The Experts below are selected from a list of 42228 Experts worldwide ranked by ideXlab platform
Marc E Freeman - One of the best experts on this subject based on the ideXlab platform.
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nuclear translocation of stat5 and increased expression of fos related antigens fras in hypothalamic dopaminergic neurons after Prolactin administration
Brain Research, 2001Co-Authors: Anna Lerant, Bela Kanyicska, Marc E FreemanAbstract:Ample evidence indicates feedback relationships between pituitary Prolactin and hypothalamic dopaminergic neurons. Since the presence of Prolactin receptors was earlier demonstrated in hypothalamic dopaminergic neurons, our working hypothesis was that Prolactin induced activation of Prolactin receptor coupled signaling leads to increased neuronal activity in these neurons. The aim of this study was to correlate Prolactin receptor mediated signaling and Prolactin induced activation in hypothalamic dopaminergic neurons. We used nuclear translocation of STAT5 as a marker of Prolactin receptor induced signaling and expression of Fos related antigens (FRAs) as an indicator of neuronal activation. We performed double label immunocytochemical studies to determine the time course of the presence of FRAs and STAT5 in the nuclei of hypothalamic dopaminergic neurons after ovine Prolactin treatment. Exogenous ovine Prolactin treatment of ovariectomized rats resulted in an increase in serum ovine Prolactin levels and a decrease in endogenous serum Prolactin levels, indicating that ovine Prolactin activated mechanisms inhibited pituitary Prolactin secretion. Indeed, ovine Prolactin activated the Prolactin receptors in most subpopulations of hypothalamic dopaminergic neurons, resulting in nuclear translocation of STAT5. Also, increased neuronal activity, indicated by expression of FRAs, was observed in the same neuron populations after ovine Prolactin treatment. These results suggest that signal transduction mechanisms coupled to Prolactin receptors in hypothalamic dopaminergic neurons resemble those observed in other tissues; and nuclear translocation of STAT5 can be used as a marker of Prolactin receptor activation in hypothalamic dopaminergic neurons.
David R Grattan - One of the best experts on this subject based on the ideXlab platform.
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Elevated Prolactin during Pregnancy Drives a Phenotypic Switch in Mouse Hypothalamic Dopaminergic Neurons
Elsevier, 2019Co-Authors: Siew H. Yip, David R Grattan, Nicola Romanò, Papillon Gustafson, David J. Hodson, Eloise J. Williams, Ilona C. Kokay, Agnes O. Martin, Patrice Mollard, Stephen J. BunnAbstract:Summary: Altered physiological states require neuronal adaptation. In late pregnancy and lactation, a sub-population of the mouse hypothalamic tuberoinfundibular dopaminergic (TIDA) neurons alters their behavior to synthesize and release met-enkephalin rather than dopamine. These neurons normally release dopamine to inhibit Prolactin secretion and are activated by Prolactin in a short-loop feedback manner. In lactation, dopamine synthesis is suppressed in an opioid-dependent (naloxone-reversible) manner, meaning that Prolactin secretion is disinhibited. Conditional deletion of the Prolactin receptor in neurons reveals that this change in phenotype appears to be driven by Prolactin itself, apparently through an alteration in intracellular signaling downstream of the Prolactin receptor that favors enkephalin production instead of dopamine. Thus, Prolactin effectively facilitates its own secretion, which is essential for lactation and maternal behavior. These studies provide evidence of a physiologically important, reversible alteration in the behavior of a specific population of hypothalamic neurons in the adult brain. : Pituitary Prolactin secretion is inhibited by dopamine released by hypothalamic neurons. Yip et al. show that, during lactation, these TIDA neurons alter their response to Prolactin and release enkephalin in place of dopamine. This mechanism promotes rather than inhibits Prolactin secretion, supporting its elevation during lactation. Keywords: Prolactin, Prolactin receptor, dopamine, encephalin, hypothalamus, tuberoinfundibular dopaminergic neurons, neuronal plasticity, lactation, lactotroph
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restraint stress increases Prolactin mediated phosphorylation of signal transducer and activator of transcription 5 in the hypothalamus and adrenal cortex in the male mouse
Journal of Neuroendocrinology, 2017Co-Authors: Siobhan E Kirk, David R Grattan, T Y Xie, Frederik J Steyn, Stephen J. BunnAbstract:Prolactin is a pleiotropic peptide hormone produced by the lactotrophs in the anterior pituitary. Its rate of secretion is primarily regulated by a negative-feedback mechanism where Prolactin stimulates the activity of the tuberoinfundibular dopaminergic (TIDA) neurones, increasing their release of dopamine, which accesses the pituitary via the median eminence to suppress further Prolactin secretion. In addition to its well established role in lactation, circulating Prolactin is secreted in response to stress, although the mechanism by which this is achieved or its cellular targets remains unknown. In the present study, we show that 15 minutes of restraint stress causes an approximately seven-fold increase in circulating Prolactin concentration in male mice. Monitoring Prolactin receptor activation, using immunohistochemistry to determine the level and distribution of tyrosine phosphorylated signal transducer and activator of transcription 5 (pSTAT5), we show that this stress-induced increase in Prolactin interacts with both central and peripheral targets. Restraint stress for 15 minutes significantly increased pSTAT5 staining in the arcuate nucleus, median eminence and the zona fasciculata of the adrenal cortex. In each case, this response was prevented by pretreating the animals with bromocriptine to block Prolactin secretion from the pituitary. Interestingly, in contrast to many cells in the arcuate nucleus, stress reduced pSTAT5 staining of the TIDA neurones (identified by dual-labelling for tyrosine hydroxylase). This suggests that there is reduced Prolactin signalling in these cells and thus potentially a decline in their inhibitory influence on Prolactin secretion. These results provide evidence that Prolactin secreted in response to acute stress is sufficient to activate Prolactin receptors in selected target tissues known to be involved in the physiological adaptation to stress.
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60 years of neuroendocrinology the hypothalamo Prolactin axis
Journal of Endocrinology, 2015Co-Authors: David R GrattanAbstract:The hypothalamic control of Prolactin secretion is different from other anterior pituitary hormones, in that it is predominantly inhibitory, by means of dopamine from the tuberoinfundibular dopamine neurons. In addition, Prolactin does not have an endocrine target tissue, and therefore lacks the classical feedback pathway to regulate its secretion. Instead, it is regulated by short loop feedback, whereby Prolactin itself acts in the brain to stimulate production of dopamine and thereby inhibit its own secretion. Finally, despite its relatively simple name, Prolactin has a broad range of functions in the body, in addition to its defining role in promoting lactation. As such, the hypothalamo-Prolactin axis has many characteristics that are quite distinct from other hypothalamo-pituitary systems. This review will provide a brief overview of our current understanding of the neuroendocrine control of Prolactin secretion, in particular focusing on the plasticity evident in this system, which keeps Prolactin secretion at low levels most of the time, but enables extended periods of hyperProlactinemia when necessary for lactation. Key Prolactin functions beyond milk production will be discussed, particularly focusing on the role of Prolactin in inducing adaptive responses in multiple different systems to facilitate lactation, and the consequences if Prolactin action is impaired. A feature of this pleiotropic activity is that functions that may be adaptive in the lactating state might be maladaptive if Prolactin levels are elevated inappropriately. Overall, my goal is to give a flavour of both the history and current state of the field of Prolactin neuroendocrinology, and identify some exciting new areas of research development.
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reproductive experience increases Prolactin responsiveness in the medial preoptic area and arcuate nucleus of female rats
Endocrinology, 2006Co-Authors: Greg M Anderson, David R Grattan, Willemijn Van Den Ancker, Robert S BridgesAbstract:The experience of pregnancy plus lactation produces longterm enhancements in maternal behavior as well as reduced secretion of Prolactin, a key hormone for the initial establishment of maternal care. Given that Prolactin acts centrally to induce maternal care as well as regulate its own secretion, we tested whether Prolactin receptors in brain regions known to regulate behavioral and neuroendocrine processes were upregulated and more responsive to Prolactin in reproductively experiencedfemales.Diestrousprimiparous(8wkafterweaning) and age-matched virgin rats were treated with 250 g ovine Prolactin sc or vehicle and the brains collected 2 h later for measurement of mRNA for genes involved in Prolactin signaling. Reproductively experienced rats had lower serum Prolactin concentrations, compared with virgin rats, suggesting enhanced Prolactin feedback on the arcuate neurons regulating Prolactin secretion. In the medial preoptic area and arcuate nucleus (regions involved in regulating maternal behavior and Prolactin secretion, respectively), the level of long-form Prolactin receptor mRNA was higher in primiparous rats, and Prolactin treatment induced a further increase in receptor expression in these animals. In the same regions, suppressors of cytokine signaling-1 and -3 mRNA levels were also markedly increased after Prolactin treatment in reproductively experienced but not virgin rats. These results support the idea that reproductive experience increases central Prolactin responsiveness. The induction of Prolactin receptors and enhanced Prolactin responsivenessasaresultofpregnancyandlactationmayhelpaccount for the retention of maternal behavior and shifts in Prolactin secretion in reproductively experienced females. (Endocrinology 147: 4688–4694, 2006)
Hallgeir Rui - One of the best experts on this subject based on the ideXlab platform.
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insensitivity of human Prolactin receptors to nonhuman Prolactins relevance for experimental modeling of Prolactin receptor expressing human cells
Endocrinology, 2009Co-Authors: Fransiscus E Utama, Matthew J Lebaron, Thai H Tran, Amy Ryder, Albert F Parlow, Hallgeir RuiAbstract:Prolactin (PRL) receptors are expressed in a broad range of human cell types and in a majority of human breast and prostate cancers. Experimentally, normal and malignant human cells are typically cultured in vitro in media containing bovine PRL (bPRL) from fetal bovine serum or as xenotransplants in vivo in the presence of murine PRL (mPRL). The biological efficacy of bPRL toward hPRL receptors (hPRLR) is controversial, and hPRLR are insensitive to mPRL, but the mechanism is not known. To clarify limitations of current in vitro and in vivo experimental model systems for studies of hPRLR-expressing cells, we tested human and relevant subprimate Prolactins in multiple hPRLR bioassays. bPRL and ovine PRL were 10-fold less potent hPRLR agonists than hPRL, although maximal responses at high ligand concentrations (efficacies) equaled that of hPRL. mPRL and rat PRL had greater than 50-fold lower potencies toward hPRLR than hPRL and had 50% reduced efficacies. In fact, mPRL and rat PRL were less effective hPRLR agonists than murine GH. Unexpectedly, mPRL was an effective competitive inhibitor of hPRL binding to hPRLR with an inhibitory constant of 1.3 nm and showed partial antagonist activity, suggesting reduced site-2 binding. Collectively, low bioactivities of bPRL and mPRL toward hPRLR suggest that existing laboratory cancer cell lines grown in 10% bovine serum-supplemented media or in mice are selected for growth under lactogen-depleted conditions. The biology and drug responsiveness of existing human cell lines may therefore not be representative of clinical cancers that are sensitive to circulating PRL.
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human Prolactin receptors are insensitive to mouse Prolactin implications for xenotransplant modeling of human breast cancer in mice
Journal of Endocrinology, 2006Co-Authors: Fransiscus E Utama, Matthew J Lebaron, L M Neilson, A S Sultan, A F Parlow, Kay Uwe Wagner, Hallgeir RuiAbstract:Experimental testing of growth, metastatic progression and drug responsiveness of human breast cancer in vivo is performed in immunodeficient mice. Drug candidates need to show promise against human breast cancer in mice before being allowed into clinical trials. Breast cancer growth is under endocrine control by ovarian steroids and the pituitary peptide hormone Prolactin. While it is recognized that the most relevant biologic effects of Prolactin are achieved with Prolactin from the matching species, the biologic efficacy of mouse Prolactin for human Prolactin receptors has not been recorded. Thus, it is unclear whether the mouse endocrine environment adequately reflects the hormonal environment in breast cancer patients with regard to Prolactin. We now show both recombinant and natural pituitary-derived mouse Prolactin to be a poor agonist for human Prolactin receptors. Mouse Prolactin failed to induce human Prolactin receptor-mediated biologic responses of cell clustering, proliferation, gene induction and signal transduction, including activation of Stat5, Stat3, Erk1/2 and Akt pathways. Consistent data were derived from human breast cancer lines T-47D, MCF-7 and ZR-75.1, as well as human Prolactin receptor-transfected COS-7 and 32D cells. Failure of mouse Prolactin to activate human Prolactin receptors uncovers a key deficiency of the mouse endocrine environment for human xenotransplant studies. Since most human breast cancers express Prolactin receptors, human breast cancer transferred into mice is unnaturally selected for growth in the absence of circulating Prolactin. The new insight raises concerns about the validity of analyzing biology and drug responsiveness of human breast cancer in existing mouse xenotransplant models.
Stephen J. Bunn - One of the best experts on this subject based on the ideXlab platform.
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Elevated Prolactin during Pregnancy Drives a Phenotypic Switch in Mouse Hypothalamic Dopaminergic Neurons
Elsevier, 2019Co-Authors: Siew H. Yip, David R Grattan, Nicola Romanò, Papillon Gustafson, David J. Hodson, Eloise J. Williams, Ilona C. Kokay, Agnes O. Martin, Patrice Mollard, Stephen J. BunnAbstract:Summary: Altered physiological states require neuronal adaptation. In late pregnancy and lactation, a sub-population of the mouse hypothalamic tuberoinfundibular dopaminergic (TIDA) neurons alters their behavior to synthesize and release met-enkephalin rather than dopamine. These neurons normally release dopamine to inhibit Prolactin secretion and are activated by Prolactin in a short-loop feedback manner. In lactation, dopamine synthesis is suppressed in an opioid-dependent (naloxone-reversible) manner, meaning that Prolactin secretion is disinhibited. Conditional deletion of the Prolactin receptor in neurons reveals that this change in phenotype appears to be driven by Prolactin itself, apparently through an alteration in intracellular signaling downstream of the Prolactin receptor that favors enkephalin production instead of dopamine. Thus, Prolactin effectively facilitates its own secretion, which is essential for lactation and maternal behavior. These studies provide evidence of a physiologically important, reversible alteration in the behavior of a specific population of hypothalamic neurons in the adult brain. : Pituitary Prolactin secretion is inhibited by dopamine released by hypothalamic neurons. Yip et al. show that, during lactation, these TIDA neurons alter their response to Prolactin and release enkephalin in place of dopamine. This mechanism promotes rather than inhibits Prolactin secretion, supporting its elevation during lactation. Keywords: Prolactin, Prolactin receptor, dopamine, encephalin, hypothalamus, tuberoinfundibular dopaminergic neurons, neuronal plasticity, lactation, lactotroph
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restraint stress increases Prolactin mediated phosphorylation of signal transducer and activator of transcription 5 in the hypothalamus and adrenal cortex in the male mouse
Journal of Neuroendocrinology, 2017Co-Authors: Siobhan E Kirk, David R Grattan, T Y Xie, Frederik J Steyn, Stephen J. BunnAbstract:Prolactin is a pleiotropic peptide hormone produced by the lactotrophs in the anterior pituitary. Its rate of secretion is primarily regulated by a negative-feedback mechanism where Prolactin stimulates the activity of the tuberoinfundibular dopaminergic (TIDA) neurones, increasing their release of dopamine, which accesses the pituitary via the median eminence to suppress further Prolactin secretion. In addition to its well established role in lactation, circulating Prolactin is secreted in response to stress, although the mechanism by which this is achieved or its cellular targets remains unknown. In the present study, we show that 15 minutes of restraint stress causes an approximately seven-fold increase in circulating Prolactin concentration in male mice. Monitoring Prolactin receptor activation, using immunohistochemistry to determine the level and distribution of tyrosine phosphorylated signal transducer and activator of transcription 5 (pSTAT5), we show that this stress-induced increase in Prolactin interacts with both central and peripheral targets. Restraint stress for 15 minutes significantly increased pSTAT5 staining in the arcuate nucleus, median eminence and the zona fasciculata of the adrenal cortex. In each case, this response was prevented by pretreating the animals with bromocriptine to block Prolactin secretion from the pituitary. Interestingly, in contrast to many cells in the arcuate nucleus, stress reduced pSTAT5 staining of the TIDA neurones (identified by dual-labelling for tyrosine hydroxylase). This suggests that there is reduced Prolactin signalling in these cells and thus potentially a decline in their inhibitory influence on Prolactin secretion. These results provide evidence that Prolactin secreted in response to acute stress is sufficient to activate Prolactin receptors in selected target tissues known to be involved in the physiological adaptation to stress.
Anna Lerant - One of the best experts on this subject based on the ideXlab platform.
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nuclear translocation of stat5 and increased expression of fos related antigens fras in hypothalamic dopaminergic neurons after Prolactin administration
Brain Research, 2001Co-Authors: Anna Lerant, Bela Kanyicska, Marc E FreemanAbstract:Ample evidence indicates feedback relationships between pituitary Prolactin and hypothalamic dopaminergic neurons. Since the presence of Prolactin receptors was earlier demonstrated in hypothalamic dopaminergic neurons, our working hypothesis was that Prolactin induced activation of Prolactin receptor coupled signaling leads to increased neuronal activity in these neurons. The aim of this study was to correlate Prolactin receptor mediated signaling and Prolactin induced activation in hypothalamic dopaminergic neurons. We used nuclear translocation of STAT5 as a marker of Prolactin receptor induced signaling and expression of Fos related antigens (FRAs) as an indicator of neuronal activation. We performed double label immunocytochemical studies to determine the time course of the presence of FRAs and STAT5 in the nuclei of hypothalamic dopaminergic neurons after ovine Prolactin treatment. Exogenous ovine Prolactin treatment of ovariectomized rats resulted in an increase in serum ovine Prolactin levels and a decrease in endogenous serum Prolactin levels, indicating that ovine Prolactin activated mechanisms inhibited pituitary Prolactin secretion. Indeed, ovine Prolactin activated the Prolactin receptors in most subpopulations of hypothalamic dopaminergic neurons, resulting in nuclear translocation of STAT5. Also, increased neuronal activity, indicated by expression of FRAs, was observed in the same neuron populations after ovine Prolactin treatment. These results suggest that signal transduction mechanisms coupled to Prolactin receptors in hypothalamic dopaminergic neurons resemble those observed in other tissues; and nuclear translocation of STAT5 can be used as a marker of Prolactin receptor activation in hypothalamic dopaminergic neurons.
