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Role of the cAMP signaling pathway in the regulation of gonadotropin-releasing hormone secretion in GT1 cells.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Vitalis, Elizabeth A. Costantin, James L. Tsai, Patricia S. Sakakibara, Hideya Sreenivasan Paruthiyil Iiri, Taroh Martini, Jvana Taga, Michiyoshi Choi, Anna L. Charles, Andrew Weiner, Richard I. |
| Copyright Year | 2000 |
| Abstract | We studied the signaling pathways coupling gonadotropin-releasing hormone (GnRH) secretion to elevations in cAMP levels in the GT1 GnRH-secreting neuronal cell line. We hypothesized that increased cAMP could be acting directly by means of cyclic nucleotide-gated (CNG) cation channels or indirectly by means of activation of cAMP-dependent protein kinase (PKA). We showed that GT1 cells express the three CNG subunits present in olfactory neurons (CNG2, -4.3, and -5) and exhibit functional cAMP-gated cation channels. Activation of PKA does not appear to be necessary for the stimulation of GnRH release by increased levels of cAMP. In fact, pharmacological inhibition of PKA activity caused an increase in the basal secretion of GnRH. Consistent with this observation activation PKA inhibited adenylyl cyclase activity, presumably by inhibiting adenylyl cyclase V expressed in the cells. Therefore, the stimulation of GnRH release by elevations in cAMP appears to be the result of depolarization of the neurons initiated by increased cation conductance by cAMP-gated cation channels. Activation of PKA may constitute a negative-feedback mechanisms for lowering cAMP levels. We hypothesize that these mechanisms could result in oscillations in cAMP levels, providing a biochemical basis for timing the pulsatile release of GnRH. |
| Starting Page | 15 pp. |
| Ending Page | 15 pp. |
| Page Count | 1 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.pnas.org/content/97/4/1861.full.pdf |
| PubMed reference number | 10677547v1 |
| Volume Number | 97 |
| Issue Number | 4 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | 8-chloro-cyclic adenosine monophosphate Cations Cell secretion Gonadorelin Inhibition Nucleotides, Cyclic Pharmacology Protein Kinases Signal Transduction Pathways Wnt signaling pathway involved in midbrain dopaminergic neuron differentiation adenylate cyclase activity negative regulation of cyclic nucleotide-gated ion channel activity |
| Content Type | Text |
| Resource Type | Article |
