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Mariusz P Kowalewski - One of the best experts on this subject based on the ideXlab platform.
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Endocrine control of canine mammary neoplasms: serum reproductive hormone levels and tissue expression of steroid hormone, prolactin and growth hormone receptors
BMC Veterinary Research, 2015Co-Authors: Michèle Spoerri, Franco Guscetti, Alois Boos, Orsolya Balogh, Renata M Nowaczyk, Erika Michel, Iris M Reichler, Sonja Hartnack, Mariusz P KowalewskiAbstract:Background Neoplasms of the mammary gland are among the most common diseases in female domestic dogs ( Canis familiaris ). It is assumed that reproductive hormones influence tumorigenesis in this species, although the precise role of the endocrine milieu and reproductive state is subject to continuing discussion. In line with this, a recent systematic review of available data on the development of mammary neoplasms revealed weak evidence for risk reduction after neutering and an effect of age at neutering. Investigation of several hormone receptors has revealed decreased expression of estrogen receptor-alpha (ERα, ESR1), progesterone (P4) receptor (PGR), prolactin (PRL) receptor (PRLR) and growth hormone receptor (GHR) associated with neoplastic differentiation of mammary tissues. In other studies, increased levels of estrogens, progesterone and prolactin were found in serum and/or tissue homogenates of dogs with malignant neoplasms. However, the association between these entities within one animal population was never previously examined. Therefore, this study investigated the association between circulating serum concentrations of estradiol-17β, progesterone and prolactin, and gene expression of ERα (ESR1), ERβ (ESR2), PGR, PRLR, PRL and GHR, with respect to reproductive state (spayed vs. intact) and cycle stage (anestrus vs. Diestrus). Additionally, the expression of E-cadherin (CDH-1) was evaluated as a possible indicator of metastatic potential. Results For all receptors, the lowest gene expression was found in malignant tumors compared to normal tissues of affected dogs. Steroid levels were not influenced by their corresponding receptor expression in mammary neoplasms, but increased PRL levels were negatively associated with low PRLR gene expression in malignant tumors. The expression of CDH-1 was influenced by tumor malignancy and cycle stage, i.e ., the highest gene expression was found in benign mammary tumors in diestrous dogs compared to normal and malignant mammary tissues of anestrous and spayed dogs. Conclusions Herein, it has been confirmed that transformation towards malignant neoplasms is associated with significant reduction of gene expression of particular hormone receptors. Only PRLR in malignant tumors seems to be influenced by circulating PRL levels. In dogs, CDH-1 can be used as a prognostic factor; its expression, however, in benign tumors is influenced by cycle stage.
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lps challenged tnfα production prostaglandin secretion and tnfα tnfrs expression in the endometrium of domestic cats in estrus or Diestrus and in cats with pyometra or receiving medroxyprogesterone acetate
Mediators of Inflammation, 2014Co-Authors: Ewelina Jursza, Alois Boos, Mariusz P Kowalewski, Anna Z Szostek, Kiyoshi Okuda, Marta J SiemieniuchAbstract:Progesterone (P4) derivatives which are commonly used to block the cyclicity of domestic cats disturb the endocrine balance in the endometrium. The aims of this study were (i) to examine whether lipopolysaccharide (LPS) is responsible for enhancement of tumor necrosis factor-α (TNFα) secretion by the feline endometrial epithelial and stromal cells in vitro, (ii) to know whether immunolocalization of TNFα/TNFR1 and TNFR2 differs in cats at estrus or Diestrus, receiving medroxyprogesterone acetate and suffering from pyometra, and (iii) to determine if TNFα-challenged prostaglandin secretion is stopped by prostaglandin synthases inhibitors. A total of 37 domestic adult cats in estrus or Diestrus, receiving octane medroxyprogesterone or having clinical symptoms of pyometra, were enrolled in this study. The results obtained showed a distinct increase in LPS-challenged TNFα secretion in endometrial epithelial, but not stromal cells. TNFα augmented PG secretion was blocked by phospholipase A2 (PLA2) and cyclooxygeanase-2 (COX-2), but not by mitogen-activated protein kinase (MAPK) inhibitor. TNFα/TNFR1 and 2 protein expressions were limited mostly to the surface and glandular epithelium. TNFα/TNFRs protein was upregulated in the inflammatory uterus and hence may be involved in development of pathologic changes in the endometrial glands in cats receiving exogenous P4 as a hormonal contraceptive.
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gene transcription of tlr2 tlr4 lps ligands and prostaglandin synthesis enzymes are up regulated in canine uteri with cystic endometrial hyperplasia pyometra complex
Journal of Reproductive Immunology, 2010Co-Authors: Eveline Franco Da Silva, Mariusz P Kowalewski, S Leitao, Sofia Henriques, B Hoffmann, G Ferreiradias, Luis Costa, L MateusAbstract:Abstract Escherichia coli ( E. coli ) is the most frequent bacterium isolated in cases of cystic endometrial hyperplasia–pyometra complex, the most frequent endometrial disorder in the bitch. Toll-like receptors (TLRs) play an essential role in the innate immune system. The aim of this study was to compare transcription of genes encoding TLR2, TLR4 and LPS ligands (CD14, MD-2, LBP), prostaglandin synthesis enzymes (COX1, COX2, PGES1 and PGFS), and to compare COX1 and COX2 protein expression and PGE 2 and PGF 2α endometrial content in the endometrium of canine diestrous uteri with ( n =7) or without ( n =7) pyometra. All cases of pyometra were hyperplastic and E. coli was the only isolated bacteria, while diestrous normal uteri did not present signs of cystic endometrial hyperplasia and were negative for bacteriology. Except for COX1 , transcription of all genes was significantly higher in pyometra than in normal endometria. COX1 protein was observed in both normal and pyometra uteri, but COX2 protein was only present in pyometra cases. Endometrial PGE 2 and PGF 2α content were significantly higher in pyometra than in normal diestrous endometria. In conclusion, data obtained in this study provides evidence that pyometra-isolated E. coli induces the up-regulation of TLR2 and TLR4 genes in the canine diestrous endometrium. This up-regulation, which is probably the result of the stimulation by LPS and lipoprotein E. coli constituents, leads to the endometrial up-regulation of PG synthesis genes. This, in turn, results in a higher endometrial concentration of PGE 2 and PGF 2α , which may further regulate the local inflammatory response.
Barbara Woodside - One of the best experts on this subject based on the ideXlab platform.
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y1 receptor activation is involved in the effect of exogenous neuropeptide y on pup growth and the early termination of lactational Diestrus in the postpartum rat
Journal of Neuroendocrinology, 2002Co-Authors: D J Toufexis, S Yorozu, Barbara WoodsideAbstract:The effect of chronic administration of exogenous neuropeptide Y (NPY) and specific NPY receptor agonists and antagonists on reproductive function was examined in lactating rats. As previously demonstrated in our laboratory, chronic (7-day) intracerebroventricular (i.c.v.) NPY infusion (6 μg/day) from days 8-15 postpartum (pp) caused a significant decrease in milk production and an early termination of lactational Diestrus. Similar application of the mixed Y1/Y4/Y5 receptor agonist (Leu 3 1 , Pro 3 4 ) NPY (at 3, 6 and 9 μg/day) reproduced the effect of chronic NPY infusion on milk production in a dose-independent manner. Consistent with this effect, the potent Y1 antagonist/Y4 agonist, 1229U91, given concomitantly with NPY eliminated the decline in milk production. The Y2 receptor agonist, NPY 1 3 - 3 6 , had no effect on milk production at any of the doses used. Length of lactational Diestrus was reduced following administration of the Y2 agonist at 18 μg/day but not at 9 μg or 27 μg/day whereas (Leu 3 1 , Pro 3 4 ) NPY infusion had no effect on this parameter at any of the doses used. However, the group that was treated with NPY plus 1229U91 exhibited the usual length of lactational Diestrus, indicating that there is at least some Y1 involvement in the effects of NPY on lactational infertility. To test the possibility that the effects of NPY infusion are mediated through changes in circulating prolactin and progesterone, plasma concentrations of these hormones were measured on day 15 pp in NPY-, (Leu 3 1 , Pro 3 4 ) NPY- and vehicle-treated females. NPY-infused females had lower plasma prolactin concentrations than vehicle-infused dams but progesterone concentrations were similar across groups. Overall, these data indicate that chronic exogenous NPY-infusion n lactating females disrupts milk production and shortens lactational Diestrus, most likely through reducing prolactin secretion, and that this effect is mediated via Y1 receptor activity.
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the role of specific macronutrient availability in the effect of food restriction on length of lactational Diestrus in rats
Physiology & Behavior, 1998Co-Authors: Barbara Woodside, Alfonso Abizaid, Mirella CaporaleAbstract:Abstract WOODSIDE, B., A. ABIZAID AND M. CAPORALE. The role of specific macronutrient availability in the effect of food restriction on length of lactational Diestrus in rats. PHYSIOL BEHAV 64 (3) 409–414, 1998.—In lactating rats, food restriction for the first two weeks postpartum extends the period of lactational Diestrus by about 1 week. In these studies we investigated whether this effect results from caloric restriction or the reduced availability of a specific macronutrient. In Experiment 1 lactating rats nursing litters of eight pups were assigned to one of four conditions: 1) ad lib. fed; 2) protein-restricted; 3) carbohydrate-restricted; and 4) fat-restricted. Animals in all the restricted conditions were given access to 50% of ad lib. intake of the appropriate nutrient for Days 1–14 postpartum and ad lib. access to the other two macronutrients. In Experiment 2, ad lib. supplementation from one macronutrient source was provided to lactating rats given restricted access to a composite diet. No differential effect of specific macronutrient deprivation or supplementation on length of lactational Diestrus was observed in these studies. Thus, the results of both studies are consistent with the hypothesis that caloric restriction plays a primary role in inducing the prolongation of lactational Diestrus in food-restricted rats.
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role of the nutritional status of the litter and length and frequency of mother litter contact bouts in prolonging lactational Diestrus in rats
Hormones and Behavior, 1995Co-Authors: Barbara Woodside, James E JansAbstract:Abstract Food restricting lactating rat dams over the first 2 weeks of lactation results in a prolongation of the period of lactational Diestrus. Such food restriction has not only a direct effect on the dam but also the pups are undernourished, and the pattern of dam-litter contact is also changed. In a series of studies, we investigated the effects of nursing undernourished pups and the change in dam-litter interaction on the prolongation of lactational Diestrus. While nursing undernourished pups in the last 2 weeks of lactation is sufficient to extend lactational Diestrus in ad lib-fed dams nursing well-nourished pups in the last 2 weeks of lactation is not necessary for the prolongation of lactational Diestrus seen in food-restricted dams. Further, neither nursing underfed pups nor increased nest time in the first 2 weeks postpartum are necessary factors for the prolongation of lactational Diestrus in food-restricted dams.
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effects of food restriction on the length of lactational Diestrus in rats
Hormones and Behavior, 1991Co-Authors: Barbara WoodsideAbstract:The effect of food restriction (60% of an ad lib ration) for the first 14 days postpartum on serum progesterone levels and the duration of lactational Diestrus was determined in rat dams nursing litters of eight pups. Food restricted dams showed a longer period of lactational Diestrus than ad lib fed dams. Food restriction also caused an increase in progesterone levels that was maintained beyond the period of food restriction itself. Treatment with the dopamine agonist bromocryptine mesylate (0.5 mg/day) either from Day 1 or Day 9 postpartum onward induced early termination of lactational Diestrus in both ad lib and food restricted dams but the effect was more rapid in the ad lib fed than in the food restricted females. In both cases, however, the effects of bromocryptine administration on milk delivery showed a similar time course providing indirect evidence that prolactin suppression was equivalent under both diet conditions. These data suggest that food restriction during lactation results in increased progesterone levels that most likely result from increased prolactin release. Further, while prolactin suppression in food restricted dams reduces the duration of lactational Diestrus, the latency to do so is somewhat longer than that seen in ad lib fed females, suggesting that some other mechanism may also be operating to suppress ovulation in the food restricted female.
Marta J Siemieniuch - One of the best experts on this subject based on the ideXlab platform.
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lps challenged tnfα production prostaglandin secretion and tnfα tnfrs expression in the endometrium of domestic cats in estrus or Diestrus and in cats with pyometra or receiving medroxyprogesterone acetate
Mediators of Inflammation, 2014Co-Authors: Ewelina Jursza, Alois Boos, Mariusz P Kowalewski, Anna Z Szostek, Kiyoshi Okuda, Marta J SiemieniuchAbstract:Progesterone (P4) derivatives which are commonly used to block the cyclicity of domestic cats disturb the endocrine balance in the endometrium. The aims of this study were (i) to examine whether lipopolysaccharide (LPS) is responsible for enhancement of tumor necrosis factor-α (TNFα) secretion by the feline endometrial epithelial and stromal cells in vitro, (ii) to know whether immunolocalization of TNFα/TNFR1 and TNFR2 differs in cats at estrus or Diestrus, receiving medroxyprogesterone acetate and suffering from pyometra, and (iii) to determine if TNFα-challenged prostaglandin secretion is stopped by prostaglandin synthases inhibitors. A total of 37 domestic adult cats in estrus or Diestrus, receiving octane medroxyprogesterone or having clinical symptoms of pyometra, were enrolled in this study. The results obtained showed a distinct increase in LPS-challenged TNFα secretion in endometrial epithelial, but not stromal cells. TNFα augmented PG secretion was blocked by phospholipase A2 (PLA2) and cyclooxygeanase-2 (COX-2), but not by mitogen-activated protein kinase (MAPK) inhibitor. TNFα/TNFR1 and 2 protein expressions were limited mostly to the surface and glandular epithelium. TNFα/TNFRs protein was upregulated in the inflammatory uterus and hence may be involved in development of pathologic changes in the endometrial glands in cats receiving exogenous P4 as a hormonal contraceptive.
Margaret Stanley - One of the best experts on this subject based on the ideXlab platform.
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cytokine profile of mouse vaginal and uterus lymphocytes at estrus and Diestrus
Clinical & Developmental Immunology, 2005Co-Authors: Maria C. Lopez, Margaret StanleyAbstract:It is known that sex hormones regulate IgA and IgG levels in the female reproductive tract. Moreover, antigen presentation by uterine and vaginal epithelial cells is also under strict hormonal control. The effect of the estrous cycle on cytokine secretion by vaginal and uterine lymphoid cells has been examined in mice using simultaneous staining for cytoplasmic cytokines and surface markers after ex vivo culture with PMA/ionomycin in the presence of Brefeldin A, and flow cytometry analysis. Two different mice strains, BALB/c and C57BL/6 mice, were used. The most relevant finding was the increase in the proportion of vaginal cells secreting IFN-γ at Diestrus in both strains of mice. Other cytokines (IL-2 and IL-4) as well as some T cell subsets seemed to be modified in a strain dependent fashion. Data also suggest that NK cells are at least partially responsible for IFN-γ secretion. Our data indicate that vaginal and uterus lymphoid cells isolated at Diestrus were in vivo activated to secrete cytokines after ex vivo culture. IFN-γ seems to be the key cytokine, since it increases in both strains of mice.
Jennifer Johnson - One of the best experts on this subject based on the ideXlab platform.
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synthesis of uterine endometrial proteins during early Diestrus in the cyclic and pregnant dog and after estrogen and progesterone treatment
Biology of Reproduction, 1992Co-Authors: W C Buhi, Mariejoelle D Thatcher, Victor M Shille, I M Alvarez, Anne P Lannon, Jennifer JohnsonAbstract:The objectives of this study were to identify and characterize dog uterine endometrial proteins synthesized de novo in explant culture during early luteal phase, to examine distribution of these proteins prior to the embryo’s entering the uterus and during its free-floating period prior to implantation, and to examine regulation of endometrial proteins by estrogen and progesterone (P4) treatments. Uterine endometrium was collected from cyclic and pregnant bitches on Diestrus Days 3, 7, and 10 as determined by loss of cornlflcation of vaginal epitheium, and from ovariectomized dogs after treatment with corn oil, estrogen, F,, or estrogen followed by 1 or 2 wk of P4. Tissue was incubated in an explant culture system in the presence of l3HIleucme or [35SJmethionine. The rate of incorporation of [3Hlleucine into nondialyzable macromolecules indicated no significant change in rates of incorporation by status (pregnant vs. nonpregnant), day, or steroid treatment. Uterine endometrial-conditioned culture medium, analyzed by two-dimensional SDS-PAGE and fluorography, revealed a complex array of at least ten proteins or protein complexes in cyclic and pregnant bitches. No difference in protein pattern was detected by status; however, differences in distribution were apparent by day of cycle or early pregnancy. Two major proteins, cP5 (M, 54686) and cP6 (M, 23010) appeared to be differentially expressed. Expression of cP5, maximal on Diestrus Day 3, decreased as the cycle or pregnancy progressed to Diestrus Day 10. In contrast, expression of cP6, a minor protein on Diestrus Day 3, appeared to be up-regulated for each status to Day 10, wIth increased intensity and multiple isoelecthc and molecular-weight variants. In ovariectomized steroid-treated dogs, twodimensional SDS-PAGEshowed that pattern and distribution of specific proteins were affected by treatment. Acidic protein cPl (M, 87600), synthesized after corn oil and P4 treatment, was suppressed with estradiol (E2). Proteins cP2 (M, 40000 and M, 42000), present with all treatments, were intensified with P4. A high-M, basic protein complex (cP3) and acidic protein CR, were expressed with E, and maintained with P4 treatment. Proteins cP5 and cP6, while not induced by E2 or P4 alone, required E, priming for P4 induction. Protein cP5 was down-regulated while cP6 was up-regulated with P4 for 2 wk Proteins induced by estrogen followed by 1 or 2 wk of P4 treatments were similar to those released by endometrial explants collected from pregnant and cyclic bitches on Days 3, 7, and 10 of spontaneous Diestrus. Results of this study indicate that canine endometrium synthesizes de novo and secretes at least ten protein complexes, two of which are major proteins that are differentially expressed. Overall, protein expression appears different by day but not by status, suggesting that the preimplantation embryo does not have an effect on uterine endometrial protein synthesis and secretion. Expression of specific proteins during early Diestrus, however, appears to be in response to specific regimens of estrogen and P4 that mimic spontaneous early Diestrus.