Luckman S M
Laboratory of Neuroendocrinology, Babraham Institute, Cambridge, UK.
Adv Exp Med Biol. 1995;395:37-48.
The activation of the magnocellular oxytocin system by different physiological stimuli will require specific genomic responses that may or may not reflect the electrical and short-term secretory activity of the neurones. One of the main determinants of synthetic activity is the rate of transcription and this can be altered acutely by the action of inducible transcription factors (iTFs). Having shown that the expression of two iTFs, the protein products of the c-fos and c-jun genes, does not correlate directly to the electrical activity of magnocellular neurones (Luckman et al., 1994) the expression of leucine zipper iTF mRNAs was measured following different stimuli using combined radioactive and non-radioactive in situ hybridization. Stimuli that are dependent on brainstem afferents such as parturition and systemic injection of cholecystokinin caused co-induction of c-fos and c-jun in oxytocin neurones. Mild osmotic stimulation, a stimulus dependent on forebrain afferents, induced c-fos, fos B and jun B, but inhibited c-jun. Similar patterns of leucine zipper iTF expression have been noted in cultured cells following activation of protein kinases C and A, respectively. Input from the brainstem appears to be mediated, at least in part, by noradrenaline acting on alpha(1)-adrenoceptors. While the forebrain inputs are not well characterised they do appear to include a glutaminergic component that may activate a variety of receptors. Interestingly, another member of the leucine zipper family known to be induced by protein kinase A, inducible cAMP early repressor (ICER), that was previously thought to be restricted to the pineal gland, was expressed in magnocellular neurones following osmotic stimulation but not parturition. Furthermore, the differential expression of iTFs is not limited to this family. Osmotic stimulation influences c-fos, but it also causes the expression of NGFI-A and NGFI-B, members of the zinc finger family of iTFs. By contrast, an acute suckling stimulus is able to induce c-fos and NGFI-A, but not nGFI-B.
不同生理刺激对大细胞催产素系统的激活需要特定的基因组反应，这些反应可能反映也可能不反映神经元的电活动和短期分泌活动。合成活动的主要决定因素之一是转录速率，而这可通过诱导型转录因子（iTFs）的作用而急性改变。已有研究表明，两种iTFs（即c-fos和c-jun基因的蛋白质产物）的表达与大细胞神经元的电活动并无直接关联（Luckman等人，1994年），因此，利用放射性和非放射性原位杂交相结合的方法，对不同刺激后亮氨酸拉链iTF mRNA的表达进行了检测。依赖脑干传入神经的刺激，如分娩和全身注射胆囊收缩素，可导致催产素神经元中c-fos和c-jun的共同诱导。轻度渗透刺激，一种依赖前脑传入神经的刺激，可诱导c-fos、fos B和jun B，但抑制c-jun。分别激活蛋白激酶C和A后，在培养细胞中也观察到了类似的亮氨酸拉链iTF表达模式。脑干的输入似乎至少部分是由去甲肾上腺素作用于α(1)-肾上腺素能受体介导的。虽然前脑输入的特征尚不明确，但它们似乎确实包括一个可能激活多种受体的谷氨酰胺能成分。有趣的是，亮氨酸拉链家族的另一个成员，即可诱导型cAMP早期阻遏物（ICER），此前被认为仅限于松果体，在渗透刺激后而非分娩后在大细胞神经元中表达。此外，iTFs的差异表达并不局限于这个家族。渗透刺激会影响c-fos，但也会导致锌指家族iTFs的成员NGFI-A和NGFI-B的表达。相比之下，急性哺乳刺激能够诱导c-fos和NGFI-A，但不能诱导nGFI-B。
