Glucocorticoid receptors in developing rat brain and liver

Dexamethasone receptors were measured by conventional equilibrium steroid binding studies in rat liver and brain cytosol, during late prenatal and postnatal development, Receptor binding could be detected in both cytosol preparations as early as the 17th day of gestation. Receptor levels in the cytosol from intact animals reached adult values by the 1st day after birth in both tissues. Using adrenalectomized animals an increase which reached adult values was observed during the first postnatal week for liver and the second postnatal week for brain. At physiological concentrations of endogenous glucocorticoids depletion of receptor from the cytosol of intact animals was minimal at postnatal day 1 and reached adult levels by day 7. chromatographie analysis in DEAE-Sephadex A50 minicolumns of unactivated and activated receptor constituents revealed the same pattern as that of adult animals. Glucocorticoid receptor complex from developing liver and brain was shown to be capable of binding to isolated adult liver nuclei after in vitro activation. However full capacity, for nuclear binding was observed in vivo, after injection of inducing doses of [³H]dexamethasone: By the end of the first week after birth adult nuclear binding capacity was observed in experiments in vivo while values peaked during the second week, in both tissues studied.     

Glucocorticoid regulation of glycerolphosphate dehydrogenase expression in the developing rat brain

Glucocorticoid regulation of glycerolphosphate dehydrogenase (GPDH) activity and gene expression in the developing rat brain appears complex throughout the postnatal developmental period and attains the adult pattern after the first month of life. GPDH enzyme activity is higher in the limbic system than in the cerebral cortex of intact young animals. Adrenalectomy of young rats, before the first month of life, does not affect GPDH enzyme activity in the brain areas mentioned above, while in the adult animals it results in a statistically significant decrease in activity. Furthermore, adult type glucocorticoid responsivity of GPDH enzyme activity is attained in the developing limbic system earlier — by day 40 of life — than in the cerebral cortex. During the first month of life, GPDH basal mRNA levels are increased in the absence of glucocorticoids, in both the limbic system and the cortex, in contrast to the effect of adrenalectomy in the adults, where GPDH mRNA levels are decreased in the absence of the adrenals. The observed pattern of glucocorticoid regulation of GPDH during development in the rat is discussed in relation to the possible existence of various levels of regulation of GPDH gene and enzyme activity.     

Salicylate-induced teratogenesis in the ferret

A single subcutaneous injection of 400 mg/kg sodium salicylate produced a high resorption rate on day 13 (91%) and on day 18 (66%) of gestation. Malformations were seen in the surviving fetuses. Pregnant ferrets injected with 250 mg/kg salicylate produced a lower resorption rate of between 31% and 43%. Malformations were seen in the surviving fetuses of animals injected with lower doses of sodium salicylate both at 13 and 18 days of gestation.Salicylate-induced teratogenicity at 400 mg/kg was compared with that produced in a closed colony of Wistar rats. The concentration of salicylate in whole blood (and serum) was determined after a single injection of 125 mg/kg or 400 mg/kg sodium salicylate. Although salicylate concentration in the blood in both species showed remarkable similarity at the doses tested and the times of sampling, the results indicated that the drug was far more embryo-toxic in ferrets than in rats. The inter-order variation in the embryotoxicity of sodium salicylate is such that it would be unwise to ignore its possible teratogenic activity in man.