Max Cake

The stimulatory or inhibitory effects of numerous hormones are required for many perinatal developmental events that are essential for postnatal survival. These developmental processes include the acquisition of gluconeogenesis, amino acid catabolism, and urea biosynthetic capacity in the neonatal liver; perinatal lung maturation; and alterations to digestive enzyme capabilities upon weaning. Much of our understanding of the mechanisms underlying regulation of the relevant biochemical pathways stems from the cloning of critical genes. Transcription factor motifs and enhancer sequences have been identified in their promoter regions, which are involved in regulating their expression and their perinatal appearance. Although enhanced expression of these genes, which leads to improved metabolic capacity and versatility of the tissues, is primarily the result of de novo transcription, there is compelling evidence that posttranscriptional mechanisms can also contribute.

Glucocorticoids are known to have profound effects on glucose and protein metabolism as a result of their ability to regulate metabolic processes in various tissues of the adult. In addition to these effects in the adult, glucocorticoids have been implicated as important regulators in the development of several different tissues (1-5). In a number of these systems shown to be glucocorticoid sensitive it has been found that insulin augments the response. In the liver, both hormones are required to enhance glycogen synthetase activity resulting in an increased deposition of glycogen (6). Differentiation of mammary epithelial cells in vitro and the subsequent synthesis of casein and a-lactalbumin have been shown to be dependent on the simultaneous presence of insulin, glucocorticoids and prolactin (4,7). Insulin and glucocorticoids have also been shown to act synergistically in the induction of glutamine synthetase in 3T3-L1 adipocytes (8) and of tyrosine aminotrans-ferase in HTC cells (9,10)…

The administration of glucocorticoids fails to induce tyrosine aminotransferase activity in fetal rat liver in utero but causes a marked increase in the activity of this enzyme in postnatal rats. In adult animals, this increase has been shown to be the result of the production of enhanced amounts of mRNA for tyrosine aminotransferase, leading to an increase in the rate of synthesis of the enzyme. The lack of steroid response in utero is not due to an impairment in uptake of the hormone by fetal liver, nor is it due to a lack of glucocorticoid receptors, as both cytoplasmic and nuclear receptors have been detected in fetal liver. In studies with cultured fetal hepatocytes, dexamethasone is able to induce the enzyme but the presence of insulin prevents this induction at a post-transcriptional step. It is therefore proposed, that glucocorticoids are active at the transcriptional level in fetal liver but that a high concentration of insulin inhibits some post-transcriptional process, thus preventing the synthesis of tyrosine aminotransferase (TAT).