The Experts below are selected from a list of 6570 Experts worldwide ranked by ideXlab platform
Matthew John Smalley - One of the best experts on this subject based on the ideXlab platform.
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dissociation of estrogen receptor expression and in vivo stem cell activity in the mammary gland
Journal of Cell Biology, 2007Co-Authors: Katherine E Sleeman, Howard Kendrick, David Robertson, Clare M Isacke, Alan Ashworth, Matthew John SmalleyAbstract:The role of estrogen in promoting mammary stem cell proliferation remains controversial. It is unclear if estrogen receptor (ER)–expressing cells have stem/progenitor activity themselves or if they act in a paracrine fashion to stimulate stem cell proliferation. We have used flow cytometry to prospectively isolate mouse mammary ER-expressing epithelial cells and shown, using analysis of gene expression patterns and cell type–specific markers, that they form a distinct luminal epithelial cell subpopulation that expresses not only the ER but also the progesterone and Prolactin Receptors. Furthermore, we have used an in vivo functional transplantation assay to directly demonstrate that the ER-expressing luminal epithelial subpopulation contains little in vivo stem cell activity. Rather, the mammary stem cell activity is found within the basal mammary epithelial cell population. Therefore, ER-expressing cells of the mammary epithelium are distinct from the mammary stem cell population, and the effects of estrogen on mammary stem cells are likely to be mediated indirectly. These results are important for our understanding of cellular responses to hormonal stimulation in the normal breast and in breast cancer.
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dissociation of estrogen receptor expression and in vivo stem cell activity in the mammary gland
Journal of Cell Biology, 2007Co-Authors: Katherine E Sleeman, Howard Kendrick, David Robertson, Clare M Isacke, Alan Ashworth, Matthew John SmalleyAbstract:The role of estrogen in promoting mammary stem cell proliferation remains controversial. It is unclear if estrogen receptor (ER)–expressing cells have stem/progenitor activity themselves or if they act in a paracrine fashion to stimulate stem cell proliferation. We have used flow cytometry to prospectively isolate mouse mammary ER-expressing epithelial cells and shown, using analysis of gene expression patterns and cell type–specific markers, that they form a distinct luminal epithelial cell subpopulation that expresses not only the ER but also the progesterone and Prolactin Receptors. Furthermore, we have used an in vivo functional transplantation assay to directly demonstrate that the ER-expressing luminal epithelial subpopulation contains little in vivo stem cell activity. Rather, the mammary stem cell activity is found within the basal mammary epithelial cell population. Therefore, ER-expressing cells of the mammary epithelium are distinct from the mammary stem cell population, and the effects of estrogen on mammary stem cells are likely to be mediated indirectly. These results are important for our understanding of cellular responses to hormonal stimulation in the normal breast and in breast cancer.
David R Grattan - One of the best experts on this subject based on the ideXlab platform.
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Prolactin Receptors in rip cre cells but not in agrp neurones are involved in energy homeostasis
Journal of Neuroendocrinology, 2017Co-Authors: Sharon R Ladyman, M A Macleod, Khant Z Aung, Penelope J Knowles, Hollian R Phillipps, Rosemary S E Brown, David R GrattanAbstract: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 (Prlrlox/lox mice). The Prlrlox/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, Prlrlox/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 responsive to Prolactin and may play a role in the orexigenic effects of Prolactin, whereas Prolactin does not directly affect Agrp neurones.
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expression of the long form of the Prolactin receptor in magnocellular oxytocin neurons is associated with specific Prolactin regulation of oxytocin neurons
American Journal of Physiology-regulatory Integrative and Comparative Physiology, 2006Co-Authors: Ilona C Kokay, Philip M Bull, R L Davis, Mike Ludwig, David R GrattanAbstract:Magnocellular neurons of the supraoptic (SON) and paraventricular nuclei (PVN) show considerable plasticity during pregnancy and lactation. Prolactin Receptors (PRL-R) have been identified in both these nuclei. The aim of this study was to investigate the cell type(s) expressing mRNA for the long form of Prolactin receptor (PRL-RL) and to determine whether patterns of expression change during pregnancy and lactation. In addition, we examined effects of Prolactin on excitability of oxytocin and vasopressin neurons. Sections from brains of nonpregnant, pregnant, and lactating rats were hybridized with an 35S-labeled probe to label PRL-RL mRNA together with digoxigenin-labeled probes to detect either oxytocin or vasopressin mRNA. In the SON, PRL-RL mRNA was predominantly colocalized with oxytocin mRNA, with over 80% of oxytocin neurons positive for PRL-RL mRNA. Very few (<10%) vasopressin neurons expressed PRL-RL mRNA. In the PVN, PRL-RL mRNA was also predominantly found in oxytocin neurons, and the proporti...
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Prolactin Receptors in the brain during pregnancy and lactation implications for behavior
Hormones and Behavior, 2001Co-Authors: David R Grattan, Zane B Andrews, Rachael A Augustine, Ilona C Kokay, M R Summerfield, B Todd, Stephen J BunnAbstract:Numerous studies have documented Prolactin regulation of a variety of brain functions, including maternal behavior, regulation of oxytocin neurons, regulation of feeding and appetite, suppression of ACTH secretion in response to stress, and suppression of fertility. We have observed marked changes in expression of Prolactin Receptors in specific hypothalamic nuclei during pregnancy and lactation. This has important implications for neuronal functions regulated by Prolactin. In light of the high circulating levels of Prolactin during pregnancy and lactation and the increased expression of Prolactin Receptors in the hypothalamus, many of these functions may be enhanced or exaggerated in the maternal brain. The adaptations of the maternal brain allow the female to exhibit the appropriate behavior to feed and nurture her offspring, to adjust to the nutritional and metabolic demands of milk production, and to maintain appropriate hormone secretion to allow milk synthesis, secretion, and ejection. This review aims to summarize the evidence that Prolactin plays a key role in regulating hypothalamic function during lactation and to discuss the hypothesis that the overall role of Prolactin is to organize and coordinate this wide range of behavioral and neuroendocrine adaptations during pregnancy and lactation.
Katherine E Sleeman - One of the best experts on this subject based on the ideXlab platform.
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dissociation of estrogen receptor expression and in vivo stem cell activity in the mammary gland
Journal of Cell Biology, 2007Co-Authors: Katherine E Sleeman, Howard Kendrick, David Robertson, Clare M Isacke, Alan Ashworth, Matthew John SmalleyAbstract:The role of estrogen in promoting mammary stem cell proliferation remains controversial. It is unclear if estrogen receptor (ER)–expressing cells have stem/progenitor activity themselves or if they act in a paracrine fashion to stimulate stem cell proliferation. We have used flow cytometry to prospectively isolate mouse mammary ER-expressing epithelial cells and shown, using analysis of gene expression patterns and cell type–specific markers, that they form a distinct luminal epithelial cell subpopulation that expresses not only the ER but also the progesterone and Prolactin Receptors. Furthermore, we have used an in vivo functional transplantation assay to directly demonstrate that the ER-expressing luminal epithelial subpopulation contains little in vivo stem cell activity. Rather, the mammary stem cell activity is found within the basal mammary epithelial cell population. Therefore, ER-expressing cells of the mammary epithelium are distinct from the mammary stem cell population, and the effects of estrogen on mammary stem cells are likely to be mediated indirectly. These results are important for our understanding of cellular responses to hormonal stimulation in the normal breast and in breast cancer.
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dissociation of estrogen receptor expression and in vivo stem cell activity in the mammary gland
Journal of Cell Biology, 2007Co-Authors: Katherine E Sleeman, Howard Kendrick, David Robertson, Clare M Isacke, Alan Ashworth, Matthew John SmalleyAbstract:The role of estrogen in promoting mammary stem cell proliferation remains controversial. It is unclear if estrogen receptor (ER)–expressing cells have stem/progenitor activity themselves or if they act in a paracrine fashion to stimulate stem cell proliferation. We have used flow cytometry to prospectively isolate mouse mammary ER-expressing epithelial cells and shown, using analysis of gene expression patterns and cell type–specific markers, that they form a distinct luminal epithelial cell subpopulation that expresses not only the ER but also the progesterone and Prolactin Receptors. Furthermore, we have used an in vivo functional transplantation assay to directly demonstrate that the ER-expressing luminal epithelial subpopulation contains little in vivo stem cell activity. Rather, the mammary stem cell activity is found within the basal mammary epithelial cell population. Therefore, ER-expressing cells of the mammary epithelium are distinct from the mammary stem cell population, and the effects of estrogen on mammary stem cells are likely to be mediated indirectly. These results are important for our understanding of cellular responses to hormonal stimulation in the normal breast and in breast cancer.
Nadine Binart - One of the best experts on this subject based on the ideXlab platform.
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RESEARCH ARTICLE Prolactin Receptors and Placental Lactogen Drive Male Mouse Pancreatic Islets to Pregnancy-Related mRNA Changes
2016Co-Authors: Lotte Goyvaerts, Nadine Binart, Katleen Lemaire, Ingrid Arijs, Julien Auffret, Mikaela Granvik, Leentje Van Lommel, Frans Schuit, Peter In’t Veld, Anica SchraenenAbstract:Pregnancy requires a higher functional beta cell mass and this is associated with profound changes in the gene expression profile of pancreatic islets. Taking Tph1 as a sensitive marker for pregnancy-related islet mRNA expression in female mice, we previously identi-fied Prolactin Receptors and placental lactogen as key signalling molecules. Since beta cells from male mice also express Prolactin Receptors, the question arose whether male and fe-male islets have the same phenotypic resilience at the mRNA level during pregnancy. We addressed this question in vitro, by stimulating cultured islets with placental lactogen and in vivo, by transplanting male or female islets into female acceptor mice. Additionally, the islet mRNA expression pattern of pregnant Prolactin receptor deficient mice was compared with that of their pregnant wild-type littermates. When cultured with placental lactogen, or when transplanted in female recipients that became pregnant (day 12.5), male islets in-duced the ‘islet pregnancy gene signature’, which we defined as the 12 highest induced genes in non-transplanted female islets at day 12.5 of pregnancy. In addition, serotonin immunoreactivity and beta cell proliferation was also induced in these male transplanted is
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Prolactin Receptors and placental lactogen drive male mouse pancreatic islets to pregnancy related mrna changes
PLOS ONE, 2015Co-Authors: Lotte Goyvaerts, Nadine Binart, Katleen Lemaire, Ingrid Arijs, Julien Auffret, Mikaela Granvik, Leentje Van Lommel, Peter Int Veld, Frans Schuit, Anica SchraenenAbstract:Pregnancy requires a higher functional beta cell mass and this is associated with profound changes in the gene expression profile of pancreatic islets. Taking Tph1 as a sensitive marker for pregnancy-related islet mRNA expression in female mice, we previously identified Prolactin Receptors and placental lactogen as key signalling molecules. Since beta cells from male mice also express Prolactin Receptors, the question arose whether male and female islets have the same phenotypic resilience at the mRNA level during pregnancy. We addressed this question in vitro, by stimulating cultured islets with placental lactogen and in vivo, by transplanting male or female islets into female acceptor mice. Additionally, the islet mRNA expression pattern of pregnant Prolactin receptor deficient mice was compared with that of their pregnant wild-type littermates. When cultured with placental lactogen, or when transplanted in female recipients that became pregnant (day 12.5), male islets induced the ‘islet pregnancy gene signature’, which we defined as the 12 highest induced genes in non-transplanted female islets at day 12.5 of pregnancy. In addition, serotonin immunoreactivity and beta cell proliferation was also induced in these male transplanted islets at day 12.5 of pregnancy. In order to further investigate the importance of Prolactin Receptors in these mRNA changes we used a Prolactin receptor deficient mouse model. For the 12 genes of the signature, which are highly induced in control pregnant mice, no significant induction of mRNA transcripts was found at day 9.5 of pregnancy. Together, our results support the key role of placental lactogen as a circulating factor that can trigger the pregnancy mRNA profile in both male and female beta cells.
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the hormone Prolactin is a novel endogenous trophic factor able to regulate reactive glia and to limit retinal degeneration
The Journal of Neuroscience, 2014Co-Authors: Edith Arnold, German D Baezacruz, Gerardo Rojaspiloni, Andres Quintanarstephano, David Arredondo Zamarripa, Norma Adan, Miguel Condeslara, Stéphanie Thebault, Nadine Binart, Gonzalo Martínez De La EscaleraAbstract: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.
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hyperProlactinemia induced ovarian acyclicity is reversed by kisspeptin administration
Journal of Clinical Investigation, 2012Co-Authors: Charlotte Sonigo, Justine Bouilly, Virginie Tolle, Alain Caraty, Fabianjesus Simonyconesa, Javier A Tello, Robert P. Millar, Jacques Young, Nadege Carre, Nadine BinartAbstract:HyperProlactinemia is the most common cause of hypogonadotropic anovulation and is one of the leading causes of infertility in women aged 25–34. HyperProlactinemia has been proposed to block ovulation through inhibition of GnRH release. Kisspeptin neurons, which express Prolactin Receptors, were recently identified as major regulators of GnRH neurons. To mimic the human pathology of anovulation, we continuously infused female mice with Prolactin. Our studies demonstrated that hyperProlactinemia in mice induced anovulation, reduced GnRH and gonadotropin secretion, and diminished kisspeptin expression. Kisspeptin administration restored gonadotropin secretion and ovarian cyclicity, suggesting that kisspeptin neurons play a major role in hyperProlactinemic anovulation. Our studies indicate that administration of kisspeptin may serve as an alternative therapeutic approach to restore the fertility of hyperProlactinemic women who are resistant or intolerant to dopamine agonists.
Lotte Goyvaerts - One of the best experts on this subject based on the ideXlab platform.
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RESEARCH ARTICLE Prolactin Receptors and Placental Lactogen Drive Male Mouse Pancreatic Islets to Pregnancy-Related mRNA Changes
2016Co-Authors: Lotte Goyvaerts, Nadine Binart, Katleen Lemaire, Ingrid Arijs, Julien Auffret, Mikaela Granvik, Leentje Van Lommel, Frans Schuit, Peter In’t Veld, Anica SchraenenAbstract:Pregnancy requires a higher functional beta cell mass and this is associated with profound changes in the gene expression profile of pancreatic islets. Taking Tph1 as a sensitive marker for pregnancy-related islet mRNA expression in female mice, we previously identi-fied Prolactin Receptors and placental lactogen as key signalling molecules. Since beta cells from male mice also express Prolactin Receptors, the question arose whether male and fe-male islets have the same phenotypic resilience at the mRNA level during pregnancy. We addressed this question in vitro, by stimulating cultured islets with placental lactogen and in vivo, by transplanting male or female islets into female acceptor mice. Additionally, the islet mRNA expression pattern of pregnant Prolactin receptor deficient mice was compared with that of their pregnant wild-type littermates. When cultured with placental lactogen, or when transplanted in female recipients that became pregnant (day 12.5), male islets in-duced the ‘islet pregnancy gene signature’, which we defined as the 12 highest induced genes in non-transplanted female islets at day 12.5 of pregnancy. In addition, serotonin immunoreactivity and beta cell proliferation was also induced in these male transplanted is
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Prolactin Receptors and placental lactogen drive male mouse pancreatic islets to pregnancy related mrna changes
PLOS ONE, 2015Co-Authors: Lotte Goyvaerts, Nadine Binart, Katleen Lemaire, Ingrid Arijs, Julien Auffret, Mikaela Granvik, Leentje Van Lommel, Peter Int Veld, Frans Schuit, Anica SchraenenAbstract:Pregnancy requires a higher functional beta cell mass and this is associated with profound changes in the gene expression profile of pancreatic islets. Taking Tph1 as a sensitive marker for pregnancy-related islet mRNA expression in female mice, we previously identified Prolactin Receptors and placental lactogen as key signalling molecules. Since beta cells from male mice also express Prolactin Receptors, the question arose whether male and female islets have the same phenotypic resilience at the mRNA level during pregnancy. We addressed this question in vitro, by stimulating cultured islets with placental lactogen and in vivo, by transplanting male or female islets into female acceptor mice. Additionally, the islet mRNA expression pattern of pregnant Prolactin receptor deficient mice was compared with that of their pregnant wild-type littermates. When cultured with placental lactogen, or when transplanted in female recipients that became pregnant (day 12.5), male islets induced the ‘islet pregnancy gene signature’, which we defined as the 12 highest induced genes in non-transplanted female islets at day 12.5 of pregnancy. In addition, serotonin immunoreactivity and beta cell proliferation was also induced in these male transplanted islets at day 12.5 of pregnancy. In order to further investigate the importance of Prolactin Receptors in these mRNA changes we used a Prolactin receptor deficient mouse model. For the 12 genes of the signature, which are highly induced in control pregnant mice, no significant induction of mRNA transcripts was found at day 9.5 of pregnancy. Together, our results support the key role of placental lactogen as a circulating factor that can trigger the pregnancy mRNA profile in both male and female beta cells.
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impaired islet function in commonly used transgenic mouse lines due to human growth hormone minigene expression
Cell Metabolism, 2014Co-Authors: Bas Brouwers, Lotte Goyvaerts, Katleen Lemaire, Mikaela Granvik, Geoffroy De Faudeur, Anna B Osipovich, Leen Boesmans, Elisa J G Cauwelier, Vincent P E G Pruniau, Leentje Van LommelAbstract:Summary The human growth hormone ( hGH ) minigene is frequently used in the derivation of transgenic mouse lines to enhance transgene expression. Although this minigene is present in the transgenes as a secondcistron, and thus not thought to be expressed, we found that three commonly used lines, Pdx1-Cre Late , RIP-Cre , and MIP-GFP , each expressed significant amounts of hGH in pancreatic islets. Locally secreted hGH binds to Prolactin Receptors on β cells, activates STAT5 signaling, and induces pregnancy-like changes in gene expression, thereby augmenting pancreatic β cell mass and insulin content. In addition, islets of Pdx1-Cre Late mice have lower GLUT2 expression and reduced glucose-induced insulin release and are protected against the β cell toxin streptozotocin. These findings may be important when interpreting results obtained when these and other hGH minigene-containing transgenic mice are used.
