title: Different mitogen-mediated Beta-adrenergic receptor modulation in murine T lymphocytes depending on the thyroid status.
abstract: OBJECTIVE
  The aim of this work was to analyze beta-adrenergic receptor (betaAR) regulation of T-lymphocyte proliferation in mice according to different thyroid hormone statuses.
  
  
  METHODS
  T cells from eu-, hypo- (by propylthiouracil treatment) and hyperthyroid (by thyroxine, T4 administration) mice were purified and specific radioligand binding assays were performed. The effects of the beta-agonist isoproterenol (ISO) on intracellular levels of cyclic AMP (cAMP) were determined. Mitogen-induced T-cell proliferation was measured by [(3)H]-thymidine incorporation. Finally, protein kinase C (PKC) activity in cytosol and membrane fractions were determined using radiolabelled enzymatic substrates.
  
  
  RESULTS
  Adecrease or a non-significant increase in betaAR number was found on T lymphocytes from hypo- and hyperthyroid mice compared to euthyroid controls. ISO stimulation of cAMP levels was lower in hypothyroid and higher in hyperthyroid T lymphocytes compared to controls. T-selective mitogen-induced proliferation was increased in T4-treated animals, but decreased in hypothyroid mice. During the peak of proliferation, downregulation of betaAR was observed in all animals. However, a higher or a lower decrease was observed in hyper- and hypothyroid T cells, respectively. In parallel, a higher translocation of PKC activity was observed in hyperthyroid cells, and a lower one was found in hypothyroid lymphocytes with respect to controls.
  
  
  CONCLUSIONS
  These results indicate that intracellular signals triggered by mitogen activation, namely PKC, would be related to differential betaAR downregulation in T lymphocytes depending on the thyroid hormone status, contributing to the distinct proliferative responses found in hypo- or hyperthyroidism compared to the euthyroid state.
authors.affiliation: Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Alicia Juana
authors.initials: AJ
authors.lastname: Klecha
authors.forename: María Laura
authors.initials: ML
authors.lastname: Barreiro Arcos
authors.forename: Ana María
authors.initials: AM
authors.lastname: Genaro
authors.forename: Gabriela
authors.initials: G
authors.lastname: Gorelik
authors.forename: Dafne Magalí
authors.initials: DM
authors.lastname: Silberman
authors.forename: Ricardo
authors.initials: R
authors.lastname: Caro
authors.forename: Graciela Alicia
authors.initials: GA
authors.lastname: Cremaschi
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D000242:Cyclic AMP / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D005260:Female; D006980:Hyperthyroidism / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism; D007037:Hypothyroidism / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008934:Mitogens / Q000494:pharmacology*; D015213:Neuroimmunomodulation / Q000235:genetics / Q000276:immunology*; D011441:Propylthiouracil / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects / Q000276:immunology; D011940:Receptor Aggregation / Q000187:drug effects / Q000276:immunology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D013936:Thymidine / Q000378:metabolism; D013961:Thyroid Gland / Q000276:immunology / Q000378:metabolism*; D013974:Thyroxine / Q000494:pharmacology
chemical_list: D000318:Adrenergic beta-Agonists; D008934:Mitogens; D011943:Receptors, Adrenergic, beta; D011441:Propylthiouracil; D000242:Cyclic AMP; D011493:Protein Kinase C; D007545:Isoproterenol; D013974:Thyroxine; D013936:Thymidine