Sylvie Thirion

Sylvie Thirion
Aix-Marseille Université | AMU · Centre de Recherche en Neurobiologie-Neurophysiologie de Marseille (UMR 7286 CRN2M)

PhD

About

55
Publications
7,258
Reads
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2,137
Citations
Additional affiliations
September 2003 - present
Aix-Marseille Université
Position
  • Professor (Assistant)
September 2003 - August 2006
French National Centre for Scientific Research
Position
  • Researcher

Publications

Publications (55)
Article
Full-text available
Context: The ghrelin receptor GHS-R1a is highly expressed in human somatotroph adenomas and exhibits unusually high basal signaling activity. In humans, the suppression of this constitutive activity by mutation induces a short stature. Objective: Using a GHS-R1a inverse agonist, modified substance P (MSP), we explored the role of GHS-R1a constit...
Article
Full-text available
Abundant evidences have shown that ghrelin, by its binding to GHS-R1a, plays an important role for fundamental physiological functions. Increasing attention is given to the GHS-R1a unusually high constitutive activity and its contribution to downstream signaling and physiological processes. Here, we review recent lines of evidences showing that the...
Article
Full-text available
Pituitary tumors are most usual intracranial tumors, displaying hormonal hyper-secretion with in some cases a sustained cell proliferation. The somatotroph adenomas are characterised by a GH hypersecretion. The current treatments are based on somatostatinergic or dopaminergic agonists. Unfortunately, there is steel 50% of patients, which remain ins...
Article
Full-text available
Somatostatin is a ubiquitous neuropeptidic inhibitor of various cellular functions including endocrine and exocrine secretion. Moreover, this peptide may control cell proliferation in normal and tumoral tissues. Somatostatin biological effects are mediated by five subtype of G protein-coupled receptor, sst1 through sst5. The somatostatin analogs ha...
Article
The Ras/Raf/MEK/ERK is a conserved signalling pathway involved in the control of fundamental cellular processes. Despite extensive research, how this pathway can process a myriad of diverse extracellular inputs into substrate specificity to determine biological outcomes is not fully understood. It has been established that the ERK1/2 pathway is an...
Article
Full-text available
Physiological regulations of energy balance and body weight imply highly adaptive mechanisms which match caloric intake to caloric expenditure. In the central nervous system, the regulation of appetite relies on complex neurocircuitry which disturbance may alter energy balance and result in anorexia or obesity. Deoxynivalenol (DON), a trichothecene...
Article
Full-text available
The treatment of growth hormone (GH)- and prolactin (PRL)-secreting tumors resistant to current therapeutic molecules (somatostatin and dopamine analogues) remains challenging. To target these tumors specifically, we chose to inactivate a gene coding for a crucial factor in cell proliferation and hormonal regulation, specifically expressed in pitui...
Article
Full-text available
Deoxynivalenol (DON), one of the most abundant trichothecenes found on cereals, has been implicated in mycotoxicoses in both humans and farm animals. Low-dose toxicity is characterized by reduced weight gain, diminished nutritional efficiency, and immunologic effects. The levels and patterns of human food commodity contamination justify that DON co...
Article
Full-text available
Nonfunctioning pituitary adenomas (NFPA; gonadotroph derived), even not inducing hormonal hypersecretion, cause significant morbidity by compression neighboring structures. No effective and specific medical methods are available so far for treating these tumors. The pituitary homeobox 2 (PITX2) gene is a member of the bicoid-like homeobox transcrip...
Article
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For decades, the struggle against inflammation and related disorders has constituted an important field in medical practice, with strategies mainly aimed to inhibit the compounds produced through the arachidonic acid pathway. Thus, specific COX-2 inhibitors or “coxibs”, have been recently designed that play an important but controversial role in re...
Article
Full-text available
For decades, the struggle against inflammation and related disorders has constituted an important field in medical practice, with strategies mainly aimed at inhibiting compounds produced through the arachidonic acid pathway. Thus, specific COX-2 inhibitors or "coxibs", were recently designed, that play an increasing but controversial role in reduci...
Article
Previous evidence has shown that prostaglandins play a key role in the development of sickness behavior observed during inflammatory states. In particular, prostaglandin E2 (PGE2) is produced in the brain by a variety of inflammatory signals such as endotoxins or cytokines. Its injection has been also shown to induce symptoms of sickness behavior....
Article
Full-text available
In human somatotroph adenomas, growth hormone (GH) hypersecretion can be inhibited by somatostatin analogues such as octreotide. Unfortunately, serum GH levels reach normal values in only 60% of treated patients. The decreased sensitivity to octreotide is strongly related to a lower expression of somatostatin receptor sst2. In this present study, t...
Article
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Protein kinase C (PKC) is a family of isoenzymes playing a key role in the regulation of gonadotrope cell functions. Specific PKC isoforms are activated and downregulated differentially by gonadotropin-releasing hormone (GnRH) and the phorbol ester TPA. In the present study, focusing mainly on PKC epsilon, the mechanisms underlying the proteasome-d...
Article
Anorexia-cachexia syndrome is a very common symptom observed in individuals affected by chronic inflammatory diseases. The present study was designed to address the possible involvement of the inducible microsomal prostaglandin E synthase-1 (mPGES-1) in the hypopaghia observed during these pathological states. To this end, we used a model of cancer...
Article
Full-text available
The culture of chondrocytes is one of the most powerful tools for exploring the intracellular and molecular features of chondrocyte differentiation and activation. However, chondrocytes tend to dedifferentiate into fibroblasts when they are subcultured, which is a major problem. This protocol, involving primary cultures to limit dedifferentiation,...
Article
Knee osteoarthritis (OA) results, at least in part, from overloading and inflammation leading to cartilage degradation. Prostaglandin E2 (PGE2) is one of the main catabolic factors involved in OA in which metalloproteinase (MMP) is crucial for cartilage degradation. Its synthesis is the result of cyclooxygenase (COX) and prostaglandin E synthase (P...
Article
The aim of the present study was to investigate the impact of the deletion of the microsomal prostaglandin E synthase-1 (mPGES-1) gene on lipopolysaccharide (LPS)-induced neuronal activation in central nervous structures. The mPGES-1 catalyses the conversion of COX-derived PGH(2) to PGE(2) and has been described as a regulated enzyme whose expressi...
Article
Full-text available
The anterior pituitary-specific transcription factor Pit-1 was initially identified and cloned as a transactivator of the prolactin (PRL) and GH genes and later as a regulator of the TSHb gene. It was found to be a major developmental regulator, because natural Pit-1 gene mutations cause a dwarf phenotype in mice and cause combined pituitary hormon...
Article
Full-text available
In response to infection or inflammation, individuals develop a set of symptoms referred to as sickness behavior, which includes a decrease in food intake. The characterization of the molecular mechanisms underlying this hypophagia remains critical, because chronic anorexia may represent a significant health risk. Prostaglandins (PGs) constitute an...
Article
Full-text available
Knee osteoarthritis (OA) results, at least in part, from overloading and inflammation leading to cartilage degradation. Prostaglandin E2 (PGE2) is one of the main catabolic factors involved in OA. Its synthesis is the result of cyclooxygenase (COX) and prostaglandin E synthase (PGES) activities whereas NAD+-dependent 15 hydroxy prostaglandin dehydr...
Data
Full-text available
techniques linking genes and pathways to physiology, from prokaryotes to eukaryotes. It is published quarterly in January, April, publishes results of a wide variety of studies from human and from informative model systems with Physiological Genomics on January 24, 2007 physiolgenomics.physiology.org Downloaded from
Article
Many genetically modified animal models are providing new keys for unlocking the pathophysiology of cartilage degradation. To produce a tool for cellular and molecular studies in genetically engineered murine models, we defined the optimal culture conditions for primary cultures of articular chondrocytes from newborn mice (C57Bl/6). To determine wh...
Article
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Programmed cell death (PCD) is physiologically involved in the regulation of cell division and differentiation. It encompasses caspase-dependent mitochondrial and nonmitochondrial pathways. Additional caspase-independent pathways have been characterized in mitochondrial PCDs but remain hypothetical in nonmitochondrial PCDs. Epidermal growth factor...
Article
Microsomal prostaglandin E synthase 1 (mPGES-1) is the final enzyme of the cascade that produces prostaglandin E(2) (PGE(2)), a key actor in arthritis. To study mPGES-1 synthesis in human cartilage and its regulation by interleukin-1beta (IL-1beta), we used human cartilage and an immortalized human chondrocyte cell line. Furthermore, we investigate...
Article
Full-text available
The culture of chondrocytes is one of the most powerful tool for exploring the intracellular and molecular features of chondrocyte differentiation and activation. However, chondrocytes tend to dedifferentiate to fibroblasts when they are subcultured, which is a major problem. This chapter describes several protocols for culturing chondrocytes of di...
Article
Full-text available
Extracellular ATP is a pro-inflammatory mediator involved in the release of prostaglandin from articular chondrocytes, but little is known about its effects on intracellular signaling. ATP triggered the rapid release of prostaglandin E2(PGE2) by acting on P2Y2 receptors in rabbit articular chondrocytes. We have explored the signaling events involve...
Article
Full-text available
The neurohypophysis is an original model of the CNS secretory system releasing vasopressin (AVP) and oxytocin (OXT), two neuropeptides hormones synthesized by the magnocellular neurons of the hypothalamus. Specific patterns of action potentials originating from cellular bodies of magnocellular neurons control the release of AVP and OT, but intra-ne...
Article
Pituicyte stellation in vitro represents a useful model with which to study morphological changes that occur in vivo in these cells during times of high neurohypophysial hormone output. This model has helped us establish the hypothesis of a purinergic regulation of pituicyte morphological plasticity. We first show that ATP induces stellation in 37%...
Article
Full-text available
Chondrocyte dedifferentiation has been noted in osteoarthritic cartilage, but the contribution of this phenomenon is poorly understood. Interleukin (IL)-1beta, the major pro-inflammatory cytokine found in osteoarthritic synovial fluid, induces the dedifferentiation of cultured articular chondrocytes, whereas E-series prostaglandins (PGE) are capabl...
Article
Full-text available
We have previously investigated the effects of extracellular ATP on the concentration of free cytosolic calcium ([Ca2+]i) from rat cultured neurohypophysial astrocytes (pituicytes). We demonstrated that ATP acts via a P2Y receptor to increase [Ca2+]i. In the present study, we examine the effect of ATP on K+ efflux using 86Rb+ as an isotopic tracer,...
Article
Full-text available
The effect of adenosine triphosphate (ATP) on the intracellular Ca2+ concentration ([Ca2+]i) of cultured neurohypophysial astrocytes (pituicytes) was studied by fluorescence videomicroscopy. ATP evoked a [Ca2+]i increase, which was dose dependent in the 2.5-50 microM range (EC50=4.3 microM). The ATP-evoked [Ca2+]i rise was not modified during the f...
Article
Full-text available
It is generally accepted that Ca is essentially involved in regulated secretion, but the role of this cation, as well as others such as Na, is not well understood. An illustrative example occurs in neurohypophysial secretion, where an experimentally induced increase in the cytosolic concentration of Na+ can induce continuous neuropeptide release. I...
Data
Full-text available
It is generally accepted that Ca is essentially involved in regulated secretion, but the role of this cation, as well as others such as Na, is not well understood. An illus-trative example occurs in neurohypophysial secretion, where an experimentally induced increase in the cytosolic concen-tration of Na can induce continuous neuropeptide release....
Article
Digitonin-permeabilized isolated neurohypophysial nerve terminals are known to release their secretory vesicle content under calcium challenge. On this preparation, we monitored intra-organelle Ca2+ concentration using digital fluorescence microscopy of Fura-2. The superfusion of artificial intracellular solution containing 10 to 50 microM Ca2+ ind...
Article
1. The effect of externally applied ATP on cytosolic free Ca2+ concentration ([Ca2+]i) was tested in single isolated rat neurohypophysial nerve terminals by fura-2 imaging. The release of vasopressin (AVP) and oxytocin (OT) upon ATP stimulation was also studied from a population of terminals using specific radioimmunoassays. 2. ATP evoked a sustain...
Article
The calcium content of individual secretory vesicles in rat neurohypophysial nerve endings was measured by quantitative electron probe X-ray microanalysis. Directly frozen control and potassium-depolarized isolated endings were analysed using two presumably equivalent preparative techniques: (1) freeze-substitution in presence of oxalic acid follow...
Article
Full-text available
We studied the distribution of Ca(2+)- or Mg(2+)-dependent ATPase activity in rat neurohypophysis using the lead cytochemical method of Ando et al. In electron microscopy, precipitates were found lining the outer surface of the plasma membrane surrounding nerve endings and pituicytes. These precipitates were believed to represent the activity of ec...
Article
Full-text available
We studied the distribution of Ca2' -or M$-dependent ATP ase activity in rat neurohypophysis using the lead cytochem-ical method of Ando et al. In electron microscopy, precipi-tates were found lining the outer surface of the plasma membrane surrounding nerve endings and pituicytes. These precipitates were beliwed to represent the activity of ecto-A...
Article
The total calcium content of secretory granules, Cag, was evaluated in isolated neurohypophysial nerve endings. The Cag in the resting state, as measured by X-ray microanalysis, is relatively high with an average of 7.4 +/- 0.6 mmol/kg wet weight. Following a depolarizing potassium challenge, a subpopulation of granules with even higher Cag could b...
Article
Full-text available
The review focuses on calcium accumulation by secretory organelles. The observation that secretory granules contain variable and often important quantities of calcium (1-200 mM of total calcium) can be interpreted as a maturation index. A progressive loading with calcium would be permitted by a Ca2(+)-transport mechanism on the granular membrane an...