Cesnjaj M, Krsmanovic L Z, Catt K J, Stojilkovic S S
Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
Endocrinology. 1993 Dec;133(6):3042-5. doi: 10.1210/endo.133.6.8243334.
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.
促性腺激素释放激素（GnRH）神经元（GT1-7）细胞中GnRH受体的激活会导致c-fos表达显著且短暂增加，在30分钟时达到峰值反应。GnRH和去甘氨酸10-[D-丙氨酸6]GnRH N-乙酰胺诱导浓度依赖性的c-fos反应，其半数有效浓度（EC50）分别约为0.1 nM和约1 nM。佛波酯12-肉豆蔻酸酯-13-乙酸酯（PMA）可模拟GnRH的作用，但钾离子（K⁺）诱导的去极化和Bay K 8644对钙离子（Ca²⁺）内流的刺激效果要差得多。在蛋白激酶C缺失的细胞中，GnRH诱导的c-fos反应降低至钙离子内流增加所引发的水平，且PMA的作用被消除。因此，GnRH诱导GT1细胞中c-fos表达似乎主要由蛋白激酶C介导，其次由钙离子介导。这些发现表明，通过激活其神经分泌产物的受体，可在肽能神经元中诱导c-fos表达。在促性腺激素发情前期激增期间，GnRH下丘脑神经元中c-fos的表达同样有可能受到GnRH对其神经元受体的正反馈作用刺激。
