Transforming growth factor-beta1 mRNA decreases in brain in response to glucocorticoid treatment of adrenalectomized rats.
Transforming growth factor-beta1 (TGF-beta1) was cloned from a rat hippocampal cDNA library by differential screening as a mRNA that was decreased by corticosterone (CORT) treatment. CORT responses in adult brain were investigated using a cRNA probe directed against the region of the TGF-beta1 transcript coding for the mature processed polypeptide. Hippocampal TGF-beta1 mRNA decreased 30% in rats treated with CORT (10 mg/day for 4 days) compared with adrenalectomized (ADX) controls; GAP-43 mRNA did not change in replicate samples. Hippocampal TGF-beta1 mRNA (2.5 kb) decreased 35 and 40% after 2 h of treatment with 1 and 10 mg CORT, respectively. The specific receptor agonist, RU 28362, decreased TGF-beta1 mRNA in hippocampus to a greater extent than CORT, aldosterone, or dihydrotestosterone, indicating that the response is mediated by type II glucocorticoid receptors. TGF-beta1 mRNA also decreased 20 to 50% in response to CORT in hypothalamus, cerebellum, striatum, and cortex, when compared with ADX controls. Finally, TGF-beta1 mRNA in cortex increased 20% at 3 days post-ADX compared with intact controls, which were similar to CORT-replaced rats. These results suggest that TGF-beta1-regulated actions in brain are subject to inhibitory control by glucocorticoids.
Nichols
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Division of Neurogerontology in the Andrus Gerontology Center and Department of Biological Sciences, University of Southern California, Los Angeles, California 90089-0191, USA.
Finch
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