CENTRAL REGULATION OF ADRENOCORTICOTROPIN SECRETION

促肾上腺皮质激素释放因子（CRF-4l）产生的细胞核 下丘脑室旁小细胞核（pPVN）在 在调节腺垂体促肾上腺皮质激素（ACTH）中的作用 分泌，前阿黑皮素（POMC）基因表达，因此，在 调节肾上腺皮质分泌。 的分泌活动 CRF阳性神经元受体液因子（糖皮质激素， 葡萄糖等）和许多传入纤维传递信息， 内感受和外感受刺激。 CRF-41神经元接受重 来自髓质细胞群的神经支配，这些细胞群本身接受 各种内脏和躯体感觉输入。 因此它们 很好的候选者， 下丘脑-垂体-肾上腺（HPA）轴对一些 内脏（例如血容量不足、低血压）和躯体（例如疼痛）刺激。 来自延髓区的传出神经是输入神经的主要来源 含有去甲肾上腺素（NE）、肾上腺素（EPI）、神经肽Y（NPY）， 和具有激活素样免疫反应性的肽（I β A-LI）， 富含CRF的pPVN。 这些假定的递质通常促进CRF-41 分泌，虽然肾上腺素能受体亚型介导的性质， 儿茶酚胺的作用仍有争议。 最终，机制必须 以确保基因表达和分泌的协调。 在 我们将测试这个假设，无论是个人还是 组合，NE和I β A-LI（TGF-β生长因子的成员 家族）参与CRF-41分泌与基因表达的协调 表情 由于这些递质的生物化学多样性 以及它们以特定方式释放的可能性 取决于刺激特性（模态，幅度， 频率，持续时间），我们假设这些发射器 差异影响靶细胞的分泌和基因表达 通过多种细胞内途径。 神经递质释放唤起 神经元的快速和缓慢反应，从而允许立即 对刺激的反应以及长期适应性可塑性。 它 已经提出，c-fos基因的诱导，该基因编码 具有DNA结合特性的核磷蛋白， 转录调节因子，是信号级联的一个组成部分， 哪些特定的递质可以调节神经元基因的表达。 因此，我们将评估这些神经递质 激活c-fos基因，然后确定C-fos是否 活化与CRF-41分泌和/或基因表达相关。

Corticotropin releasing factor (CRF-4l)-producing perikarya in the hypothalamic parvocellular paraventricular nuclei (pPVN) play an integral role in regulation of adenohypophysial adrenocorticotropin (ACTH) secretion, pro-opiomelanocortin (POMC) gene expression and, thus, in the regulation of adrenocortical secretion. The secretory activity of CRF-positive neurons is modulated by humoral factors (glucocorticoids, glucose, etc) and by numerous afferent fibers conveying information about interoceptive and exteroceptive stimuli. CRF-41 neurons receive heavy innervation from medullary cell groups which, themselves, receive a diverse array of visceral and somatosensory inputs. Therefore they are excellent candidates for mediating activation of the hypothalamic-pituitary-adrenal (HPA) axis in response to a number of visceral (e.g. hypovolemia, hypotension) and somatic (e.g. pain) stimuli. Efferents from medullary regions are the major source of inputs containing norepinephrine (NE), epinephrine (EPI), neuropeptide Y (NPY), and a peptide with activin-like immunoreactivity (IbetaA-LI) to the CRF-rich pPVN. These putative transmitters generally facilitate CRF-41 secretion, although the nature of adrenergic receptor subtypes mediating catecholamine actions remain controversial. Ultimately, mechanisms must exist to ensure coordination of gene expression and secretion. In the present proposal, we will test the hypothesis that, individually or in combination, NE and IbetaA-LI (a member of the TGF-beta growth factor family) participate in the coordination of CRF-41 secretion and gene expression. Because of the biochemical diversity of these transmitters and the likelihood that their release occurs in a specific manner dependent upon the stimulus characteristics (modality, amplitude, frequency, duration), we hypothesize that these transmitters differentially affect secretion and gene expression in the target cells via multiple intracellular pathways. Neurotransmitter release evokes both rapid and slow responses in neurons, thus permitting an immediate response to the stimulus as well as longer-term adaptive plasticity. It has been suggested that induction of the c-fos gene, which encodes a nuclear phosphoprotein with DNA binding properties consistent that of a transcriptional regulator, is a component of the signaling cascade by which specific transmitters may modulate neuronal gene expression. Therefore, we will evaluate whether any of these neurotransmitters activate the c-fos gene and then determine whether or not C-fos activation is correlated with CRF-41 secretion and/or gene expression.