SummaryThymidine kinase activities, virtually all soluble in rat lung, liver, and small intestine, descreased abruptly late in gestation or immediately after birth. An injection of thyroxine delayed the fetal but not the neonatal changes in liver activity. An injection of cortisol decreased hepatic and pulmonary thymidine kinase activities in both fetal and neonatal rats but had little effect on the intestinal enzyme. Premature extrauterinization led to an earlier occurrence of the quantitative changes in thymidine kinase activity usually seen at term. Birth-associated changes included a rapid transitory increase in the hepatic enzyme and the virtual loss of intestinal thymidine kinase activity.In human tissues, the soluble thymidine kinase in liver remained high between the 11th and 22nd wk of gestation whereas the particulate enzyme, the predominant form in adult liver, rose in the second half of gestation and reached adult levels a t birth. In human lung, the soluble enzyme started to decrease by the 16th gestational wk, whereas the particulate thymidiie kinase reached the higher adult levels late in gestation. Thymidine kinase in adult human tissues was predominantly particulate. rapidly in the adult but also have hematopoietic potential, e.g., spleen, thymus, and bone marrow (10, 33). The implication of these observations prompted us to explore the developmental changes in the thymidine kinase activities in rat liver after the time when that organ has ceased to contribute significantly to hematopoiesis and to determine if the normal postnatal decreases in thymidine kinase are as abrupt in rat tissues that do not have hematopoietic potential (e.g., small intestine and lung). We also investigated the effects of the process of birth per se (normal or premature delivery) on the activities of this enzyme during the first postnatal day and compared the effects of a cortisol or thyroxine injection on the enzyme in liver, lung, and small intestine before and after birth. To test whether the developmental changes in the thymidine kinase activities in rat tissues provide a model for maturational events in this enzyme in human tissues. we also measured the thymidine kinase in livers and lungs of electively aborted fetuses and from autopsy (neonates) and surgical biopsy specimens of adult humans. The major portion of thymidine kinase in the rat was restricted to the soluble fraction of tissues (21, 33). It has previously been shown that much of the enzyme in adult human tissues is associated with particles (especiafiy mitochondria) (21,26,36) and that the properties of the Speculation cytosolic and particulate form of the enzyme differ (23, 26, 32, 34, The postnatal accumulation of soluble thymidine kinase in rat 36). We the changes in the of liver, lung, and small intestine may be associated new DNA the soluble and particle-bound thymidine kinase in human liver, synthesis preliminary to the emergence of ontogenica~~y intestine, and lung. Our results demonstrate that their developenzyme clusters a t discrete intervals ...