Effects of Thyroid Hormone on Regulation of Lipolysis and Adenosine 3′,5′-Monophosphate Metabolism in 3T3-L1 Adipocytes

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Abstract
Cultured 3T3-L1 adipocytes have been used to assess direct effects of T3 [triiodothyronine] on .beta.-adrenergic-mediated regulation of lipolysis and adenylate cyclase and phosphodiesterase activities. Differentiated 3T3-L1 adipocytes were maintained under 4 conditions: in the presence of medium containing serum from a hypothyroid calf (hypothyroid medium), hypothyroid medium supplemented with T3 (T3-supplemented hypothyroid medium), medium with serum from a normal calf (control medium), and control medium supplemented with excess T3 (hyperthryoid medium). Compared to the 2 control groups, (i.e., cells maintained in control medium or T3-supplemented hypothyroid medium, cells maintained in hypothyroid medium) exhibited lower basal rates of lipolysis and lower sensitivity to isoproterenol. Hyperthyroid cells exhibited higher basal rates of lipolysis and higher sensitivity to isoproterenol. In the presence of maximally effective concentrations of isoproterenol, rates of lipolysis were similar in the 4 groups. Similarly, basal cAMP content and cAMP accumulation in the presence of isoproterenol were reduced in hypothyroid and increased in hyperthyroid adipocytes compared to those adipocytes maintained in control or T3-supplemented hypothyroid medium. Basal adenylate cyclase activity was similar in the 4 groups. Sensitivity to isoproterenol and maximal isoproterenol-stimulated cyclase activity were diminished in membrane preparations from hypothyroid adipocytes and increased in preparations from hyperthyroid adipocytes. Cyclase activity in the presence of NaF, however, was similar in preparations from cells maintained in hypothyroid, T3-supplemented hypothyroid, or control medium. NaF-stimulated activity was increased in preparations from hyperthyroid adipocytes. Thyroid status did not affect .beta.-receptor number or affinity for iodohydroxybenzylpindolol. Compared to control cells or cells maintained in T3-supplemented hypothyroid medium, both soluble and particulate cAMP phosphodiesterase activities were incresed in hypothyroid cells and decreased in hyperthyroid cells. In 3T3-L1 adipocytes, some of the effects of the effects of thyroid hormone on cAMP content and lipolysis can be explained by alterations in both production and degradation of cAMP.

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