Effect of thyroxine and prednisolone and the exogenous RNA induced by them on the proliferation of cells

As demonstrate experiments performed on cells of the primary culture of the newborn rat kidney, injection of thyroxin stimulates, and addition of prednisolone inhibits the proliferative activity of the cells in the culture. At a combined and simultaneous administration of these two hormones, as well as at injection of thyroxin 2 h before prednisolone, the thyroxin program, stimulating the cell proliferation is expressed. When thyroxin is administered 2 h after prednisolone, during first 12 h the prednisolone program is expressed, and then the proliferative activity of the culture returns to the initial level. At the cooperative action of oppositely directed factors for realization of the cell proliferative program, an essential role play the time factor and lag-period duration for each of the hormones interacting. Exogenic RNAs, obtained from the kidneys of the rats, to whom thyroxin or prednisolone have been injected, when they (RNAs) are injected into the culture, they produce effects, similar to those that are noted at injecting these hormones into the incubation medium. Thus, injection of the hormones to rats, results in formation, by the cells of the organ, induced RNAs, capable to transfer a hormonal signal and produce a hormone-like effect at regulation of the proliferative activity of the cell culture in the obtained exogenic RNA from the organ-donor.     

Reduction in the latent period of the response to thyroxin by tadpole tail discs fused to discs pretreated with thyroxin.

It has been previously shown that tissue blocks prepared from the tail fins of tadpoles (Rana pipiens) survive in vitro for several weeks and respond to thyroxin by shrinkage after a latent period of four or more days (20°C). It has been postulated that this shrinkage corresponds to that of normal tail tissue during metamorphic climax. The long latent period of thyroid action is presumed to depend upon the time required to form the necessary cellular or biochemical intermediates. If such intermediates are activated by thyroxin in the amphibian tail tissue, it may be possible to shorten the latent period of the thyroxin response of fin tissue by fusing untreated blocks to blocks previously treated with thyroxin. Experiments are reported here in which tail fin blocks obtained from tadpoles previously immersed in thyroxin for 3 days were docked to recipient blocks not exposed to this hormone. Such recipient tissues responded with characteristic resorptive activity within 24 hr, instead of the minimum of 4 days required by control tissues exposed directly to thyroxin. It is inferred that some component other than thyroxin which is active in inducing resorption is transmitted from the treated to the untreated block. Presumably, this is a product normally present late in the latent period of thyroxin action.     

Concanavalin A as a peripherally acting inhibitor of thyroxin-mediated metamorphosis in amphibians

Stimulated by reports that Concanavalin A (Con A), a plant protein and lectin from jack bean, has an inhibitory effect on thyroid activation induced by thyrotropin, we set out to test whether Con A inhibits thyroid action on hormone-sensitive target tissues in amphibians. We noted that premetamorphic tadpoles injected with 0.15 ml of thyroxin (T₄ 0.24 μM) responded by accelerating metamorphic change as indicated by precocious disappearance of the tail, and appreciable growth of the hind limbs and changes in mouth-part morphology. Tadpoles given an injection of thyroxin immediately followed by an injection of Con A (9.6 μM) showed no such metamorphic changes. In the second series of experiments tail fin discs obtained from premetamorphic tadpoles when placed in cultures supplemented with T₄ (0.24 μM) had completely shrunk within 96 hr. Tail fin discs that were raised in vitro in medium containing Con A as well as thyroxin failed to regress. In the third series of experiments tail discs were initially cultured in medium containing thyroxin and transferred within 48 hr to medium containing Con A. When Con A was added after this 48-hr exposure to thyroxin it was no longer effective in preventing tail fin disc resorption. We conclude tentatively (1) that Con A is a peripheral inhibitor of thyroxin and (2) this it somehow binds to the tissue or interacts with thyroxin rendering it ineffective before the hormone has a chance to act. The significance of finding a peripherally active inhibitor of thyroid hormone for studies of mechanism of action of this hormone on development and differentiation of hormone-sensitive target structures is obvious.     

Effect of thyroxine in the G0 stage of the cell cycle on the yield of chromosome aberrations in rat hepatocytes and human lymphocytes after X-irradiation

A study was made of the mechanism of a modifying action of thyroxin (T4) on the chromosome integrity after the application thereof in vivo and in vitro following a single whole-body exposure to X-radiation with a dose of 2.19 Gy. It is concluded that T4 influences the quantity of cells with chromosome aberrations stimulating the recovery of the chromosome integrity: the stimulation can be brought about at the G0 stage of the cell cycle as a result of the direct effect of the hormone on a cell.