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大鼠中肽-23/胰腺炎相关蛋白和胰石蛋白/reg基因表达的年龄相关变化及生长激素释放激素的调节作用

Age-related changes in peptide-23/pancreatitis-associated protein and pancreatic stone protein/reg gene expression in the rat and regulation by growth hormone-releasing hormone.

作者信息

Chakraborty C, Katsumata N, Myal Y, Schroedter I C, Brazeau P, Murphy L J, Shiu R P, Friesen H G

机构信息

Department of Physiology, University of Manitoba, Winnipeg, Canada.

出版信息

Endocrinology. 1995 May;136(5):1843-9. doi: 10.1210/endo.136.5.7720628.

DOI:10.1210/endo.136.5.7720628
PMID:7720628
Abstract

Peptide-23 is a 16-kilodalton protein secreted by rat pituitary cells that was first identified because it was regulated by GRF and somatostatin in a similar fashion to GH. Cloning of peptide-23 complementary DNA revealed that it is identical to pancreatitis-associated protein (PAP) and a member of the c-lectin gene family. We examined the expression of peptide-23/PAP and a structurally related protein, pancreatic stone protein (PSP/reg), in the rat gastrointestinal tract. Here we report age-related changes in the expression and GRF regulation of peptide-23. Both peptide-23/PAP messenger RNA (mRNA) and PSP/reg mRNA were virtually undetectable in the small intestine of newborn and 1- and 2-week-old rats. A dramatic increase in the expression of both genes was seen at the time of weaning in the third week postpartum. The abundance of both of these mRNA decreases after 3 and 6 months of age. Peptide-23/PAP mRNA is most abundant in the ileum, whereas PSP/reg is maximally expressed in the pancreas and duodenum. Human GRF analog pellets were implanted sc into adult male rats for 2 weeks to study the chronic effects of GRF on the expression of these genes. Both peptide-23/PAP and PSP/reg mRNA levels in duodenum and jejunum were increased in these rats compared with levels in control rats. However, no increase in peptide-23/PAP mRNA in response to GRF treatment was seen in the ileum, where the level of expression of this gene is very high, and GRF had no effect on peptide-23/PSP expression in the heart, pituitary, or hypothalamus, where expression is normally undetectable. In situ hybridization was used to localize peptide-23/PSP in the small intestine and pancreas of GRF-treated rats. An increase in peptide-23/PAP mRNA was restricted to acinar cells close to islets, whereas little expression was seen in acinar cells distant from islets, suggesting that either peptide-23/PAP may have some paracrine action on the islets, or alternatively, an islet-derived factor may function as a paracrine modulator of peptide-23/PAP expression. These data demonstrate that GRF modulates peptide-23/PAP expression in the gastrointestinal tract in a similar fashion to that previously reported for pituitary cells in primary culture.

摘要

肽 - 23是一种由大鼠垂体细胞分泌的16千道尔顿蛋白质,它最初被鉴定出来是因为它受生长激素释放因子(GRF)和生长抑素的调节,其方式与生长激素(GH)相似。肽 - 23互补DNA的克隆显示它与胰腺炎相关蛋白(PAP)相同,是c - 凝集素基因家族的成员。我们检测了肽 - 23/PAP和一种结构相关蛋白——胰石蛋白(PSP/reg)在大鼠胃肠道中的表达。在此我们报告肽 - 23表达及GRF调节的年龄相关变化。在新生大鼠以及1周龄和2周龄大鼠的小肠中,几乎检测不到肽 - 23/PAP信使核糖核酸(mRNA)和PSP/reg mRNA。在产后第三周断奶时,这两种基因的表达显著增加。在3个月和6个月龄后,这两种mRNA的丰度下降。肽 - 23/PAP mRNA在回肠中最丰富,而PSP/reg在胰腺和十二指肠中表达最高。将人GRF类似物微丸皮下植入成年雄性大鼠2周,以研究GRF对这些基因表达的慢性影响。与对照大鼠相比,这些大鼠十二指肠和空肠中的肽 - 23/PAP和PSP/reg mRNA水平均升高。然而,在回肠中,该基因表达水平非常高,GRF处理后肽 - 23/PAP mRNA未见增加,并且GRF对心脏、垂体或下丘脑(这些部位通常检测不到该基因表达)中的肽 - 23/PSP表达没有影响。原位杂交用于在GRF处理大鼠的小肠和胰腺中定位肽 - 23/PSP。肽 - 23/PAP mRNA的增加仅限于靠近胰岛的腺泡细胞,而在远离胰岛的腺泡细胞中几乎未见表达,这表明要么肽 - 23/PAP可能对胰岛有某种旁分泌作用,要么胰岛衍生因子可能作为肽 - 23/PAP表达的旁分泌调节因子。这些数据表明,GRF以与先前报道的原代培养垂体细胞类似的方式调节胃肠道中肽 - 23/PAP的表达。

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