The production and growth regulatory activity of transforming growth factor f were studied in human thyroid tissue. As estimated by its mRNA expression in fresh tissue samples, transforming growth factor , was produced in normal and in diseased thyroid glands. Transforming growth factor , mRNA was mainly produced by thyroid follicular cells and in lesser quantities by thyroid infiltrating mononuclear cells. The concentrations of transforming growth factor #t mRNA were lower in iodine-deficient nontoxic goiter than in Graves' disease and normal thyroid tissue. Transforming growth factor ft protein secretion by cultured thyroid follicular cells was also low in nontoxic goiter, but could be increased by addition of sodium iodide (10 ,uM) to the culture medium. Recombinant transforming growth factor # did not affect basal tritiated thymidine incorporation in cultured thyroid follicular cells, but inhibited, at a concentration of 10 ng/ml, the growth stimulatory influence of insulin-like growth factor I, epidermal growth factor, transforming growth factor a, TSH, and partly that of normal human serum on cultured thyroid follicular cells. This inhibition was greater in Graves' disease than in nontoxic goiter. These results suggest that transforming growth factor ,B may act as an autocrine growth inhibitor on thyroid follicular cells.

In permanent night shift workers the impact of environmental time cues on the circadian system is conflicting. Rhythm adjustments to the nocturnal work schedule have been described, and their significance for tolerance to shift work is under discussion. Reports concerning the effect of this work situation on the setting of the endogenous clock are, however, inconsistent. We examined nine healthy young male permanent shift workers with high work satisfaction at the end of a week on night work and seven male controls with normal diurnal working hours. All subjects were admitted to a research facility for 28 h, and blood was collected with a continuous-withdrawal pump in portions taken hourly for the estimation of the circadian melatonin (MT) and cortisol secretion pattern. One control did not exhibit a circadian secretion pattern. When compared with the other controls (n = 6), all except one of the shift workers showed no difference in the phase or phase relationship of their hormonal profiles. In the shift workers, a minor trend toward elevation of the MT amplitude and an increase in two indicators for the amount of MT secreted were noticed. One individual displayed inverse hormone rhythms with an undisturbed phase relationship of MT and cortisol and inconspicuous hormone amplitudes. He showed, however, an inverse day-night rhythm in his private life, too. The data collected suggest that even permanent night workers with a high degree of work satisfaction do not usually lose the diurnal orientation of their endogenous clock. Factors other than reorientation of the circadian system may be more important for high tolerance to shift work.

Plasma concentrations of proteins secreted by the liver (prealbumin, haptoglobin, transferrin, ceruloplasmin, alpha 1-antitrypsin, antithrombin III, and T4-binding globulin) and proteins mainly derived from endothelium [fibronectin, angiotensin-converting enzyme (ACE), and factor VIII-related antigen (F VIII R:Ag)] were measured in 27 hyperthyroid and 30 normal women. Significantly increased plasma concentrations (P less than 0.01) of endothelium-associated proteins, including fibronectin, ACE, and F VIII R:Ag, were found in hyperthyroid patients, while levels of proteins of primarily hepatic origin were normal. To determine whether the increase in endothelium-associated proteins in hyperthyroidism was directly related to elevated thyroid hormone levels, seven normal women were given T3 (25 micrograms, three times daily) for 2 weeks. These women had a consistent rise (P less than 0.05) in plasma concentrations of fibronectin, ACE, F VIII R:Ag, and tissue plasminogen activator. The rise in endothelium-associated proteins persisted for 10 days after cessation of T3. Plasma concentrations of hepatically synthesized proteins did not change. We conclude that thyroid hormone action either promotes endothelial protein synthesis or impairs its clearance.

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In order to define whether CD4+ T cells from autoimmune and non-autoimmune thyroid tissue could be classified according to their mediator production, lymphokine production was studied in 63 thyroid-derived CD4+ T-cell clones from four patients with Graves' disease, one with Hashimoto's thyroiditis, and one with non-toxic goitre (9-12 clones per patient). The production of interleukin 2 (IL-2), gamma interferon (IFN-gamma), tumour necrosis factor alpha (TNF-alpha), lymphotoxin (LT), interleukin 6 (IL-6) and transforming growth factor beta (TGF-beta) was assessed at the mRNA level by slot-blot analysis in unstimulated clones as well as after activation with monoclonal anti-CD3 (OKT3) and IL-2. No lymphokine production was found in unstimulated clones, whereas 56% of the clones produced all six lymphokines simultaneously after stimulation. In the remaining 44% usually not more than one lymphokine was missing from the complete panel. Lymphokine mRNA concentrations varied between different clones and different patients, but, in this small sample, not between the diseases from which the clones were originated. There was a significant correlation between IL-6, LT, and IL-2 mRNA levels and T-cell helper function, which was estimated by the stimulation of thyroid microsomal autoantibody production using autologous peripheral B cells. TGF-beta and IFN-gamma mRNA expression was unrelated to T-cell help. The results demonstrate that intrathyroid T cells from autoimmune and non-autoimmune thyroid disorders cannot be classified according to their lymphokine production, unlike some results with in vitro-induced mouse T-cell clones, where two populations, Th1 and Th2, have been described. Single T cells are capable of producing a whole panel of lymphokines and thus are capable of triggering a multitude of different processes.