefield eels, and provided evidence for the direct regulation of Gh cells by oxytocin-like neuropeptides in the pituitary of non-mammalian vertebrates.

  3. Prolactin-dependent modulation of organogenesis in the vertebrate: Recent discoveries in zebrafish.

    Science.gov (United States)

    Nguyen, Nhu; Stellwag, Edmund J; Zhu, Yong

    2008-11-01

    The scientific literature is replete with evidence of the multifarious functions of the prolactin (PRL)/growth hormone (GH) superfamily in adult vertebrates. However, little information is available on the roles of PRL and related hormones prior to the adult stage of development. A limited number of studies suggest that GH functions to stimulate glucose transport and protein synthesis in mouse blastocytes and may be involved during mammalian embryogenesis. In contrast, the evidence for a role of PRL during vertebrate embryogenesis is limited and controversial. Genes encoding GH/PRL hormones and their respective receptors are actively transcribed and translated in various animal models at different time points, particularly during tissue remodeling. We have addressed the potential function of GH/PRL hormones during embryonic development in zebrafish by the temporary inhibition of in vivo PRL translation. This treatment caused multiple morphological defects consistent with a role of PRL in embryonic-stage organogenesis. The affected organs and tissues are known targets of PRL activity in fish and homologous structures in mammalian species. Traditionally, the GH/PRL hormones are viewed as classical endocrine hormones, mediating functions through the circulatory system. More recent evidence points to cytokine-like actions of these hormones through either an autocrine or a paracrine mechanism. In some situations they could mimic actions of developmentally regulated genes as suggested by experiments in multiple organisms. In this review, we present similarities and disparities between zebrafish and mammalian models in relation to PRL and PRLR activity. We conclude that the zebrafish could serve as a suitable alternative to the rodent model to study PRL functions in development, especially in relation to organogenesis.

  4. Hormonal regulation of aquaporin 3: opposing actions of prolactin and cortisol in tilapia gill.

    Science.gov (United States)

    Breves, Jason P; Inokuchi, Mayu; Yamaguchi, Yoko; Seale, Andre P; Hunt, Bethany L; Watanabe, Soichi; Lerner, Darren T; Kaneko, Toyoji; Grau, E Gordon

    2016-09-01

    Aquaporins (Aqps) are expressed within key osmoregulatory tissues where they mediate the movement of water and selected solutes across cell membranes. We leveraged the functional plasticity of Mozambique tilapia (Oreochromis mossambicus) gill epithelium to examine how Aqp3, an aquaglyceroporin, is regulated in response to osmoregulatory demands. Particular attention was paid to the actions of critical osmoregulatory hormones, namely, prolactin (Prl), growth hormone and cortisol. Branchial aqp3 mRNA levels were modulated following changes in environmental salinity, with enhanced aqp3 mRNA expression upon transfer from seawater to freshwater (FW). Accordingly, extensive Aqp3 immunoreactivity was localized to cell membranes of branchial epithelium in FW-acclimated animals. Upon transferring hypophysectomized tilapia to FW, we identified that a pituitary factor(s) is required for Aqp3 expression in FW. Replacement with ovine Prl (oPrl) was sufficient to stimulate Aqp3 expression in hypophysectomized animals held in FW, an effect blocked by coinjection with cortisol. Both oPrl and native tilapia Prls (tPrl177 and tPrl188) stimulated aqp3 in incubated gill filaments in a concentration-related manner. Consistent with in vivo responses, coincubation with cortisol blocked oPrl-stimulated aqp3 expression in vitro Our data indicate that Prl and cortisol act directly upon branchial epithelium to regulate Aqp3 in tilapia. Thus, within the context of the diverse actions of Prl on hydromineral balance in vertebrates, we define a new role for Prl as a regulator of Aqp expression. © 2016 Society for Endocrinology.

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

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    Shrestha Priyadarsini

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

  6. Development of the radioimmunoassay for prolactin, vasopressin and argin in invasotocin in view of reproduction phenomena in normal conditions and under the action of environmental noxious agents

    International Nuclear Information System (INIS)

    Simionescu, L.

    1979-10-01

    Radioimmunoassay procedures for testosterone, thyroglobulin, gonadotropin-inhibiting urinary substance (GIS), prolactin, follicle-stimulating hormone, luteinizing hormone (LH) and vasopressin were developed with reagents either locally produced or obtained from other sources. Studies of the effects of a pesticide, Malathion, on serum prolactin, FSH and LH levels in rats and of the effects of two herbicides, Amitrol and Atrazin, on thyroglobulin levels in human thyroid cell cultures were carried out. In the former, significant effects of Malathion on serum prolactin, FSH and LH levels, depending on dose level and mode of administration, were observed. In the latter, thyroglobulin levels in the cell cultures were proved resistant to Amitrol and Atrazin. The significance of these findings is discussed

  7. Trivaric acid, a new inhibitor of PTP1b with potent beneficial effect on diabetes.

    Science.gov (United States)

    Sun, Wenlong; Zhang, Bowei; Zheng, Haizhou; Zhuang, Chunlin; Li, Xia; Lu, Xinhua; Quan, Chunshan; Dong, Yuesheng; Zheng, Zhihui; Xiu, Zhilong

    2017-01-15

    To screen a potential PTP1b inhibitor from the microbial origin-based compound library and to investigate the potential anti-diabetic effects of the inhibitor in vivo and determine its primary anti-diabetic mechanism in vitro and in silico. PTP1b inhibitory activity was measured using recombination protein as the enzyme and p-NPP as the substrate. The binding of the inhibitor to PTP1b was analysed by docking in silico and confirmed by ITC experiments. The intracellular signalling pathway was detected by Western blot analysis in HepG2 cells. The anti-diabetic effects were evaluated using a diabetic mice model in vivo. Among 545 microbial origin-based pure compounds tested, trivaric acid, a tridepside, was selected as a PTP1B inhibitor exhibiting strong inhibitory activity with an IC 50 of 173nM. Docking and ITC studies showed that trivaric acid was able to spontaneously bind to PTP1b and may inhibit PTP1b by blocking the catalytic domain of the phosphatase. Trivaric acid also enhanced the ability of insulin to stimulate the IR/IRS/Akt/GLUT2 pathway and increase the glucose consumption in HepG2 cells. In diabetic mice, trivaric acid that had been encapsulated into Eudrgit L100-5.5 showed significant anti-diabetic effects, improving insulin resistance, leptin resistance and lipid profile and weight control at doses of 5mg/kg and 50mg/kg. Trivaric acid is a potential lead compound in the search for anti-diabetic agents targeting PTP1b. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Protection against gamma-radiation injury by protein tyrosine phosphatase 1B

    Directory of Open Access Journals (Sweden)

    Marina Mojena

    2018-07-01

    Full Text Available Protein tyrosine phosphatase 1B (PTP1B is widely expressed in mammalian tissues, in particular in immune cells, and plays a pleiotropic role in dephosphorylating many substrates. Moreover, PTP1B expression is enhanced in response to pro-inflammatory stimuli and to different cell stressors. Taking advantage of the use of mice deficient in PTP1B we have investigated the effect of γ-radiation in these animals and found enhanced lethality and decreased respiratory exchange ratio vs. the corresponding wild type animals. Using bone-marrow derived macrophages and mouse embryonic fibroblasts (MEFs from wild-type and PTP1B-deficient mice, we observed a differential response to various cell stressors. PTP1B-deficient macrophages exhibited an enhanced response to γ-radiation, UV-light, LPS and S-nitroso-glutathione. Macrophages exposed to γ-radiation show DNA damage and fragmentation, increased ROS production, a lack in GSH elevation and enhanced acidic β-galactosidase activity. Interestingly, these differences were not observed in MEFs. Differential gene expression analysis of WT and KO macrophages revealed that the main pathways affected after irradiation were an up-regulation of protein secretion, TGF-β signaling and angiogenesis among other, and downregulation of Myc targets and Hedgehog signaling. These results demonstrate a key role for PTP1B in the protection against the cytotoxicity of irradiation in intact animal and in macrophages, which might be therapeutically relevant. Keywords: Protein tyrosine phosphatase, Cell viability, Irradiation sensitivity, Lethality, p53

  9. Upstream ORF affects MYCN translation depending on exon 1b alternative splicing

    International Nuclear Information System (INIS)

    Besançon, Roger; Puisieux, Alain; Valsesia-Wittmann, Sandrine; Locher, Clara; Delloye-Bourgeois, Céline; Furhman, Lydie; Tutrone, Giovani; Bertrand, Christophe; Jallas, Anne-Catherine; Garin, Elisabeth

    2009-01-01

    The MYCN gene is transcribed into two major mRNAs: one full-length (MYCN) and one exon 1b-spliced (MYCN Δ1b ) mRNA. But nothing is known about their respective ability to translate the MYCN protein. Plasmids were prepared to enable translation from the upstream (uORF) and major ORF of the two MYCN transcripts. Translation was studied after transfection in neuroblastoma SH-EP cell line. Impact of the upstream AUG on translation was evaluated after directed mutagenesis. Functional study with the two MYCN mRNAs was conducted by a cell viability assay. Existence of a new protein encoded by the MYCN Δ1b uORF was explored by designing a rabbit polyclonal antibody against a specific epitope of this protein. Both are translated, but higher levels of protein were seen with MYCN Δ1b mRNA. An upstream ORF was shown to have positive cis-regulatory activity on translation from MYCN but not from MYCN Δ1b mRNA. In transfected SH-EP neuroblastoma cells, high MYCN dosage obtained with MYCN Δ1b mRNA translation induces an antiapoptotic effect after serum deprivation that was not observed with low MYCN expression obtained with MYCN mRNA. Here, we showed that MYCNOT: MYCN Overlap Transcript, a new protein of unknown function is translated from the upstream AUG of MYCN Δ1b mRNA. Existence of upstream ORF in MYCN transcripts leads to a new level of MYCN regulation. The resulting MYCN dosage has a weak but significant anti-apoptotic activity after intrinsic apoptosis induction

  10. Haploinsufficiency of BAZ1B contributes to Williams syndrome through transcriptional dysregulation of neurodevelopmental pathways.

    Science.gov (United States)

    Lalli, Matthew A; Jang, Jiwon; Park, Joo-Hye C; Wang, Yidi; Guzman, Elmer; Zhou, Hongjun; Audouard, Morgane; Bridges, Daniel; Tovar, Kenneth R; Papuc, Sorina M; Tutulan-Cunita, Andreea C; Huang, Yadong; Budisteanu, Magdalena; Arghir, Aurora; Kosik, Kenneth S

    2016-04-01

    Williams syndrome (WS) is a neurodevelopmental disorder caused by a genomic deletion of ∼28 genes that results in a cognitive and behavioral profile marked by overall intellectual impairment with relative strength in expressive language and hypersocial behavior. Advancements in protocols for neuron differentiation from induced pluripotent stem cells allowed us to elucidate the molecular circuitry underpinning the ontogeny of WS. In patient-derived stem cells and neurons, we determined the expression profile of the Williams-Beuren syndrome critical region-deleted genes and the genome-wide transcriptional consequences of the hemizygous genomic microdeletion at chromosome 7q11.23. Derived neurons displayed disease-relevant hallmarks and indicated novel aberrant pathways in WS neurons including over-activated Wnt signaling accompanying an incomplete neurogenic commitment. We show that haploinsufficiency of the ATP-dependent chromatin remodeler, BAZ1B, which is deleted in WS, significantly contributes to this differentiation defect. Chromatin-immunoprecipitation (ChIP-seq) revealed BAZ1B target gene functions are enriched for neurogenesis, neuron differentiation and disease-relevant phenotypes. BAZ1B haploinsufficiency caused widespread gene expression changes in neural progenitor cells, and together with BAZ1B ChIP-seq target genes, explained 42% of the t