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17-β Oestradiol Pretreatment of Mouse Striatal Neurons in Culture Enhances the Responses of Adenylate Cyclase Sensitive to Biogenic Amines


Dr M. Maus, as above.


Embryonic striatal neurons from the mouse grown in primary culture (6 day old culture) were used in order to investigate the effects of 17-β oestradiol (17-β E2) on biogenic amine-sensitive adenylate cyclases. Pretreatment (28 h) of intact cells with 17-β E2 (10−9 M) enhanced cyclic AMP production induced by either dopamine, isoproterenol, serotonin, or 2-chloro-adenosine (maximal effective concentrations). These effects of 17-β E2 on biogenic amine-sensitive adenylate cyclases occurred after several hours (8 h at least) and were seen in most cases with a concentration as low as 10−11 M (EC50: 10−10 M). They were additive with those induced by phenol red (5.6 μg/l) and chemically specific since 17α-oestradiol, 2(OH) 17-β E2, progesterone, and dexamethasone were without effect. In addition, they were not seen in cells which had been pretreated (30 h) with cycloheximide or α-amanitin, suggesting an involvement of de novo protein synthesis. Since 17-β E2 did not influence cyclic AMP production induced by either forskolin or manganese ions, the stimulatory effects of 17-β E2 pretreatment on biogenic amine-sensitive adenylate cyclases were not linked to an increase in the amount of enzyme catalytic units. 17-β E2 pretreatment enhanced twofold the number of β-adrenergic receptors (as estimated by the specific binding of (125l)iodocyanopindolol) but did not, in contrast, affect either the number or the affinity of dopaminergic receptors (as estimated by (125l)SCH 23982 binding). Therefore, the enhancing effects of 17-β E2 pretreatment on biogenic amine-sensitive adenylate cyclases could be related either to an increased number of coupled receptors or to modifications of the adenylate cyclase transducing system (occurring probably at the G-protein level) or to a combination of the two.

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