The catecholaminergic stimulation of gonadotropin-releasing hormone release by GT1-1 cells does not involve phosphoinositide hydrolysis.
Gonadotropin-releasing hormone (GnRH) secretion is modulated by a large number of neuromediators, among which catecholamines play a central role. Previous results have shown that both dopamine (DA) and norepinephrine (NE) stimulate GnRH secretion in GT1 neuronal cell lines. These stimulatory effects appear to involve D1-dopaminergic and beta 1-adrenergic receptors positively coupled to adenylate cyclase. However, in spite of a similar efficacy of these catecholamines to stimulate GnRH secretion, DA is two-fold more efficacious than NE to stimulate the formation of cyclic AMP. This rises the possibility that other signaling pathways and other receptor subtypes could be involved in the catecholaminergic stimulation of GnRH release. Since the signaling pathway triggered by phosphoinositide hydrolysis is a potent stimulator of GnRH secretion and appears to mediate the releasing actions of neuromediators such as histamine and endothelin, we investigated if this signaling pathway was also involved in the catecholaminergic stimulation of GnRH release in GT1 cells. Both DA and NE stimulated inositol phosphates production in GT1-1 cells with a very low potency and long latency with respect to GnRH secretion. Inositol phosphates production was stimulated by DA and NE only at a concentration of 100 microM, i.e. two to three orders of magnitude higher than the effective concentrations to maximally stimulate GnRH secretion. The effects of both catecholamines do not appear to be secondary to the stimulation of cyclic AMP production, since treatment of GT1-1 cells with forskolin did not affect inositol phosphates production. The effects of DA and NE on inositol phosphates production were blocked by specific antagonists such as SCH-23390, spiroperidol and phentolamine. However, specific dopaminergic agonists such as SKF-38393 and bromocriptine, or adrenergic agonists such as clonidine, methoxamine and isoproterenol were not capable of stimulating inositol phosphates production. Thus, due to the low potency and apparent non-specificity of these effects, we conclude that inositol phosphates production is not involved in the catecholaminergic stimulation of GnRH release.
Segovia
C T
CT
Neurobiology Center, National University of Mexico, Mexico City.
Salgado
Z O
ZO
Clapp
C
C
Martínez de la Escalera
G
G
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D002460:Cell Line; D000242:Cyclic AMP / Q000096:biosynthesis; D004298:Dopamine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007295:Inositol Phosphates / Q000096:biosynthesis; D009638:Norepinephrine / Q000494:pharmacology*; D015290:Second Messenger Systems
D000316:Adrenergic alpha-Agonists; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D007295:Inositol Phosphates; D007987:Gonadotropin-Releasing Hormone; D000242:Cyclic AMP; D004298:Dopamine; D009638:Norepinephrine