Varshney C, Rivera M, Gintzler A R
Department of Biochemistry, State University of New York Health Science Center at Brooklyn, N.Y., USA.
Neuroendocrinology. 1999 Oct;70(4):268-79. doi: 10.1159/000054486.
Gestation as well as its hormonal simulation (HSP) is characterized by an enhanced spinal dynorphin/kappa-opioid antinociception. This antinociception is accompanied by decreased content of dynorphin precursor intermediates and increased content of mature dynorphin peptides (1-17 and 1-8) in the lumbar spinal region. This suggests that augmented processing of spinal dynorphin precursor intermediates is an adaptive mechanism used by dynorphin neurons to meet increased synthetic demands necessitated by increased dynorphin neurotransmission. Prohormone convertase (PC) 1 and 2 represent major secretory granule proteolytic processing activities capable of converting neuroendocrine and neurotransmitter peptide (dynorphin) precursor intermediates to their mature, biologically active products. Accordingly, the current investigation was undertaken to assess their potential relevance to peptidergic (dynorphin) neuronal functional plasticity in vivo. In order to evaluate a molecular biological parameter of PC2 synthesis, a solution hybridization assay was developed with which to quantify changes in the spinal lumbar content of its mRNA. This study demonstrates that during gestation and HSP, lumbar PC2 protein content, but not that of PC1, is augmented. The increase in lumbar PC2 during HSP indicates that the pregnancy blood concentration profile of 17beta-estradiol and progesterone is a predominant facet of the pregnant condition responsible for its modulation during this condition. In contrast to the elevated content of lumbar PC2 protein, levels of PC2 mRNA in the lumbar cord of pregnant or HSP rats were essentially unchanged. This indicates that increased transcriptional activity is not, necessarily, a prerequisite for increased PC2 protein content to be manifest. These observations suggest positive modulation of PC2 to be a critical component of the mechanism(s) by which spinal dynorphin neurons adapt to the demand-induced increased production of mature dynorphin peptides.
妊娠及其激素模拟（HSP）的特征是脊髓强啡肽/κ-阿片类抗伤害感受增强。这种抗伤害感受伴随着腰段脊髓区域强啡肽前体中间体含量的降低和成熟强啡肽肽（1-17和1-8）含量的增加。这表明脊髓强啡肽前体中间体加工的增强是强啡肽神经元用于满足强啡肽神经传递增加所必需的合成需求增加的一种适应性机制。激素原转化酶（PC）1和2代表主要的分泌颗粒蛋白水解加工活性，能够将神经内分泌和神经递质肽（强啡肽）前体中间体转化为其成熟的、具有生物活性的产物。因此，本研究旨在评估它们与体内肽能（强啡肽）神经元功能可塑性的潜在相关性。为了评估PC2合成的分子生物学参数，开发了一种溶液杂交测定法，用于量化其mRNA在腰段脊髓中的含量变化。本研究表明，在妊娠和HSP期间，腰段PC2蛋白含量增加，而PC1蛋白含量未增加。HSP期间腰段PC2的增加表明，17β-雌二醇和孕酮的妊娠血浓度曲线是妊娠状态的一个主要方面，负责在此状态下对其进行调节。与腰段PC2蛋白含量升高相反，妊娠或HSP大鼠腰段脊髓中PC2 mRNA水平基本未变。这表明转录活性增加不一定是PC2蛋白含量增加得以显现的先决条件。这些观察结果表明，PC2的正向调节是脊髓强啡肽神经元适应需求诱导的成熟强啡肽肽产量增加的机制的关键组成部分。
