GLUCOCORTICOID EFFECT UPON THYMIDINE KINASE IN DEVELOPING CEREBELLUM

Abstract

Glucocorticoids have been used in animal models and more recently in human studies as a means to accelerate neonatal lung maturation in order to prevent the respiratory distress syndrome in premature infants. Little attention has been paid to the possible effects of glucocorticoids upon developing organs other than lung. Recent studies of cortisol administration on DNA content in developing rat brain showed an early reduction as well as a permanent defecit in cerebellar DNA. In addition to confirming these findings, we have shown cortisol administration in the early neonatal period to have a profound effect on thymidine kinase, a salvage pathway enzyme for pyrimidine biosynthesis, in rat cerebellum during early development. Thymidine kinase normally peaks in activity in rat cerebellum at approximately 6 days of postnatal age and falls rapidly thereafter. With cortisol administration, enzyme activity is maximally suppressed at 6 days of age using both normal and undernourished controls. These findings suggest that neonatally administered glucocorticoids may have effects which are potentially detrimental to areas of the central nervous system which may be undergoing cell replication during the time the drug is administered. Thus the possible use of glucocorticoids for their salutary effects in the respiratory distress syndrome may necessitate consideration of any hazardous effects, however subtle, upon central nervous system development.