Role of adrenaline and cyclic AMP in appearance of tyrosine aminotransferase in perinatal rat liver

Abstract

1. Adrenaline increased hepatic tyrosine aminotransferase activity when injected into foetal rats or 2-day-old rats. 2. The inhibition of the postnatal increase in tyrosine aminotransferase activity which occurred in adrenalectomized newborn rats rapidly overcome by injection of adrenaline or dibutyryl cyclic AMP. 3. The effects of adrenaline or dibutyryl cyclic AMP on the tyrosine aminotransferase activity in foetal, adrenalectomized newborn and 2-day-old rats could be partially or completely blocked by prior treatment with actinomycin D. 4. Dibutyryl cyclic AMP induced tyrosine aminotransferase activity in hepatocytes cultured from 15-day foetal rats in glucocorticoid-free medium. 5. Actinomycin D at 0.2 microgram/ml in the culture medium completely prevented the induction of tyrosine aminotransferase activity by dibutyryl cyclic AMP in cultured cells. 6. The results suggest that adrenaline and cyclic AMP stimulate a transcriptional event during induction of tyrosine aminotransferase in perinatal liver.

Hormonal regulation of TSE1-repressed genes: evidence for multiple genetic controls in extinction.

“…Furthermore, humoral agents modulate expression of these genes in similar ways: both glucocorticoids and cyclic AMP (cAMP) induce PEPCK (29), TAT (30), and AS (22) expression in liver. Other studies suggest that cAMP stimulates the initial synthesis of PEPCK shortly after birth (28), and both glucocorticoids and cAMP have been implicated in the postnatal induction of TAT (11,12,33).…”

“…The first such locus, tissuespecific extinguisher 1 (TSEI), is a discrete genetic entity that resides on mouse chromosome 11 and human chromosome 17. TSEI extinguishes tyrosine aminotransferase (TAT) (13), phosphoenolpyruvate carboxykinase (PEPCK) (15), and argininosuccinate synthetase (AS) (this report) expression in trans, but it has no effect on expression of most other liver genes.…”

On the mechanism of a radiation-induced change in enzymic differentiation during development

“…This system is of interest since one of its components, adenylate cyclase synthesizing cyclic AMP, is the site of action of adrenaline and glucagon, the major signals for the appearance of tyrosine aminotransferase in the liver at birth. Participation of cyclic AMP in tyrosine aminotransferase synthesis is described in [11,15,18], and a mechanism for its action is discussed in [8,9,23]. Table 2 shows the activity of the enzymes involved in cyclic AMP metabolism in the liver of newborn rats after preirradiation of the embryo (0.5 Gy) on day 9 p.c.…”

“…Thus, for example, there is a rise in the activity of the enzymes regulating gluconeogenesis, including glucose-6-phosphatase and tyrosine aminotransferase [3,7,15], which results from de novo synthesis [11,18]. The mechanisms underlying changes in enzymic differentiation during development are obscure.…”

“…For instance, the appearance of glucose-6-phosphatase follows an increase in thyroxine secretion by the fetus [17]. Adrenaline and glucagon are the inductors of tyrosine aminotransferase synthesis during the first hours after birth [11,14,16]. The high radiosensitivity of the developing organism [24,25] has prompted us to study the effect of ionizing radiation on enzymic differentiation.…”