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.
Cesnjaj
M
M
Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
Krsmanovic
L Z
LZ
Catt
K J
KJ
Stojilkovic
S S
SS
D002461:Cell Line, Transformed; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D007987:Gonadotropin-Releasing Hormone; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate