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Hans H. Zingg, MD, PhD Professor and Director Laboratory of Molecular Endocrinology, RVH, Room H7.63 Tel: (514) 843-1553 Fax: (514) 982-0893 hans [dot] zingg [at] mcgill [dot] ca (Email) |
Research:
- Molecular mechanism of oxytocin receptor signaling.
- Genome-wide analysis of uterine gene expression patterns.
- Genome-wide analysis of estrogen response genes in uterus, mammary gland and bone.
Work in our laboratory focuses on the molecular mechanisms mediating oxytocin action. The oxytocin receptor is a member of the large family of G protein-coupled receptors. We are currently investigating the functional importance of receptor dimerization and oligomerization, the coupling of the receptor to tyrosine abd serine/threonine kinases, and the mechanisms of receptor phosphorylation and internalization. The nonapeptide oxytocin is involved in the mediation of a large list of biologically important functions. These include uterine contraction at parturition, milk ejection during lactation, induction of specific mating and maternal behaviours, pituitary PRL release, stimulation of thymic lymphocyte development and salt excretion by the kidney.
In a parallel project, we are using DNA microarray technology to assess on a genome-wide basis the patterns of uterine gene expression during gestation and at parturition. The overall aim of this study is to further clarify the mechanisms leading to parturition and to identify novel potential drug targets for the prevention of preterm labor.
Lastly, we have also begun to characterize, using again DNA microarrays, the differential response of the entire population of early, intermediate and late estrogen response genes in 3 different estrogen target tissues, mammary gland, uterus and bone. The results from these studies have relevance for the design of hormone replacement therapies.
Selected Publications:
Lefebvre, D., Giaid, A., Lariviere, R. and Zingg, H.H. (1992) Oxytocin gene expression in rat uterus. Science 256: 1553-1555.
Rozen, F., Russo, C., Banville, D. and Zingg, H.H. (1995) Structure, characterization and expression of the rat oxytocin receptor gene. Proc. Natl. Acad. Sci. USA 92: 200-204.
Gutkowska, J., Jankowski, M., Lambert, C., Mukaddam-Daher, S., Zingg, H.H. and McCann, S.M. (1997) Oxytocin releases atrial natriuretic peptide by combining with oxytocin receptors in the heart. Proc. Natl. Acad. Sci. USA 94: 11704-11709.
Grazzini, E., Guillon, G., Mouillac, B.and Zingg, H.H. (1998) Progesterone inhibits oxytocin receptor functions via a non-genomic mechanism. Nature 392: 509-512.
Breton, C., Di Scala-Guenot, D. and Zingg, H.H. (2001) Oxytocin receptor gene expression in rat mammary gland: Structural characterization and regulation. J. Mol. Endocrinol. 27: 175-189.
Breton, C., Chellil, H., Kabaj-Benmansour, M., Camazzi, E., Seyer, R., Phalipou, S., Morin, D., Durroux, T., Barberis, C., Zingg, H.H. and Mouillac, B. (2001) Direct identification of human oxytocin receptor-binding domains using a photoactivatable cyclic peptide antagonist: Comparison with the human V1a vasopressin receptor. J. Biol. Chem. 276: 26931-26941.