Tumor necrosis factor-α is assumed to be an important mediator in thyroid autoimmunity. In the present study we have shown that human thyrocytes possess a single specific binding site for recombinant tumor necrosis factor-α with an average of 9,300 receptors/cell (Kd = 1.9 · 10−10 mol). The effects of the cytokine on thyroid cell proliferation were assessed by 3H-thymidine uptake as well as by the protein and DNA content of cell monolayers. Low dose tumor necrosis factor-α resulted in a moderate stimulation of cell proliferation with an increase of 3H-thymidine incorporation from 44,613±7,989 cpm under basal conditions to 63,326±6,822 cpm after 100 U/l tumor necrosis factor-α (p <0.01). Higher doses of the cytokine were less effective. On average, bTSH stimulated cAMP production of human thyrocytes was significantly augmented after preincubation with recombinant tumor necrosis factor-α. The maximum effect was observed after 1,000 U/l tumor necrosis factor-α (281.5±107.0 vs 114.5±33.6 fmol cAMP/μg protein under basal conditions; p<0.05), whereas higher doses of the cytokine were again less effective. This phenomenon could at least partly be explained by a cytokine-mediated downregulation of tumor necrosis factor-α binding. We conclude that in vitro tumor necrosis factor-α modulates in addition to its well known synergistic effect on interferon-γ induced HLA class II expression the function and proliferation of human thyroid follicular cells as well. These effects are mediated via specific cell surface receptors.
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Ulrich Deuss, Massimo Buscema, Heike Schumacher, and Werner Winkelmann
Bruno Allolio, Martin Oremus, Martin Reincke, Hans-Jörg Schaeffer, Werner Winkelmann, Georg Heck, and Heinrich M Schulte
Allolio B, Oremus M, Reincke M, Schaeffer H-J, Winkelmann W, Heck G, Schulte HM. High-dose progesterone infusion in healthy males: evidence against antiglucocorticoid activity of progesterone. Eur J Endocrinol 1995;133:696–700. ISSN 0804–4643
High concentrations of unbound cortisol in late pregnancy have been explained by the antiglucocorticoid activity of high progesterone levels. To further test this hypothesis we studied the effect of high-dose progesterone on baseline and corticotrophin-releasing hormone (CRH)-induced hormone secretion in humans. In a double-blind crossover study eight healthy male volunteers received either progesterone (0.714 mg · kg−1 · h−1 for 60 min followed by a dose of 0.45 mg · kg−1 · h−1 over a total infusion time of 315 min) or vehicle as a continuous intravenous infusion. At 210 min a CRH test (0.1 μg/kg body weight as bolus iv) was performed. Within 30 min after the start of progesterone administration the serum progesterone level increased to 454 ± 31 nmol/l and remained in the range of third trimester pregnancy concentrations throughout the infusion period. During vehicle infusion the progesterone level remained in the normal range for healthy males and demonstrated a small but significant increase after CRH (1.52 ± 0.23 vs 0.74 ± 0.14 nmol/l; p < 0.01). However, baseline and CRH-stimulated serum cortisol and plasma adrenocorticotrophic hormone remained unaffected by high-dose progesterone. Moreover, unbound salivary cortisol also was not affected by progesterone, suggesting that there is no significant competition for transcortin binding sites. In conclusion, no antiglucorticoid activity was found after short-term administration of progesterone in males. These findings cast doubts on the concept that the alterations of the pituitary–adrenal axis in late pregnancy are induced by the antiglucocorticoid activity of high progesterone concentrations.
Bruno Allolio, Medizinische Universitätsklinik Würzburg, Josef-Schneider-Str. 2, 97080 Würzburg, Germany