Physiopathological role of the enzymatic complex 5α-reductase and 3α/β-hydroxysteroid oxidoreductase in the generation of progesterone and testosterone neuroactive metabolites

The enzymatic complex 5\u3b1-reductase (5\u3b1-R) and 3\u3b1/3\u3b2-hydroxysteroid oxidoreductase (HSOR) is expressed in the nervous system, where it transforms progesterone (PROG) and testosterone (T) into neuroactive metabolites. These metabolites regulate myelination, brain maturation, neurotransmission, reproductive behavior and the stress response. The expression of 5\u3b1-R and 3\u3b1-HSOR and the levels of PROG and T reduced metabolites show regional and sex differences in the nervous system and are affected by changing physiological conditions as well as by neurodegenerative and psychiatric disorders. A decrease in their nervous tissue levels may negatively impact the course and outcome of some pathological events. However, in other pathological conditions their increased levels may have a negative impact. Thus, the use of synthetic analogues of these steroids or 5\u3b1-R modulation have been proposed as therapeutic approaches for several nervous system pathologies. However, further research is needed to fully understand the consequences of these manipulations, in particular with 5\u3b1-R inhibitors

Sex differences in steroid levels and steroidogenesis in the nervous system : Physiopathological role

The nervous system, in addition to be a target for steroid hormones, is the source of a variety of neuroactive steroids, which are synthesized and metabolized by neurons and glial cells. Recent evidence indicates that the expression of neurosteroidogenic proteins and enzymes and the levels of neuroactive steroids are different in the nervous system of males and females. We here summarized the state of the art of neuroactive steroids, particularly taking in consideration sex differences occurring in the synthesis and levels of these molecules. In addition, we discuss the consequences of sex differences in neurosteroidogenesis for the function of the nervous system under healthy and pathological conditions and the implications of neuroactive steroids and neurosteroidogenesis for the development of sex-specific therapeutic interventions

Evaluation of neuroactive steroid levels by liquid chromatography-tandem mass spectrometry in central and peripheral nervous system : effect of diabetes

The nervous system is a target for physiological and protective effects of neuroactive steroids. Consequently, the assessment of their levels in nervous structures under physiological and pathological conditions is a top priority. To this aim, identification and quantification of pregnenolone (PREG), progesterone (PROG), dihydroprogesterone (DHP), tetrahydroprogesterone (THP), testosterone (T), dihydrotestosterone (DHT), 5aandrostan- 3a, 17b-diol (3a-diol), 17a- and 17b-estradiol (17a-E and 17b-E) by liquid chromatography and tandem mass spectrometry (LC\u2013MS/ MS) has been set up. After validation, this method was applied to determine the levels of neuroactive steroids in central (i.e., cerebral cortex, cerebellum and spinal cord) and peripheral (i.e., brachial nerve) nervous system of control and diabetic rats. In controls only the brachial nerve had detectable levels of all these neuroactive steroids. In contrast, 17a-E in cerebellum, 17a-E, 17b-E, DHP and THP in cerebral cortex, and 17a-E, 17b-E and DHP in spinal cord were under the detection limit. Diabetes, induced by injection with streptozotocin, strongly affected the levels of some neuroactive steroids. In particular, the levels of PREG, PROG and T in cerebellum, of PROG, T and 3a-diol in cerebral cortex, of PROG, DHTand 3a-diol in spinal cord and of PREG, DHP, THP, T, DHTand 3a-diol in brachial nerve were significantly decreased. In conclusion, the data here reported demonstrate that the LC\u2013MS/MS method allows the assessment of neuroactive steroids in the nervous system with high sensitivity and specificity and that diabetes strongly affects their levels, providing a further basis for new therapeutic tools based on neuroactive steroids aimed at counteracting diabetic neuropathy

Estudio teórico y experimental del sistema 9 Be + 51 V y sistemas similares

En este trabajo de tesis se presenta el estudio sistemático de los sistemas 7Li + 51V, 9Be + 51V y 8B + 58Ni. Para los sistemas ( 7Li, 9 Be) + 51V se midieron las secciones eficaces de fusión a energías cercanas a la barrera Coulombiana (EB,lab=11.75 y 16.16 MeV, respectivamente) empleando la técnica de rayos γ. El experimento para medir la fusión se llevó a cabo en el Laboratorio del Acelerador Tan- dem, del Instituto Nacional de Investigaciones Nucleares (ININ), siendo éstas las primeras mediciones realizadas para estos proyectiles a las energías consideradas. De forma simultánea, se hizo el análisis de los posibles núcleos residuales usando los códigos computacionales de fusión-evaporación PACE2, LILITA y CASCADE. Los resultados obtenidos fueron comparados con los datos experimentales me- didos. De forma preliminar, para el sistema 7Li + 51V, se hicieron cálculos usando la teoría de canales acoplados de reacción para estimar la contribución de la sección eficaz de transferencia de un protón a la producción del núcleo residual 52Cr. Para el sistema 8B + 58Ni, se hizo un análisis teórico de canales acoplados con el continuo discretizado y canales acoplados de reacción para estudiar los procesos de rompimiento y de transfe- rencia de un protón, 58Ni(8B,7Be)59Cu, a energías alrededor de la barrera Coulombiana (EB,lab=22.95 MeV). Para calcular las secciones eficaces correspondientes se usó un potencial de Modelo Óptico se- mimicroscópico, el cual combina un potencial real de doble convolución, un potencial de polarización y un potencial imaginario tipo Woods-Saxon. A partir de la comparación de nuestros cálculos con datos experimentales se determinaron los factores espectroscópicos Sexpt y astrofísicos S17(0) del protón en la interacción 8B → 7Be+p

Estradiol synthesis within the human brain

Estradiol biosynthesis is catalyzed by the enzyme aromatase, the product of the CYP19A1 gene. Aromatase is expressed in the brain, where it is involved not only in the control of neuroendocrine events and reproduction, but also in the regulation of neural development, synaptic plasticity and cell survival. In this review we summarize the existing data related with the detection of aromatase in human brain, with particular emphasis in the so-called “non-primary reproductive” areas. Besides hypothalamus, amygdala and preoptic/septal areas, aromatase is expressed in certain regions of basal forebrain, cerebral cortex, hippocampus, thalamus, cerebellum and brainstem of the human brain. Aromatase in human brain is produced by neurons, but there is also an astrocyte subpopulation that constitutively expresses the enzyme. The use of different methodological approaches, including the in vivo analysis by positron emission tomography of human subjects, has permitted to draw a general map of human brain aromatase, but the detailed distribution map is still far to be completed. On the other hand, despite the fact that there is only one aromatase protein, there are multiple mRNA transcripts that differ in the 5'-untranslated region, where regulatory elements reside. To date, some of the aromatase transcripts characteristic of cerebral cortex, as well as of human cell lines of neural origin, have been identified. This characteristic may confer tissue or even region-specific regulation of the expression and therefore it is conceivable to develop selective aromatase modulators to regulate the expression of the enzyme in the human brai

Observation of a new chi_b state in radiative transitions to Upsilon(1S) and Upsilon(2S) at ATLAS

The chi_b(nP) quarkonium states are produced in proton-proton collisions at the Large Hadron Collider (LHC) at sqrt(s) = 7 TeV and recorded by the ATLAS detector. Using a data sample corresponding to an integrated luminosity of 4.4 fb^-1, these states are reconstructed through their radiative decays to Upsilon(1S,2S) with Upsilon->mu+mu-. In addition to the mass peaks corresponding to the decay modes chi_b(1P,2P)->Upsilon(1S)gamma, a new structure centered at a mass of 10.530+/-0.005 (stat.)+/-0.009 (syst.) GeV is also observed, in both the Upsilon(1S)gamma and Upsilon(2S)gamma decay modes. This is interpreted as the chi_b(3P) system.Comment: 5 pages plus author list (18 pages total), 2 figures, 1 table, corrected author list, matches final version in Physical Review Letter

Search for displaced vertices arising from decays of new heavy particles in 7 TeV pp collisions at ATLAS

We present the results of a search for new, heavy particles that decay at a significant distance from their production point into a final state containing charged hadrons in association with a high-momentum muon. The search is conducted in a pp-collision data sample with a center-of-mass energy of 7 TeV and an integrated luminosity of 33 pb^-1 collected in 2010 by the ATLAS detector operating at the Large Hadron Collider. Production of such particles is expected in various scenarios of physics beyond the standard model. We observe no signal and place limits on the production cross-section of supersymmetric particles in an R-parity-violating scenario as a function of the neutralino lifetime. Limits are presented for different squark and neutralino masses, enabling extension of the limits to a variety of other models.Comment: 8 pages plus author list (20 pages total), 8 figures, 1 table, final version to appear in Physics Letters

Reducing heterotic M-theory to five dimensional supergravity on a manifold with boundary

This paper constructs the reduction of heterotic $M$-theory in eleven dimensions to a supergravity model on a manifold with boundary in five dimensions using a Calabi-Yau three-fold. New results are presented for the boundary terms in the action and for the boundary conditions on the bulk fields. Some general features of dualisation on a manifold with boundary are used to explain the origin of some topological terms in the action. The effect of gaugino condensation on the fermion boundary conditions leads to a `twist' in the chirality of the gravitino which can provide an uplifting mechanism in the vacuum energy to cancel the cosmological constant after moduli stabilisation.Comment: 16 pages, RevTe

Measurement of the inclusive isolated prompt photon cross-section in pp collisions at sqrt(s)= 7 TeV using 35 pb-1 of ATLAS data

A measurement of the differential cross-section for the inclusive production of isolated prompt photons in pp collisions at a center-of-mass energy sqrt(s) = 7 TeV is presented. The measurement covers the pseudorapidity ranges |eta|<1.37 and 1.52<=|eta|<2.37 in the transverse energy range 45<=E_T<400GeV. The results are based on an integrated luminosity of 35 pb-1, collected with the ATLAS detector at the LHC. The yields of the signal photons are measured using a data-driven technique, based on the observed distribution of the hadronic energy in a narrow cone around the photon candidate and the photon selection criteria. The results are compared with next-to-leading order perturbative QCD calculations and found to be in good agreement over four orders of magnitude in cross-section.Comment: 7 pages plus author list (18 pages total), 2 figures, 4 tables, final version published in Physics Letters