STIMULATORY EFFECTS OF 5HT(1A) RECEPTOR AGONISTS ON LUTEINIZING-HORMONE-RELEASING HORMONE-RELEASE FROM CULTURED FETAL-RAT HYPOTHALAMIC CELLS - INTERACTIONS WITH PROGESTERONE

Previous works have suggested an interactive stimulatory effect of pro gesterone CP) and serotonin (5-HT) on luteinizing hormone release. The purpose of the present study was to determine whether 5-HT via 5-HT1A receptors interacts with P in the process of luteinizing hormone-rele asing hormone (LHRH) release. Using fetal hypothalamic neurons in prim ary cell cultures the first goal of this study was to determine the ef fects of 5-HT1A receptor agonists on LHRH secretion. 8-Hydroxy-2(di-n- propylamino) tetralin (8-OH-DPAT) or ipsapirone (10(-5) M) significant ly stimulated LHRH release. Pharmacological studies have allowed to ru le out the possible involvement of alpha(2)- or beta-adrenoreceptors, or 5-HT uptake sites, in the stimulatory effect of 8-OH-DPAT on LHRH r elease, thus demonstrating the specific involvement of 5-HT1A receptor s in the stimulation of LHRH release. The second goal was to test the ability of P to stimulate LHRH release from fetal hypothalamic neurons . P (10(-6) M) applied for 30 or 120 min significantly stimulated LHRH secretion. The maintenance of the stimulation of LHRH release by P af ter a cycloheximide treatment or by an impermeable analog of P, P-3-BS A, has suggested a nongenomic effect of P on LHRH release. The effects of a pretreatment of cells by P on 8-OH-DPAT-induced LHRH release wer e tested. While 10(-7)M P alone did not stimulate LHRH release, this c oncentration of steroid potentiated the LHRH response to 10(-5) M 8-OH -DPAT. These findings led to the conclusion that P acting at the level of the plasma membrane potentiates the stimulatory effect of 5-HT1A r eceptor agonists on LHRH release.