Development of tyrosine aminotransferase in perinatal rat liver: Changes in functional messenger RNA and the role of inducing hormones

Abstract

Expression of the hepatic enzyme tyrosine aminotransferase was analyzed in the perinatal period of development in the rat, when this expression undergoes significant changes associated with hepatocyte differentiation. In late prenatal liver both enzyme and functional mRNA gene products are present at levels 10- to 15-fold below those in the fully differentiated adult liver. This low level of expression in fetal liver is refractory to induction by glucocorticoids, but both gene products are increased to a limited extent by cyclic AMP. This induction by cyclic AMP (cAMP) does not confer glucocorticoid-responsiveness on expression. By 3 hr after birth both functional mRNA and enzyme levels are significantly increased, an increase which continues until a peak is reached at 12 hr that is appreciably above the adult levels. Both gene products then decline until adult levels are reached by 24 hr. The postnatal shift in aminotransferase expression is accompanied by acquisition of the capacity to respond to glucocorticoids. Treatment of newborns with an antiglucocorticoid steroid or with glucose suppresses the postnatal overshoot of expression, but neither treatment affects the increase from fetal to adult levels of expression. The results indicate that prior to birth, expression of the aminotransferase gene is partially repressed, a repression that is lifted essentially immediately upon birth. The hormones capable of inducing aminotransferase synthesis have no apparent necessary role in this process.

The glucocorticoid hormone signal transduction pathway in mice homozygous for chromosomal deletions causing failure of cell type-specific inducible gene expression.

“…Significantly, inducible expression of the particular target genes affected by the lethal albino deletions becomes apparent in wild-type mice only around and after the time of birth while the same target genes are refractory to glucocorticoid induction in the normal fetal liver (17). Possible mechanisms responsible for the perinatal development of the required competence include those of chromatin changes in the enhancer regions of these genes preceding the ability of the receptor-hormone complex to bind to the glucocorticoidresponsive element (1).…”

Isolated Small Rat Hepatocytes Express both Annexin III and Terminal Differentiated Hepatocyte Markers, Tyrosine Aminotransferase and Tryptophan Oxygenase, at the mRNA Level

“…16,19,20) TO expression is also virtually absent in the fetus; the accumulation of mRNA is followed by an increase in enzyme activity 14 d after birth, when the transcription of the gene is activated. 17,18,21,22) On the other hand, albumin mRNA expression has been detected in rat embryo on gestational day 9.5-10.5.…”

Hepatic differentiation induced by oncostatin M attenuates fetal liver hematopoiesis

“…In contrast, the embryonic liver has much less metabolic activity and, rather, functions as a hematopoietic microenvironment (1)(2)(3)(4). Increasing evidence indicate that hematopoietic stem cells (HSCs) originating from the aorta-gonad-mesonephros (AGM) region migrate to the fetal liver to generate numerous definitive hematopoietic cells.…”