Lowry P J
Department of Biochemistry & Physiology, School of Animal and Microbial Sciences, University of Reading, Whiteknights, UK.
Ciba Found Symp. 1993;172:108-15; discussion 115-28.
CRF is unusual in that it is synthesized and released from the placenta into the circulation in humans, reaching levels in the third trimester that would normally be expected in the hypothalamic portal system during stress. This rise is even more pronounced in pregnancy-induced hypertension and preterm labour. Paradoxically, there is no associated rise of either ACTH or cortisol. This lack of biological response and the stability of the peptide in human (but not rat) plasma in vitro initiated a search for the human CRF-binding plasma protein. This CRF-BP proved to have a molecular mass in the region of 40 kDa, and has been purified to homogeneity. It has an affinity constant in the nanomolar range and when mixed with appropriate amounts of CRF completely inhibits the ACTH-releasing activity of the peptide in vitro. With the cloning of the cDNA for CRF-BP, sufficient pure material has become available for the development of a radioimmunoassay. Although CRF-BP levels in pregnant women are normal in the second trimester, they begin to fall by week 35, reaching approximately 50% of normal values by term. The net effect of this would be an accelerated increase in free, potentially biologically active CRF.
促肾上腺皮质激素释放因子（CRF）的不同寻常之处在于，在人类中它是由胎盘合成并释放到循环系统中的，在妊娠晚期其水平达到了通常在应激状态下下丘脑门脉系统中才会出现的水平。这种升高在妊娠高血压和早产中更为明显。矛盾的是，促肾上腺皮质激素（ACTH）或皮质醇并没有相应升高。这种缺乏生物学反应以及该肽在人（而非大鼠）血浆中的体外稳定性，引发了对人CRF结合血浆蛋白的研究。这种CRF结合蛋白（CRF-BP）的分子量在40 kDa左右，已被纯化至同质。它的亲和常数在纳摩尔范围内，与适量的CRF混合时，能在体外完全抑制该肽的促肾上腺皮质激素释放活性。随着CRF-BP的cDNA被克隆，已有足够的纯物质可用于开发放射免疫测定法。尽管孕妇在妊娠中期的CRF-BP水平正常，但到第35周时开始下降，足月时降至正常值的约50%。其净效应将是游离的、具有潜在生物活性的CRF加速增加。
