AUTOCRINE INDUCTION OF C-FOS EXPRESSION IN GT1 NEURONAL CELLS BY GONADOTROPIN-RELEASING-HORMONE

Activation of GnRH receptors in GnRH neuronal (GT1-7) cells causes marked and transient increases in c-fos expression, with peak response at 30 min. GnRH and des-Gly10-[D-Ala6]GnRH N-ethylamide induced concentration-dependent c-fos responses with EC50s of approximately 0.1 and approximately 1 nM, respectively. GnRH action was mimicked by phorbol 12-myristate-13-acetate (PMA), but stimulation of Ca2+ entry by K+-induced depolarization and Bay K 8644 was much less effective. In protein kinase C-depleted cells, the c-fos response to GnRH was reduced to that elicited by increased Ca2+ entry, and the effect of PMA was abolished. Thus, GnRH-induced c-fos expression in GT1 cells appears to be mediated predominantly by protein kinase C, and to a lesser extent by Ca2+. These findings demonstrate that c-fos expression can be induced in a peptidergic neuron by activation of receptors for its neurosecretory product. It is possible that the expression of c-fos in GnRH hypothalamic neurons during the proestrous surge of gonadotropins could likewise be stimulated by a positive feedback action of GnRH on its neuronal receptors.