The modulation of cyclic AMP dependent neurosteroidogenesis was studied in minces prepared from the cerebral cortex of adult rat. Forskolin or dibutyryl-cyclic AMP enhanced pregnenolone and progesterone production in a time and dose-dependent manner. The forskolin effect was mimicked by the cyclic AMP phosphodiesterase inhibitor isobutyl-methyl-xanthine, but not by the adenylate cyclase inactive forskolin analogue 1,9,dideoxy-forskolin. 4'-Chloro-diazepam, a high affinity ligand for the mitochondrial diazepam binding inhibitor (DBI) receptor, also elicited a time dependent increase in steroidogenesis. The forskolin and the 4'-chloro-diazepam stimulated pregnenolone increase was prevented by preexposing the rat brain cortical minces to 1-(2-chlorophenyl)-N-methyl-N-(1-methyl-propyl)-3-isoquinoline carboxamide (PK 11195), a high affinity ligand for the mitochondrial DBI receptor endowed with antagonistic properties. The protein synthesis inhibitor cycloheximide prevented the forskolin and 4'-chloro-diazepam stimulation of pregnenolone formation. In brain cortical minces of adrenalectomised/orchiectomised rats dibutyryl-cyclic AMP increased both pregnenolone and progesterone formation, while forskolin only increased progesterone. These data show that cyclic AMP enhances brain steroidogenesis by acting on a labile protein substrate which interacts with the mitochondrial DBI receptor.
Roscetti, G., Ambrosio, C., Trabucchi, M., Massotti, M., & Barbaccia, M.L. (1994). Modulatory mechanisms of cyclic AMP-stimulated steroid content in rat brain cortex. EUROPEAN JOURNAL OF PHARMACOLOGY, 269(1), 17-24.
Tipologia: | Articolo su rivista |
Citazione: | Roscetti, G., Ambrosio, C., Trabucchi, M., Massotti, M., & Barbaccia, M.L. (1994). Modulatory mechanisms of cyclic AMP-stimulated steroid content in rat brain cortex. EUROPEAN JOURNAL OF PHARMACOLOGY, 269(1), 17-24. |
IF: | Con Impact Factor ISI |
Lingua: | English |
Settore Scientifico Disciplinare: | Settore BIO/14 |
Revisione (peer review): | Sì, ma tipo non specificato |
Tipo: | Articolo |
Rilevanza: | Rilevanza internazionale |
Stato di pubblicazione: | Pubblicato |
Data di pubblicazione: | 15-set-1994 |
Titolo: | Modulatory mechanisms of cyclic AMP-stimulated steroid content in rat brain cortex |
Autori: | |
Autori: | Roscetti, G; Ambrosio, C; Trabucchi, M; Massotti, M; Barbaccia, ML |
Appare nelle tipologie: | 01 - Articolo su rivista |