The Relation of the Teratogenic Action of Cortisone to Liver Transaminase Activity

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Abstract
A study of the effects of cortisone on fetal and mother liver GOT [glutamic-oxalacetic transaminase] and GPT [glutamic-pyruvic transaminase] transaminase activity and its relation to congenital anomalies, in particular, cleft palate. Primiparous CFW mice, seven weeks old (about 23-25 gnu), from Carworth Farms were used. A specific mating procedure is described which aided in increasing the number of pregnancies. To reduce the number of resorptions produced by cortisone administration, the animals were placed on a high fat ration subsequent to pregnancy. Administration of cortisone, in addition to cleft palate, produced spinal deformities and hydrocephaly. Treatment with buffer produced 1.3% cleft palate offspring as compared to 0.5% in the untreated mother and 88% in the cortisone-treated pregnant mouse. No fetal anomalies were observed, other than the small number of cleft palates in the untreated group. There appeared to be a direct relation between the fetal weights and the per cent of the fetuses from each mother which were fused. The non-pregnant animals had a significantly higher GOT and GPT activity than their pregnant sisters. There was no difference in the transaminase activity in the mother and fetal livers between the untreated or buffer-treated pregnant animals, except for a higher GPT activity in the mother liver of the untreated pregnant group. Mothers bearing all cleft palate offspring in the cortisone-treated group had a higher GPT activity than the controls with fused palate offspring. Within the cortisone-treated group those mothers bearing all cleft palate offspring had a higher mean GPT activity than those bearing some fused fetuses. The livers of the cleft palate-bear ing fetuses of the cortisone-treated group had a higher GOT activity than those of the fused controls. There appears to be a relation between the fetal liver GOT activity and the per cent of resorption in each mother. The greater the per cent of resorption, the higher the GOT activity. The possible mechanism is discussed. No correlation could be found between the mother or fetal liver GOT or GPT activity and the fetal weight. The implications of this study are discussed. It appears likely that transaminase activity may be correlated not only with cortisone administration but also with the presence or absence of cleft palate. Further work is required before conclusions could be drawn with respect to other deformities.

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