University of Turku, Department of Physiology, Biomedicine Institute, Kiinamyllynkatu 10, FI-20520 TURKU, Finland
Henriette Undeutsch, MSc; Christoffer Löf, PhD
The goal of the projects:
The group aims to provide new information about the role of different G protein, microRNA, G protein-coupled receptor and other novel signaling pathways in thyroid function using already generated, and by generating new, thyroid specific knockout models. On the basis of these in vivo and in vitro studies it will be possible to gain more insight into thyroid function. Eventually, the elucidation of the molecular processes underlying the regulation of the thyroid gland will have considerable impact on the understanding of the pathogenesis of various thyroid disorders and may lead to new prophylactic or therapeutic approaches for thyroid gland diseases or other related endocrinological diseases.
Besides the basic research projects, the group investigates the epidemiology and genetics of congenital hypothyroidism (CH), which is one of the most common preventable causes of mental retardation affecting every 1:3000 newborn worldwide. The incidence of CH has been reported to be increasing, but the etiology is largely unknown. The genetics of CH has not been studied in Finland so far. We aim to find novel causes for CH using both well-documented register information and up to date genetic methods. We believe that our work can provide important information with respect to the etiology and mechanism of congenital hypothyroidism.
NOVEL GENE MUTATIONS IN THYROID DISEASES
TSHR AND G-PROTEIN SIGNALING IN THYROID
ROLE OF MICRORNAs IN THYROID PHYSIOLOGY
Undeutsch H, Löf C, Offermanns S, Kero J. (2014) A mouse model with tamoxifen-inducible thyrocyte-specific cre recombinase activity. Genesis. doi: 10.1002/dvg.22740. [Epub ahead of print]
Kero J, Ahmed K, Wettschureck N, Tunaru S, Wintermantel T, Greiner E, Schütz G, Offermanns S. (2007) Thyrocyte-specific Gq/G11 deficiency impairs thyroid function and prevents goiter development. J Clin Invest. 117:2399-407.
Kero, J., Poutanen, M., Zhang, F.P., Rahman, N., McNicol, A.M., Nilson, J.H., Keri, R.A. & Huhtaniemi, I.T. Elevated luteinizing hormone induces expression of its receptor and promotes steroidogenesis in the adrenal cortex. J Clin Invest 105, 633-41 (2000).
Tunaru, S., Kero, J., Schaub, A., Wufka, C., Blaukat, A., Pfeffer, K. & Offermanns, S. PUMA-G and HM74 are receptors for nicotinic acid and mediate its anti-lipolytic effect. Nat Med 9, 352-5 (2003).
Taggart, A.K., Kero, J. et al. (D)-beta-Hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G. J Biol Chem 280, 26649-52 (2005).
Benyo, Z., Gille, A., Kero, J., Csiky, M., Suchankova, M.C., Nusing, R.M., Moers, A., Pfeffer, K. & Offermanns, S. GPR109A (PUMA-G/HM74A) mediates nicotinic acid-induced flushing. J Clin Invest 115, 3634-40 (2005).
Kero, J.T., Savontaus, E., Mikola, M., Pesonen, U., Koulu, M., Keri, R.A., Nilson, J.H., Poutanen, M. & Huhtaniemi, I.T. Obesity in transgenic female mice with constitutively elevated luteinizing hormone secretion. Am J Physiol Endocrinol Metab 285, E812-8 (2003).
Tom Krietsch, Maria Sofia Fernandes, Jukka Kero, Maria Heyens, Eric W.-F. Lam, Ilpo Huhtaniemi, Jan J. Brosens, and Birgit Gellersen Human Homologs of the Putative G Protein-Coupled Membrane Progestin Receptors (mPRa, b, c) Localize to the Endoplasmic Reticulum and are Not Activated by Progesterone. Mol Endocrinol. 20, 3146-64. (2006)
|Models for thyroid diseases|