Stimulatory effects of 5HT1A 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 progesterone (P) 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-releasing hormone (LHRH) release. Using fetal hypothalamic neurons in primary cell cultures the first goal of this study was to determine the effects of 5-HT1A receptor agonists on LHRH secretion. 8-Hydroxy-2 (di-n-propylamino) tetralin (8-OH-DPAT) or ipsapirone (10(-5) M) significantly stimulated LHRH release. Pharmacological studies have allowed to rule 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 release, thus demonstrating the specific involvement of 5-HT1A receptors 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 after a cycloheximide treatment or by an impermeable analog of P, P-3-BSA, 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 were tested. While 10(-7) M P alone did not stimulate LHRH release, this concentration 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 receptor agonists on LHRH release.
Héry
M
M
Laboratoire de Neuroendocrinologie Expérimentale, INSERM U-297, Institut Fédératif, Jean Roche, Faculté de Médecine Nord, Marseille, France.
Becquet
D
D
François-Bellan
A M
AM
Deprez
P
P
Fache
M P
MP
Héry
F
F
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D004347:Drug Interactions; D005069:Evaluation Studies as Topic; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012636:Secretory Rate / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013268:Stimulation, Chemical
D017366:Serotonin Receptor Agonists; D012701:Serotonin; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin