Brain glucocorticoid receptors and their role in behavioural teratogenicity of synthetic glucocorticoids.
The distribution of glucocorticoid receptors (GR) in rat brain during development (postnatal days 3-16) was investigated and the prevalence of GR number was found in the cerebellum, the fastest growing part of perinatal brain. Dexamethasone (D) administration (0.04-3 mg . kg-1 s.c.) in 7-day-old rats induced dose-dependent depletion of brain cytosol GR with a 70% depletion after the smallest dose. Long-term effects of this GR mediated insult (D 1.0 and 0.2 mg . kg-1 s.c.) manifested themselves in adult rats as structural and biochemical brain deviations (especially in the cerebellum and hippocampus), behavioural abnormalities and reproduction disturbances. These sequels were detectable after D doses equal to clinical dosage in obstetrics and neonatology (0.2-0.6 mg . kg-1).
D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000367:Age Factors; D000818:Animals; D001921:Brain / Q000254:growth & development; D001923:Brain Chemistry; D002531:Cerebellum / Q000002:abnormalities / Q000032:analysis / Q000254:growth & development; D003907:Dexamethasone / Q000633:toxicity*; D005260:Female; D006624:Hippocampus / Q000002:abnormalities / Q000032:analysis / Q000254:growth & development; D006801:Humans; D006948:Hyperkinesis / Q000139:chemically induced* / Q000378:metabolism; D007859:Learning Disabilities / Q000139:chemically induced* / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000502:physiology*
D011965:Receptors, Glucocorticoid; D003907:Dexamethasone