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- Author: C. Massart x
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ABSTRACT
It is well known that some volatile anaesthetic drugs, such as halothane and isoflurane, alter the functions of the human thyroid gland, but the action of other anaesthetic drugs, such as thiopental, midazolam and ketamine, on thyroid function is still unknown. We have investigated the effects of these three drugs on the functional properties of human thyrocytes cultured in monolayers or follicles and stimulated by TSH. Thiopental, midazolam and ketamine induced total suppression or a partial reduction, depending on the dose administered, of cyclic AMP (cAMP), follicular thyroglobulin (Tg) and free tri-iodothyronine (FT3) production. In contrast, free thyroxine levels increased in the medium of thyrocytes cultured as follicles. Small doses of the drugs did not affect thyrocyte production. The inhibiting effect of thiopental, midazolam and ketamine on Tg and FT3 production seems to result from the inhibition of cAMP production and 5′-deiodinase.
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ABSTRACT
Cis-diamminedichloroplatinum (II) (cisplatin) is a widely used anticancer drug which induces many sideeffects, but its action on the thyroid gland is still unknown. We have investigated the effects of this drug on human thyrocytes cultured in monolayers or in follicles and stimulated with 200 μU TSH/ml.
After 72h in culture, different concentrations of cisplatin (15, 30 and 75 μm) caused partial or total inhibition of cyclic AMP (cAMP), thyroglobulin (Tg) and tri-iodothyronine (T3) production, whereas thyroxine levels increased in the medium of thyrocytes cultured as follicles. Small doses of the drug did not affect thyrocyte production. Decreases in neutral-red uptake by thyroid cells and in intracellular lactate dehydrogenase, α-hydroxybutyryldehydrogenase and creatine phosphokinase activities were induced by 30 and 75 μm cisplatin.
These data show that high concentrations of cisplatin had a cytotoxic effect on thyrocytes. Cisplatin also induced inhibition of the production of cAMP, Tg and T3.
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ABSTRACT
We studied the lymphocyte-induced alterations in hormonal metabolism and the production of tumour necrosis factor α (TNF-α) during coculture of thyrocytes and autologous lymphocytes from 20 patients with Graves' disease and from five normal subjects. Thyroglobulin (Tg) mRNA was assessed by slot-blot analysis under TSH stimulation. Tg, tri-iodothyronine (T3) and cAMP secretion in the presence of TSH were measured by RIA after 3 or 5 days of coculture. TNF-α levels produced after 5 days incubation were also assayed in lymphocyte culture and coculture media.
Lymphocytes isolated from peripheral blood (PBLs) altered the production of Tg, T3 and cAMP in autologous thyrocytes. Intrathyroidal lymphocytes (ITLs) decreased Tg and cAMP secretion but had no effect on T3 secretion. The reductions in Tg and cAMP levels obtained with mechanically isolated ITLs (M-ITLs) were generally higher than those obtained with ITLs isolated by dispase (D-ITLs). No difference was seen between Graves' disease and normal cocultures. PBLs secreted large concentrations of TNF-α, larger than those obtained with M-ITLs whereas D-ITLs produced low amounts of this cytokine. In coculture, TNF-α levels were lower than those observed in lymphocyte culture. Significant correlations were obtained between TNF-α levels and the decrease in Tg, T3 and cAMP concentrations. The percentage of T lymphocytes was higher in PBLs and D-ITLs than in M-ITLs. B lymphocytes levels were higher in ITLs, especially M-ITLs, than in PBLs. TNF-α production by B lymphocytes was maximal in M-ITLs.
In conclusion, lymphocytes induced a decrease in hormonal thyroid metabolism when cocultured with autologous thyrocytes. These perturbations may be attributed, at least partly, to TNF-α secreted by lymphocytes. TNF-α interacts via the adenylate cyclase pathway of TSH signal transduction.
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We have investigated the in vitro expression of membrane and soluble intercellular adhesion molecule-1 (ICAM-1) by human thyroid cells from 20 patients with Graves' disease and 5 normal subjects. Membrane ICAM-1 was not detected by flow cytometry analysis in non-cultured thyrocytes from either normal or Graves' disease tissues. It appeared on thyroid cells after a 24-h culture in monolayers and showed a regular dose-dependent increase. The same results were obtained with soluble ICAM-1 (sICAM-1) in culture media from cells cultured in monolayers, vesicles or follicles. No change was obtained with different concentrations of fetal calf serum added to the media. Coculture of Graves' disease thyrocytes with autologous peripheral blood lymphocytes (PBL) or intrathyroidal lymphocytes (ITL) enhanced the expression of both membrane and sICAM-1 whatever the culture model. When normal thyrocytes were cocultured with PBL, sICAM-1 increased but with ITL sICAM-1 remained unchanged. High concentrations of gamma interferon induced an increase of both membrane and sICAM-1 in the three culture models. However the increases were greater with vesicles and follicles. Only sICAM-1 levels were raised with 0.1, 1 and 10 microM retinoic acid. These results suggest that ICAM-1 appears in culture, possibly due to mechanical effects such as adherence to plates and cell-to-cell contacts. Moreover, its expression is modulated by several factors such as cytokines or retinoic acid. Further investigations are needed to establish whether ICAM-1 is really involved in the pathogenesis of Graves' disease.
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ABSTRACT
We have studied the action of peripheral blood lymphocytes (PBLs) and intrathyroidal lymphocytes (ITLs) on the biochemical and hormonal metabolism of autologous thyrocytes cultured in follicles in a collagen gel. The production of tumour necrosis factor α (TNF-α) in culture was also measured. Thyroid tissues and lymphocytes were obtained from ten patients with Graves' disease and from five control subjects. Lymphocyte-induced cytotoxicity was evaluated in autologous thyrocytes cultured in a collagen gel by several tests: neutral red uptake, lactate dehydrogenase activity and glutathione level. Hormonal metabolism was assessed by evaluating tri-iodothyronine (T3) and total cAMP production under TSH stimulation. TNF-α levels were measured in supernatants after 5 days of coculture. PBLs altered biochemical metabolism, T3 synthesis and cAMP production in autologous thyroid follicles. These inhibitions were greater than those obtained with ITLs. No difference was seen between cells obtained from patients with Graves' disease and those from normal subjects. TNF-α levels secreted by PBLs were higher than those secreted by ITLs. The concentrations of this cytokine decreased in coculture. Significant correlations were observed between the decrease in biochemical and hormonal parameters and TNF-α levels. Exogenous TNF-α and high doses of interferon γ inhibited follicle metabolism, especially hormone secretion.
In conclusion, thyrocytes cultured in follicles provide a more sensitive model than monolayer cultures for analysis of lymphocyte-induced interactions. Lymphocytes gradually inhibit the biochemical and hormonal metabolism of autologous thyroid follicles depending on the isolation method. These alterations may be particularly attributed to TNF-α secreted by lymphocytes. The cytokine-induced inhibition of thyroid hormonal function apparently involves the adenylate cyclase system.
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ABSTRACT
We studied the hormonal secretion of a human mixed follicular and medullary carcinoma. Thyroglobulin (Tg) secretion, especially by large cells and sometimes by small ones, was visualized with immunoenzymatic staining. Calcitonin (CT) was produced by small spindle-shaped cells. Moreover, immunofluorescence double staining performed on the resected thyroid tissue showed the secretion of both Tg and CT in a small number of cells. The cells lost their hormonal secretion after 2 months of culture. Hormonal secretion was modulated by different additives in the medium. Tg secretion was induced when TSH was added to the culture medium; the maximal effect was produced with the addition of 1 mU TSH/ml and 1 μm cortisol, which potentiated the effect of TSH on Tg production. A durable Tg secretion was obtained by embedding the cells in Engelbretch—Hohn—Swarn (EHS) tumour matrix. The CT production was reinduced by the addition of 4 mm Ca2+, 1 μm glucagon and 1 μm cortisol to the culture medium. These findings show that different cells are found in a mixed follicular and medullary carcinoma, some of which can secrete both CT and Tg. They can remain differentiated for a long period after being embedded in EHS tumour matrix with Ca2+ and hormonal components.
