Biomedical subjects

G Pelletier

Publications and source records attributed to G Pelletier.

At least 19 recordsLinked to original sources

PubMed2007

Expression of sulfotransferase 1E1 in human prostate as studied by in situ hybridization and immunocytochemistry.

BACKGROUND: Estrogen is recognized to play a role in the development and function of the prostate. Estrogen sulfotransferase (EST) 1E1 catalyzes the sulfoconjugation of estrogen and is thus involved in the metabolism of estrogen. We have recently shown that EST 1E1 is highly expressed in male mouse reproductive organs, including prostate. It appeared of interest to study the expression of EST 1E1 in human prostate. METHODS: EST 1E1 mRNA and protein expression was evaluated in benign prostatic hyperplasia (BPH) using in situ hybridization and immunocytochemistry, respectively. RESULTS: EST 1E1 mRNA and protein were found to be expressed in epithelial cells bordering alveola lumen (luminal cells) as well as stroma cells. CONCLUSION: The enzyme EST may play a physiological role in regulating local estrogen levels in human prostate.

Aged↗

PubMed2007

Localization and glucocorticoid regulation of 11beta-hydroxysteroid dehydrogenase type 1 mRNA in the male mouse forebrain.

The enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts the inactive 11-dehydrocorticosterone into the active glucocorticoid corticosterone. There is accumulating evidence indicating widespread expression of 11beta-HSD1 in the brain. However, there is little information about regulation of 11beta-HSD1 expression in this tissue. Using in situ hybridization involving use of 35S-labeled cRNA probe, we have studied the distribution of cells expressing 11beta-HSD1 mRNA in the male mouse forebrain as well as the effects of adrenalectomy (ADX) and acute administration of corticosterone (3 and 24 h) on 11beta-HSD1 mRNA levels. Cells expressing 11beta-HSD1 mRNA were mostly detected in the cerebral cortex, hippocampus, amygdala and medial preoptic area, with the highest expression in the cerebral cortex (retrosplenial granular area) and hippocampus (CA3 and granular layer of the gyrus dentatus). Seven days following ADX, 11beta-HSD mRNA levels were increased by 50% in the gyrus dentatus, by 100% in the CA3 area, and 105% in the cerebral cortex. Administration of corticosterone to ADX mice induced a significant decrease in mRNA, in both the hippocampus and cerebral cortex so that, at the 24 h time interval, the levels were similar to those observed in intact mice. These results clearly indicate that circulating corticosterone is downregulating the expression of 11beta-HSD1 mRNA in the two forebrain areas studied. This downregulation might contribute to maintain low intracellular corticosterone levels in central regions and then prevent the deleterious effects induced by high glucocorticoid levels.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗

PubMed2006

HESS observations of the galactic center region and their possible dark matter interpretation.

The detection of gamma rays from the source HESS J1745-290 in the Galactic Center (GC) region with the High Energy Spectroscopic System (HESS) array of Cherenkov telescopes in 2004 is presented. After subtraction of the diffuse gamma-ray emission from the GC ridge, the source is compatible with a point source with spatial extent less than 1.2;{'}(stat) (95% C.L.). The measured energy spectrum above 160 GeV is compatible with a power law with photon index of 2.25+/-0.04(stat)+/-0.10(syst) and no significant flux variation is detected. It is finally found that the bulk of the very high energy emission must have non-dark-matter origin.

Journal Article↗

PubMed2006

Fast variability of tera-electron volt gamma rays from the radio galaxy M87.

The detection of fast variations of the tera-electron volt (TeV) (10(12) eV) gamma-ray flux, on time scales of days, from the nearby radio galaxy M87 is reported. These variations are about 10 times as fast as those observed in any other wave band and imply a very compact emission region with a dimension similar to the Schwarzschild radius of the central black hole. We thus can exclude several other sites and processes of the gamma-ray production. The observations confirm that TeV gamma rays are emitted by extragalactic sources other than blazars, where jets are not relativistically beamed toward the observer.

Journal Article↗

PubMed2006

Role of androgens and glucocorticoids in the regulation of diazepam-binding inhibitor mRNA levels in male mouse hypothalamus.

In peripheral organs, gonadal and adrenal steroids regulate diazepam-binding inhibitor (DBI) mRNA expression. In order to further investigate the involvement of peripheral steroid hormones in the modulation of brain DBI mRNA expression, we studied by semiquantitative in situ hybridization the effect of adrenalectomy (ADX) and castration (CX) and short-term replacement therapy on DBI mRNA levels in the male mouse hypothalamus. Cells expressing DBI mRNA were mostly observed in the arcuate nucleus, the median eminence and the ependyma bordering the third ventricle. In the median eminence and the ependyma bordering the third ventricule, the DBI gene expression was decreased in ADX rats and a single injection of corticosterone to ADX rats induced a significant increase in DBI gene expression at 3 and 12 h time intervals without completely restoring the basal DBI mRNA expression observed in intact mice. In the arcuate nucleus, ADX and corticosterone administration did not modify DBI mRNA expression. CX down-regulated DBI gene expression in the ependyma bordering the third ventricle. The administration of dihydrotestosterone (3-24 h) completely reversed the inhibitory effect of CX. In the median eminence and arcuate nucleus, neither CX or dihydrotestosterone administration modified DBI mRNA levels. These results suggest that the effects of glucocorticoids on the hypothalamo-pituitary-adrenocortical axis and androgens on the hypothalamo-pituitary-gonadal axis are mediated by DBI.

Adrenalectomy↗

PubMed2006

Expression of aromatase and 17beta-hydroxysteroid dehydrogenase types 1, 7 and 12 in breast cancer. An immunocytochemical study.

It is known that there is a local biosynthesis of estradiol (E2) in breast carcinoma. The steroidogenic enzymes involved in E2 formation are aromatase which transforms testosterone into E2 and androstenedione into estrone (E1) and reductive 17beta-hydroxysteroid dehydrogenases (17beta-HSDs) which convert E1 into E2. Using immunocytochemistry, we have studied the expression of aromatase and the three reductive 17beta-HSDs 17beta-HSD types 1, 7 and 12 in 41 specimens of female human breast carcinoma and adjacent non-malignant tissues. These results were correlated with the estrogen receptor alpha (ERalpha) and beta (ERbeta), progesterone receptor, androgen receptor, CDC47 and c-erb B-2 expressions and with the tumor stages. Aromatase was found in 58%, 17beta-HSD type 7 in 47% and 17beta-HSD type 12 in 83% of the breast cancer specimens. The 17beta-HSD type 1 could be detected in only one tumor. A significant correlation was observed between the aromatase, 17beta-HSD type 7 and 17beta-HSD type 12 expression, as well as between each of the two enzymes 17beta-types 7 and 12 and the ERbeta expression. The expression of 17beta-HSD type 12 was significantly higher in breast carcinoma specimens than in normal tissue. There was also a significant association of CDC 47 expression with ERbeta, AR and 17beta-HSD type 12. The results indicate that aromatase, 17beta-HSD type 7 and 17beta-HSD type 12, but not 17beta-HSD type 1, are commonly expressed in human breast cancer. Moreover, the high expression of both 17beta-HSD type 12 and ERbeta in breast carcinoma cells may play a role in the development and/or progression of breast cancer.

17-Hydroxysteroid Dehydrogenases↗

PubMed2006

A low level of extragalactic background light as revealed by gamma-rays from blazars.

The diffuse extragalactic background light consists of the sum of the starlight emitted by galaxies through the history of the Universe, and it could also have an important contribution from the 'first stars', which may have formed before galaxy formation began. Direct measurements are difficult and not yet conclusive, owing to the large uncertainties caused by the bright foreground emission associated with zodiacal light. An alternative approach is to study the absorption features imprinted on the gamma-ray spectra of distant extragalactic objects by interactions of those photons with the background light photons. Here we report the discovery of gamma-ray emission from the blazars H 2356 - 309 and 1ES 1101 - 232, at redshifts z = 0.165 and z = 0.186, respectively. Their unexpectedly hard spectra provide an upper limit on the background light at optical/near-infrared wavelengths that appears to be very close to the lower limit given by the integrated light of resolved galaxies. The background flux at these wavelengths accordingly seems to be strongly dominated by the direct starlight from galaxies, thus excluding a large contribution from other sources-in particular from the first stars formed. This result also indicates that intergalactic space is more transparent to gamma-rays than previously thought.

Journal Article↗

PubMed2006

Discovery of very-high-energy gamma-rays from the Galactic Centre ridge.

The source of Galactic cosmic rays (with energies up to 10(15) eV) remains unclear, although it is widely believed that they originate in the shock waves of expanding supernova remnants. At present the best way to investigate their acceleration and propagation is by observing the gamma-rays produced when cosmic rays interact with interstellar gas. Here we report observations of an extended region of very-high-energy (> 10(11) eV) gamma-ray emission correlated spatially with a complex of giant molecular clouds in the central 200 parsecs of the Milky Way. The hardness of the gamma-ray spectrum and the conditions in those molecular clouds indicate that the cosmic rays giving rise to the gamma-rays are likely to be protons and nuclei rather than electrons. The energy associated with the cosmic rays could have come from a single supernova explosion around 10(4) years ago.

Journal Article↗

PubMed2005

In vivo action of a new octadecaneuropeptide antagonist on neuropeptide Y and corticotropin-releasing hormone mRNA levels in rat.

It has been reported that several of the effects induced by an octadecaneuropeptide (ODN), derived from an 86-amino-acid polypeptide termed diazepam-binding inhibitor, could be mediated by activation of a metabotropic receptor. In order to investigate the role and mechanism of action of ODN in the regulation of corticotropin-releasing factor (CRH) and neuropeptide Y (NPY) expression in the paraventricular nucleus and arcuate nucleus, respectively, we studied the effects of the acute intracerebroventricular administration of ODN (2 microg/rat) and the ODN antagonist to metabotropic receptor, cyclo(1-8)[Dleu5]OP (20 microg/rat), on the gene expression of the two neuropeptides in castrated male rat. ODN administration resulted in a 45% increase in CRH mRNA expression, an effect which was reversed by cyclo(1-8)[Dleu5]OP. When cyclo(1-8)[Dleu5]OP was administered alone, it induced a 19% decrease in CRH mRNA levels. ODN administration induced a 17% decrease in NPY mRNA expression while cyclo(1-8)[Dleu5]OP increased by 21% the hybridization signal. The administration of both ODN and ODN antagonist completely abolished the depressing effect of ODN on NPY mRNA. These data suggest that the effects of ODN on CRH and NPY mRNA might be mediated by interaction with metabotropic receptors. Moreover, since cyclo(1-8)[Dleu5]OP can by itself influence the expression of two peptide mRNAs, it might be suggested that ODN is exerting a tonic influence on NPY and CRH neurons.

Animals↗

PubMed2005

Discovery of very high energy gamma rays associated with an x-ray binary.

X-ray binaries are composed of a normal star in orbit around a neutron star or stellar-mass black hole. Radio and x-ray observations have led to the presumption that some x-ray binaries called microquasars behave as scaled-down active galactic nuclei. Microquasars have resolved radio emission that is thought to arise from a relativistic outflow akin to active galactic nuclei jets, in which particles can be accelerated to large energies. Very high energy gamma-rays produced by the interactions of these particles have been observed from several active galactic nuclei. Using the High Energy Stereoscopic System, we find evidence for gamma-ray emission of >100 gigaelectron volts from a candidate microquasar, LS 5039, showing that particles are also accelerated to very high energies in these systems.

Journal Article↗

PubMed2005

A new recombined double low restorer line for the Ogu-INRA cms in rapeseed (Brassica napus L.).

A major objective of breeders using the Ogu-INRA cytoplasmic male sterility (cms) system in rapeseed (Brassica napus L.) is to obtain double low restorer lines with a shorter introgression and a good agronomic value. The development of low glucosinolate content (low GC) restorer lines often occurs through the deletion of a part of the introgression. One of these lines has lost the radish Pgi-2 allele expression, without recovering that of the rapeseed Pgi-2 allele. This line shows a defect in the meiotic transmission of the restorer gene Rfo and a very poor agronomic value. We initiated a programme to force non-spontaneous recombination between this Rfo-carrying introgression and the rapeseed homologous chromosome from a low GC B. napus line. Gamma ray irradiation was used to induce chromosome breakage just prior meiosis aiming at just such a recombination. Low GC cms plants were crossed with the pollen of irradiated plants that were heterozygous for this introgression. The F(2) families were scored for their vigour, transmission rate of Rfo and female fertility. One family of plants, R2000, showed an improved behaviour for these three traits. This family presented a unique combination of molecular markers when compared to other rapeseed restorers analysed, which suggests that the recombination event allowed the recovery of B. oleracea genetic information that was originally replaced by the radish introgression in the original restorers. This resulted in a duplicated region (originating from radish and B. oleracea) on the chromosome carrying the introgression in the R2000 family.

Brassica napus↗

PubMed2005

Localization of type 5 17beta-hydroxysteroid dehydrogenase mRNA in mouse tissues as studied by in situ hybridization.

The mouse enzyme type 5 17beta-hydroxysteroid dehydrogenase (17beta-HSD) catalyzes the conversion of androstenedione to testosterone and, to a lesser degree, the conversion of estrone to estradiol. In order to determine the exact sites of action of type 5 17beta-HSD, we studied the cellular localization of the mRNA of the enzyme in mouse tissues by using in situ hybridization. Specific hybridization signal was found in the liver, ovary, adrenal cortex, and kidney. In the liver of mice of both sexes, a strong signal was observed in all hepatocytes. In the ovary, specific labeling was detected in the granulosa and theca interna cells in growing follicles and in luteal cells. In the female adrenal cortex, intense labeling was restricted to the zona reticularis, whereas no type 5 17beta-HSD mRNA expression could be found in the male adrenal cortex. In the kidney of mice of both sexes, type 5 17beta-HSD mRNA was expressed in epithelial cells in both the proximal and distal convoluted tubules. The data indicate that androgens and estrogens are formed via the action of type 5 17beta-HSD in specific cell types in the liver, ovary, adrenal cortex, and kidney.

17-Hydroxysteroid Dehydrogenases↗

PubMed2005

A new population of very high energy gamma-ray sources in the Milky Way.

Very high energy gamma-rays probe the long-standing mystery of the origin of cosmic rays. Produced in the interactions of accelerated particles in astrophysical objects, they can be used to image cosmic particle accelerators. A first sensitive survey of the inner part of the Milky Way with the High Energy Stereoscopic System (HESS) reveals a population of eight previously unknown firmly detected sources of very high energy gamma-rays. At least two have no known radio or x-ray counterpart and may be representative of a new class of "dark" nucleonic cosmic ray sources.

Journal Article↗

PubMed2005

Localization of type 7 17beta-hydroxysteroid dehydrogenase in mouse tissues. In situ hybridization studies.

The enzyme type 7 17beta-hydroxysteroid dehydrogenase (17beta-HSD) selectively catalyzes the conversion of estrone (E1) into estradiol (E2). In order to obtain detailed information about the exact sites of action of type 7 17beta-HSD, we have studied the cellular localization of type 7 17beta-HSD mRNA in mouse tissues using in situ hybridization (ISH). In parallel studies, we also measured the enzyme mRNA levels by quantitative real time (RT)-PCR. In the ovary, strong hybridization signal was restricted to corpus luteum cells. In the female mammary gland, type 7 17beta-HSD mRNA was found to be expressed in stromal cells surrounding the ducts. In the clitoral and preputial glands, specific labeling was observed in the epithelial cells of both acini and small ducts. In the adrenal gland, hybridization signal was observed in the zona fasciculata and reticularis in the cortex. In the liver, hybridization signal was found in all the hepatocytes. In the colon, type 7 17beta-HSD mRNA expression was restricted to epithelial cells of the mucosa. From the results obtained with quantitative real time RT-PCR, it appears, with a very few exceptions, that in tissues exhibiting low mRNA expression no ISH signal could be detected. The present data suggest that E2 can be formed through the action of type 7 17beta-HSD in specific cell types in the ovary and peripheral tissues, in addition to type 1 17beta-HSD, thus providing tissues with an alternative route of formation of E2.

17-Hydroxysteroid Dehydrogenases↗

PubMed2005

Androgenic down-regulation of urotensin II precursor, urotensin II-related peptide precursor and androgen receptor mRNA in the mouse spinal cord.

We had previously shown that in rat spinal cord motoneurons urotensin II (UII) precursor mRNA was down-regulated by androgens. Very recently, a gene encoding the precursor of a UII analog, termed UII-related peptide (URP), has been identified. Using in situ hybridization, we studied the localization of UII and URP precursor as well as androgen receptor (AR) mRNA in the male mouse thoracic spinal cord. We also evaluated the androgenic regulation of the two peptide precursor and AR mRNA expression in the ventral horn of the mouse thoracic spinal cord. The results revealed that URP precursor mRNA was localized in motoneurons and that the vast majority of the motoneurons expressed both peptide precursor as well as AR mRNA. Seven-day castration induced an increase in UII and URP precursor and AR mRNA levels. Short term (3-24 h) administration of dihydrotestosterone to castrated animals restored the three protein mRNA levels to the levels observed in intact animals. These results suggest that in the ventral horn of the mouse spinal cord both UII and URP precursor and AR mRNA are expressed by the same neurons and that circulating androgens are exerting a down-regulation of the three protein mRNA expression, possibly by a direct action on motoneurons.

Animals↗

PubMed2005

Is dehydroepiandrosterone a hormone?

Dehydroepiandrosterone (DHEA) is not a hormone but it is a very important prohormone secreted in large amounts by the adrenals in humans and other primates, but not in lower species. It is secreted in larger quantities than cortisol and is present in the blood at concentrations only second to cholesterol. All the enzymes required to transform DHEA into androgens and/or estrogens are expressed in a cell-specific manner in a large series of peripheral target tissues, thus permitting all androgen-sensitive and estrogen-sensitive tissues to make locally and control the intracellular levels of sex steroids according to local needs. This new field of endocrinology has been called intracrinology. In women, after menopause, all estrogens and almost all androgens are made locally in peripheral tissues from DHEA which indirectly exerts effects, among others, on bone formation, adiposity, muscle, insulin and glucose metabolism, skin, libido and well-being. In men, where the secretion of androgens by the testicles continues for life, the contribution of DHEA to androgens has been best evaluated in the prostate where about 50% of androgens are made locally from DHEA. Such knowledge has led to the development of combined androgen blockade (CAB), a treatment which adds a pure anti-androgen to medical (GnRH agonist) or surgical castration in order to block the access of the androgens made locally to the androgen receptor. In fact, CAB has been the first treatment demonstrated to prolong life in advanced prostate cancer while recent data indicate that it can permit long-term control and probably cure in at least 90% of cases of localized prostate cancer. The new field of intracrinology or local formation of sex steroids from DHEA in target tissues has permitted major advances in the treatment of the two most frequent cancers, namely breast and prostate cancer, while its potential use as a physiological HRT could well provide a physiological balance of androgens and estrogens, thus offering exciting possibilities for women's health at menopause.

Adult↗

PubMed2004

High-energy particle acceleration in the shell of a supernova remnant.

A significant fraction of the energy density of the interstellar medium is in the form of high-energy charged particles (cosmic rays). The origin of these particles remains uncertain. Although it is generally accepted that the only sources capable of supplying the energy required to accelerate the bulk of Galactic cosmic rays are supernova explosions, and even though the mechanism of particle acceleration in expanding supernova remnant (SNR) shocks is thought to be well understood theoretically, unequivocal evidence for the production of high-energy particles in supernova shells has proven remarkably hard to find. Here we report on observations of the SNR RX J1713.7 - 3946 (G347.3 - 0.5), which was discovered by ROSAT in the X-ray spectrum and later claimed as a source of high-energy gamma-rays of TeV energies (1 TeV = 10(12) eV). We present a TeV gamma-ray image of the SNR: the spatially resolved remnant has a shell morphology similar to that seen in X-rays, which demonstrates that very-high-energy particles are accelerated there. The energy spectrum indicates efficient acceleration of charged particles to energies beyond 100 TeV, consistent with current ideas of particle acceleration in young SNR shocks.

Journal Article↗

PubMed2004

Localization of 20alpha-hydroxysteroid dehydrogenase mRNA in mouse brain by in situ hybridization.

The enzyme 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD) catalyzes the conversion of progesterone into its inactive form, 20alpha-hydroxyprogesterone. We studied the expression of 20alpha-HSD mRNA in mouse brain by in situ hybridization. 20alpha-HSD mRNA was exclusively found in neurons in cortex and hippocampus. In the cortex, the labelled cells were concentrated in the external granular layer, the external pyramidal layer and the inner granular layer. In the hippocampus, the labelling was mostly located over pyramidal cells of the CA1 layer. These results suggest that progesterone can be inactivated by 20alpha-HSD in some specific brain areas.

20-alpha-Hydroxysteroid Dehydrogenase↗