Regulation of gonadotropin-releasing hormone release by cyclic AMP signalling pathways.
The frequency and amplitude of gonadotropin-releasing hormone (GnRH) pulses are tightly regulated for the maintenance of reproductive cycles. Pulsatile GnRH release was shown to be an intrinsic property of murine GT1 GnRH neurons, and primate placodal GnRH neurons. GT1 neurons show spontaneous action potentials that are associated with Ca2+ oscillations and hormone secretion. Increased cyclic AMP (cAMP) levels in GT1 neurons appear to stimulate GnRH release by activation of cAMP-gated cation (CNG) channels. Activation of the CNG channels correlated with increased neuron excitability and Ca2+ oscillations. Activation of protein kinase A is not necessary for cAMP-induced stimulation of GnRH secretion, but appears to activate negative feedback pathways. Potential negative feedback pathways may decrease cAMP levels by inhibiting adenylyl cyclase V, and activating the phosphodiesterase, PDE4D3. These stimulatory and inhibitory cAMP-signalling pathways appear to regulate the excitability of the GT1 neurons, and may constitute a biological clock timing the pulsatile release of GnRH.
Weiner
R I
RI
Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco School of Medicine, 94143, USA. weinerr@obgyn.ucsf.edu
Charles
A
A
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D054815:Cyclic Nucleotide-Gated Cation Channels; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D015398:Signal Transduction
D054815:Cyclic Nucleotide-Gated Cation Channels; D007473:Ion Channels; D007987:Gonadotropin-Releasing Hormone; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D010727:Phosphoric Diester Hydrolases; D000262:Adenylyl Cyclases