Influence of certain hormones on nucleic acids and metabolism by lymphocytes

In the present investigation the uptake and prolonged retention of adenine-8-C-14 by lymphatic tissue of mice was demonstrated. The experiments bring support to the idea that the nucleic acids of dead lymphocytes are re-utilized during heteroplastic lymphocytopoiesis. Tumor tissue has been shown to retain less of the radioactive labeled nucleic acids than normal tissue, and this is interpreted as an impairment of the reticulo-endothelial system involved in heteroplastic lymphocytopoiesis. Cortisol causes a depletion of nucleic acids as well as an inhibition of the biosynthesis of nucleic acids in the intact animal. Conclusive evidence has therefore been presented in support of earlier histological findings that cortisol not only destroys cells but also inhibits cell proliferation. ACTH in the intact animal has an effect similar to cortisol, probably due to its known function as an adrenal cortical stimulating agent. Adrenalectomy does not cause a general increase in nucleic acid biosynthesis in the lymphatic tissue. In fact, our findings imply that the absence of the adrenals will cause an inhibition particularly of the RNA biosynthesis. It is concluded that adrenal cortical hormones might stimulate certain aspects of nucleic acid metabolism. In the absence of the adrenals this stimulatory effect of cortical hormones was more conclusively demonstrated. Cortisol in the adrenalectomized animals inhibits the biosynthesis of DNA in lymph node and thymus but will not markedly stimulate the adenine-8-C-14 incorporation by RNA of these tissues as well as that by both nucleic acids of the spleen. This is considered as conclusive evidence that adrenal cortical hormones do stimulate certain aspects of nucleic acid biosynthesis. A profound extra-adrenal effect of ACTH was demonstrated in adrenalectomized animals. ACTH will markedly stimulate biosynthesis of both RNA and DNA in all lymphatic tissues studied. Glycine-C-14 was not similarly affect by ACTH in the adrenalectomized animal. Support for the idea that glycine follows a different pathway of incorporation than that of adenine was therefore obtained. In the tumor bearing animals cortisol has a less profound effect that in the normal intact animals. Cortisol inhibited the biosynthesis of RNA in the tumor but clearly enhanced the biosynthesis in both nucleic acids in spleen and thymus. It is speculated that since these effects resemble the effects of cortisol in adrenalextomized animals, the tumor bearing animal might have an adrenal cortical insufficiency. The implications of these findings and interpretations have been further discussed.