Davenport M L, Pucilowska J, Clemmons D R, Lundblad R, Spencer J A, Underwood L E
Department of Pediatrics, School of Medicine, University of North Carolina, Chapel Hill 27599.
Endocrinology. 1992 May;130(5):2505-12. doi: 10.1210/endo.130.5.1374007.
The abundances of insulin-like growth factor binding proteins (IGFBPs) in sera and tissue homogenates of rats at days 12, 15, and 18 of pregnancy were determined by ligand- and immunoblotting. As in serum, IGFBP-3 was abundant in day 12 uterus, placenta, and fetuses, and decreased by day 15. On day 18 of pregnancy, IGFBP-2 was predominant and IGFBP-3 was less than 25% of day 12 values in fetus and placenta, and was undetectable in uterus and decidua. In contrast, IGFBPs in the nonreproductive tissues did not change significantly. IGFBP-3 was more abundant in muscle than heart and liver, and was not detected in lung, kidney, or brain. The decrease in IGFBP-3 in serum and reproductive tissues between days 12 and 15 of pregnancy was temporally related to the appearance of IGFBP-3 protease activity. Proteolytic activity was detectable only at low levels in brain, liver, and spleen, and was undetectable in lung, heart, muscle, and kidney. The specific protease inhibitors that blocked IGFBP-3 proteolytic activities in pregnant rat serum and decidua were virtually identical and suggested inhibition of a divalent cation-dependent tryptic-like serine protease. Furthermore, exposure of bovine IGFBP-3 (in nonpregnant bovine serum) or radiolabeled recombinant human IGFBP-3 to day 18 pregnant rat serum, decidua or uterus resulted in the generation of IGFBP-3 fragments with the same apparent Mrs (29-31 K and 18-23 K). We postulate that tissue-specific degradation may be as important as synthesis in determining IGFBP-3 abundance, and that the dramatic changes in IGFBPs in reproductive and fetal tissues may cause changes in IGF availability which are necessary for rapid tissue growth and differentiation.
通过配体印迹法和免疫印迹法测定了妊娠第12、15和18天大鼠血清和组织匀浆中胰岛素样生长因子结合蛋白（IGFBPs）的丰度。与血清中情况一样，IGFBP - 3在妊娠第12天的子宫、胎盘和胎儿中含量丰富，到第15天减少。在妊娠第18天，IGFBP - 2占主导地位，胎儿和胎盘组织中IGFBP - 3含量低于第12天值的25%，在子宫和蜕膜中未检测到。相比之下，非生殖组织中的IGFBPs没有明显变化。IGFBP - 3在肌肉中的含量高于心脏和肝脏，在肺、肾或脑中未检测到。妊娠第12天和第15天之间血清和生殖组织中IGFBP - 3的减少与IGFBP - 3蛋白酶活性的出现存在时间关联。蛋白水解活性仅在脑、肝和脾中低水平可检测到，在肺、心脏、肌肉和肾中未检测到。阻断妊娠大鼠血清和蜕膜中IGFBP - 3蛋白水解活性的特异性蛋白酶抑制剂实际上是相同的，提示抑制了一种二价阳离子依赖性胰蛋白酶样丝氨酸蛋白酶。此外，将牛IGFBP - 3（来自未妊娠牛血清）或放射性标记的重组人IGFBP - 3暴露于妊娠第18天的大鼠血清、蜕膜或子宫，会产生表观分子量相同（29 - 31K和18 - 23K）的IGFBP - 3片段。我们推测，在决定IGFBP - 3丰度方面，组织特异性降解可能与合成同样重要，并且生殖和胎儿组织中IGFBPs的显著变化可能导致IGF可用性的改变，这对于组织的快速生长和分化是必要的。
