Protein kinase C cross-talk with gonadotrope progesterone receptor is involved in GnRH-induced LH secretion

RESUMEN

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ABSTRACT

In the absence of progesterone (P), the anti-P at the receptor RU486 reduces basaland GnRH-stimulated LH secretion both in vivo and in vitro, demonstrating theexistence of a ligand-independent activation of progesterone receptor (LIAPR). Theaim of the present study was to determine which component of the intracellular LHsecretory pathway activated by GnRH is responsible for LIAPR. To do this, anteriorpituitary dispersed cells from female rats in proestrus, cultured in the presence of17â-estradiol, were incubated with activators or inhibitors of PKC, cAMP-PKA signallingpathways or intracellular calcium (Ca2+) traffic, in the presence or absence ofRU486. Results showed that RU486 reduced both GnRH- and the PKC activatorPMA-induced LH secretion. In GnRH-stimulated cells incubated with the PKCinhibitor BIS-I or treated with PMA “overnight”, RU486 had no effect on reducedLH secretion, nor on stimulated LH secretion elicited by the Ca2+ ionophore ionomycin.Moreover, when GnRH- or PMA-treated cells were co-incubated with 1 µMof the L-type Ca2+ channel blocker nifedipine or the intracellular Ca2+ chelatorBAPTA-AM, RU486 potentiated the expected inhibition of these drugs on LHsecretion. Activation (forskolin, 8-Br-cAMP) or inhibition (MDL-12,330A) of thecAMP-PKA signalling cascade affected neither the GnRH- and PMA-inducedincrease of LH secretion nor the reduction of LH secretion due to RU486. Takentogether, the data point to the existence of a Ca2+-independent PKC-PR cross-talkmechanism as part of the intracellular signalling of GnRH-stimulated LH secretion