Transcriptional regulation of hippocampal 5-HT1a receptors by corticosteroid hormones.
5-HT1a receptors in the hippocampus play a critical role in modulating limbic system output. The activity and level of 5-HT1a receptors are modulated by glucocorticoid levels. The present study was undertaken to test the hypothesis that glucocorticoids attenuate the transcriptional activity of the 5-HT1a receptor gene. Using in situ hybridization and RNase protection assays, we observed a substantial increase in 5-HT1a mRNA expression after adrenalectomy in the same hippocampal regions in which 5-HT1a binding sites are increased. This increase in 5-HT1a mRNA expression occurs as early as 1 h after adrenalectomy and precedes the increase in receptor binding sites. Further in situ hybridization analysis showed that 5-HT1a mRNA is increased within individual hippocampal cells after adrenalectomy. Administration of dexamethasone completely prevents the adrenalectomy-induced elevation in hippocampal 5-HT1a receptor mRNA. Nuclear run-on assays showed that the rate of transcription of 5-HT1a mRNA after adrenalectomy increased 70% above the rate from control preparations and could be reduced to basal levels by the administration of dexamethasone. Adrenalectomy did not cause an increase in functional coupling of 5-HT1a receptors to adenylyl cyclase or phospholipase C. These results suggest that transcription of hippocampal 5-HT1a receptor mRNA is under negative regulation by corticosteroid hormones.
Zhong
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Nancy Pritzker Laboratory of Developmental and Molecular Neurobiology, Stanford University Medical Center, CA 94305-5485, USA.
Ciaranello
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D000315:Adrenalectomy; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism*; D007016:Hypophysectomy; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000145:classification / Q000378:metabolism*; D013997:Time Factors; D014018:Tissue Distribution; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology*
D005938:Glucocorticoids; D012333:RNA, Messenger; D011985:Receptors, Serotonin; D003907:Dexamethasone