Aspartate aminotransferase in fat tissues: changes with growth and hormones.
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Biomedical subjects
Publications and source records attributed to O Greengard.
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Livers of normal rats are devoid of catalytically or immunochemically reactive tryptophan oxygenase (EC 1.13.1.12) up to the 10th postnatal day; the enzyme reaches adult concentrations on about the twentieth day. Premature tryptophan oxygenase synthesis can be evoked in 4-day-old rats: if an injection of glucocorticoid is followed, a day later, by an injection of tryptophan, adult levels of tryptophan oxygenase activity and antigen content can be attained within 5 hr. The prematurely evoked tryptophan oxygenase is degraded in about 2 days, but the preparatory action of the glucocorticoid is longlasting. Even 4 days later, an injection of tryptophan can evoke significant enzyme formation. Actinomycin D, injected together with or 12 hr before the tryptophan, is not inhibitory, but if injected with the glucocorticoid it prevents enzyme formation upon later injection of tryptophan. The observations suggest that appearance of the new enzyme in developing tissue results from the sequential action of more than one stimulus and that the potentiality for its transcription may develop long before its actual synthesis.
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1. The administration of glucagon, cAMP [adenosine 3',5'-(cyclic)-monophosphate], BcAMP [6-N-2'-O-dibutyryladenosine 3',5'-(cyclic)-monophosphate] or adrenaline to foetal rats during the last 2 days of gestation evoked the appearance of tyrosine aminotransferase and enhanced the accumulation of glucose 6-phosphatase in the liver. In foetuses 1-2 days younger only BcAMP was effective. After birth liver glucose 6-phosphatase no longer responds to glucagon or BcAMP. Tyrosine aminotransferase is still inducible by these agents in 2-day-old rats, but not in 50-day-old rats. After adrenalectomy of adults glucagon or BcAMP can enhance the induction of the enzyme by hydrocortisone. The results indicate that the ability to synthesize tyrosine aminotransferase and glucose 6-phosphatase when exposed to cAMP develops sooner than the ability to respond to glucagon with an increase in the concentration of cAMP; the responsiveness of enzymes to different hormones changes with age. A scheme illustrating the sequential development of competence in regulating the level of an enzyme is presented. 2. Actinomycin inhibited the effects of glucagon and BcAMP on liver tyrosine aminotransferase and glucose 6-phosphatase in foetal rats. Growth hormone, insulin and hydrocortisone did not enhance the formation of these enzymes. 3. The time-course of accumulation of glucose 6-phosphatase in the kidney is different from that in the liver. Hormones that increase the accumulation in foetal liver do not do so in the kidney of the same foetus or in the livers of postnatal rats.
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