Thyroid Effects on Adenosine 3′,5′-Monophosphate Levels and Adenylate Cyclase in Cultured Neuroblastoma Cells*

Abstract

Using neuroblastoma cells as a model of developing neurons, we have tested the hypothesis that thyroid hormones alter cAMP metabolism. Neuroblastoma cells were grown in serum-free defined medium for 48 h with or without thyroid hormones. Treatment with 20-200 nM 3,5,3'-triiodo-L-thyronine (T3) increased the accumulation of cAMP by intact cells without altering growth, gross morphology, or DNA or protein content. The increase in cAMP accumulation could be detected 5 h after the addition of T3 and was abolished by the addition of cycloheximide. The maximum stimulation produced by prostaglandin E1 was increased in T3 cells without a significant alteration of the half-maximal concentration. T4 and D-T3 in concentrations up to 20 microM did not increase cAMP accumulation. Adenylate cyclase activity in response to forskolin, guanine nucleotides, and stimulatory hormones was increased in purified membranes from cells grown in T3, suggesting that increased adenylate cyclase is probably the major mechanism of the observed response to thyroid hormone.

Synergistic Differentiation by Chronic Exposure to Cyclic AMP and Nerve Growth Factor Renders Rat Phaeochromocytoma PC12 Cells Totally Dependent upon Trophic Support for Survival

“…and perhaps to neuronal cells as well. Supporting this view, cAMP analogues have been reported to potentiate the differentiation of pituitary cytotropic factor-and basic fibroblast growth factor-sensitive dopaminergic neurons in the hypothalamus and the mesencephalon respectively (Porter et al, 1991;Hartikka et al, 1992); NGF-responsive sympathetic neurons from the superior cervical ganglion (Rydel and Greene, 1988); and NGF-responsive magnocellular cholinergic neurons from the septa1 area possibly through thyroid hormone stimulation (Hefti et al, 1986;Hayashi and Patel, 1987;Walz and Howlett, 1987). The growth hormone/cAMP potentiation may therefore be a widespread mechanism of neuronal cell differentiation and survival.…”

Rise of Intrasynaptosomal Ca2+ Level and Activation of Nitric Oxide Synthase in Adult Rat Cerebral Cortex Pretreated with 3-5-3′-L-Triiodothyronine

“…Specific membrane-binding sites of 3,5,3 Ј -L -triiodothyronine (T 3 ) have been demonstrated in the synaptosomal fraction of adult rat brain (Mashio et al 1982(Mashio et al , 1983Sarkar and Ray 1998). Direct membrane effects of T 3 lead to the inhibition of synaptosomal Na ϩ -K ϩ -ATPase activity (Sarkar and Ray 1998), involvement of a GTP-binding protein (Giguere et al 1996) and the increased activity of adenylate cyclase (Waltz and Howlett 1987), which seem to be the possible mechanism of nongenomic response of TH in neurones. The rapid influx of Ca 2 ϩ in the depolarizationinduced adult rat cerebrocortical synaptosomes is also supportive to the extranuclear action of TH (Mason et al 1990).…”

“Quo Vadis?” Deciphering the Code of Nongenomic Action of Thyroid Hormones in Mature Mammalian Brain

“…Based on these results it was also hypothesized that L-T3-effect would alter adenylate cyclase activity. In cultured neuroblastoma plasma membrane increased adenylate cyclase activity was noticed followed by L-T3-treatment [65]. In fact, later, increased adenylate cyclase activity was noticed in brain hypothyroid condition which increases brain L-T3 levels.…”