Collège de France

About: Collège de France is a education organization based out in Paris, France. It is known for research contribution in the topics: Population & Receptor. The organization has 6541 authors who have published 11983 publications receiving 648742 citations. The organization is also known as: College de France.

Selective activation of mesocortical DA system by stress.

Abstract: IT is now well established that an important system of dopaminergic (DA) neurones innervates various parts of the cerebral cortex in the rat and other species1–3. In contrast to noradrenergic (NA) terminals which are widely distributed in this structure, the DA terminals are mainly confined to deep layers, particularly in the frontal, the cingular and the entorhinal areas4,5. The results of lesion studies demonstrated that the terminal endings in the frontal cortex originate from the A10 group of DA cell bodies localised in the mesencephalon6–8. This group also contains the cell bodies of the classical mesolimbic DA system projecting to the tuberculum olfactorium, the nucleus accumbens, the nucleus of the stria terminalis, and the amydgala9. The DA terminals found in the cingulate and entorhinal areas of cortex may originate mainly from the A9 group of DA neurones6–8. This group gives rise to the well known nigrostriatal DA system which is implicated in extrapyramidal processes. Its degeneration is in part responsible for some of the symptoms seen in Parkinsonian patients. Little is yet known about the functions of the mesocortical and mesolimbic DA pathways. Electrocoagulation or 6-hydroxydopamine (6-OHDA)-induced lesions of the ventral tegmental area, containing the A10 group, produce a syndrome characterised by “locomotor hyperactivity, serious impairment in tests requiring inhibition of a previously learned response, facilitation of approach learning and of active avoidance and hypoemotivity”10,11. Various workers have suggested that the antipsychotic effects of neuroleptics are in part related to the blockade of postsynaptic DA receptors localised in areas innervated by the mesolimbic and mesocortical DA systems12,13. It seems important to establish whether neurones of these two DA systems correspond to an homogeneous population of cells with similar functional characteristics. We have therefore explored this problem in the rat by examining the reactivity of the mesocortical and mesolimbic DA pathways as well as that of nigrostriatal DA system to stress induced by electric foot shocks. Our results suggest that the mesocortical DA system is selectively activated by this stress.

Effect of single and compound knockouts of estrogen receptors alpha (ERalpha) and beta (ERbeta) on mouse reproductive phenotypes.

Abstract: The functions of estrogen receptors (ERs) in mouse ovary and genital tracts were investigated by generating null mutants for ERalpha (ERalphaKO), ERbeta (ERbetaKO) and both ERs (ERalphabetaKO). All ERalphaKO females are sterile, whereas ERbetaKO females are either infertile or exhibit variable degrees of subfertility. Mast cells present in adult ERalphaKO and ERalphabetaKO ovaries could participate in the generation of hemorrhagic cysts. Folliculogenesis proceeds normally up to the large antral stage in both ERalphaKO and ERbetaKO adults, whereas large antral follicles of ERalpha+/-ERbetaKO and ERalphabetaKO adults are markedly deficient in granulosa cells. Similarly, prematurely developed follicles found in prepubertal ERalphaKO ovaries appear normal, but their ERalphabetaKO counterparts display only few granulosa cell layers. Upon superovulation treatment, all prepubertal ERalphaKO females form numerous preovulatory follicles of which the vast majority do not ovulate. The same treatment fails to elicit the formation of preovulatory follicles in half of the ERbetaKO mice and in all ERalpha+/-/ERbetaKO mice. These and other results reveal a functional redundancy between ERalpha and ERbeta for ovarian folliculogenesis, and strongly suggest that (1) ERbeta plays an important role in mediating the stimulatory effects of estrogens on granulosa cell proliferation, (2) ERalpha is not required for follicle growth under wild type conditions, while it is indispensable for ovulation, and (3) ERalpha is also necessary for interstitial glandular cell development. Our data also indicate that ERbeta exerts some function in ERalphaKO uterus and vagina. ERalphabetaKO granulosa cells localized within degenerating follicles transform into cells displaying junctions that are unique to testicular Sertoli cells. From the distribution pattern of anti-Mullerian hormone (AMH) in ERalphabetaKO ovaries, it is unlikely that an elevated AMH level is the cause of Sertoli cell differentiation. Our results also show that cell proliferation in the prostate and urinary bladder of old ERbetaKO and ERalphabetaKO males is apparently normal.

A canonical structure for the ligand-binding domain of nuclear receptors.

Abstract: The ability of nuclear receptors (NRs) to activate transcription of target genes requires the binding of cognate ligands to their ligand-binding domains (LBDs). Information provided by the three-dimensional structures of the unliganded RXR alpha and the liganded RAR gamma LBDs has been incorporated into a general alignment of the LBDs of all NRs. A twenty amino-acid region constitutes a NR-specific signature and contains most of the conserved residues that stabilize the core of the canonical fold of NR LBDs. A common ligand-binding pocket, involving predominantly hydrophobic residues, is inferred by homology modelling of the human RXR alpha and glucocorticoid receptor ligand-binding sites according to the RAR gamma holo-LBD structure. Mutant studies support these models, as well as a general mechanism for ligand-induced activation deduced from the comparison of the transcriptionally active RAR gamma holo- and inactive RXR alpha apo-LBD structures.