Differential mechanisms for PACAP and GnRH cAMP induction contribute to cross-talk between both hormones in the gonadotrope LbetaT2 cell line.
The effects and respective influence of pituitary adenylate cyclase-activating polypeptide (PACAP) and gonadotropin-releasing hormone (GnRH) on cyclic AMP (cAMP) production in pituitary gonadotropes were analyzed using the LbetaT2 cell line. Both hormones induced cAMP with, however, different intensity and time course. In addition, the GnRH effect was markedly reduced by PKC inhibitors. Despite its positive coupling to cAMP pathway, GnRH counteracted PACAP induction of cAMP and this effect was mimicked by the PKC activator phorbol 12-myristate 13-acetate (PMA). The data reveal major differences in the mechanisms by which PACAP and GnRH activate cAMP/PKA pathway in LbetaT2 cells and suggest that PKC activation serves GnRH not only to increase cAMP but also to counteract the PACAP stimulation of this signaling pathway.
Larivière
Sigolène
S
UMR CNRS 7079, Université P. & M. Curie-Paris 6, Case 256, 4 Place Jussieu, 75252 Paris cedex 05, France.
Garrel
Ghislaine
G
Robin
Marie-Thérèse
MT
Counis
Raymond
R
Cohen-Tannoudji
Joëlle
J
D000818:Animals; D002460:Cell Line; D000242:Cyclic AMP / Q000096:biosynthesis*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D006107:Granulosa Cells / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology*
D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D007987:Gonadotropin-Releasing Hormone; D000242:Cyclic AMP