Triiodothyronine causes rapid reversal of alpha 1/cyclic adenosine monophosphate synergism on brown adipocyte respiration and type II deiodinase activity
| Autor: | Norma Moolten, P. Reed Larsen, Michael Noronha, Atso Raasmaja |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
medicine.medical_specialty
endocrine system diseases Endocrinology Diabetes and Metabolism Deiodinase Iodide Peroxidase chemistry.chemical_compound Endocrinology Oxygen Consumption Adipose Tissue Brown Hypothyroidism Adipocyte Internal medicine Brown adipose tissue medicine Cyclic AMP Animals Cyclic adenosine monophosphate Forskolin Triiodothyronine biology Drug Synergism Cirazoline medicine.anatomical_structure chemistry biology.protein Thermogenesis Adrenergic alpha-Agonists |
| Zdroj: | Metabolism: clinical and experimental. 40(12) |
| ISSN: | 0026-0495 |
| Popis: | Previous studies have shown that thyroid status affects the response of brown adipose tissue (BAT) to the sympathetic nervous system. For example, hypothyroidism is associated with the development of a marked synergism between alpha 1- and beta-adrenergic pathways to stimulate type II iodothyronine 5'-deiodinase activity. Hypothyroidism also attenuates the respiratory response (thermogenesis) of isolated brown adipocytes to norepinephrine. To explore the interactions of the sympathetic nervous system and thyroid status in these cells, we compared the thermogenic and 5'-deiodinase responses to adrenergic agonists in isolated brown adipocytes from hypothyroid rats during treatment with 3,5,3'-triiodothyronine (T3). The fivefold synergism of alpha 1- and beta-adrenergic catecholamines to increase the deiodinase activity was progressively reduced, reaching a control euthyroid value of unity after 5 days of T3 treatment. Hypothyroidism reduced both the O2max (twofold to threefold) and increased the concentration of agonist required for 50% stimulation (10-fold) for both norepinephrine and forskolin. In hypothyroid cells, there was a twofold synergism between the alpha 1-agonist cirazoline and forskolin to increase respiration, which was blocked by prazosin and reproduced by the calcium ionophore, A23187. This synergistic effect of the alpha 1-agonist was lost within 2 days of T3 administration. These studies identify a second Ca(2+)-dependent intra-adrenergic synergism, which functions to ameliorate the reduced cyclic adenosine monophosphate (cAMP) responsiveness of the hypothyroid brown adipocyte. |
| Databáze: | OpenAIRE |
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