Goland R S, Wardlaw S L, Fortman J D, Stark R I
Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032.
Endocrinology. 1992 Oct;131(4):1782-6. doi: 10.1210/endo.131.4.1396323.
We have studied the secretion of placental CRF during pregnancy in the baboon, an animal model with many similarities to human pregnancy. Plasma CRF was measured in two groups of animals. In group 1, studies were performed in six anesthetized animals beginning 8 days postconception. In group 2, studies were performed in five unanesthetized chronically catheterized maternal and five fetal animals in the latter third of pregnancy. In the first study beginning early in pregnancy, CRF was undetectable in all animals on days 8 and 15 postconception. Plasma CRF became detectable in two animals on day 24 and in the remaining four on day 30. Plasma CRF rose significantly to a mean of 810 +/- 160 pg/ml at 37 days gestation (F = 4.20; P < 0.001). Mean maternal plasma CRF was 2452 +/- 1120 pg/ml on day 44 and remained elevated, with a great deal of variability between subjects, until the end of the study period (128 days of gestation). Samples in this group were obtained after ketamine sedation. The effect of ketamine on CRF was studied in three chronically catheterized animals. Samples were obtained before and 2, 4, 6, and 24 h after ketamine administration (40 mg, iv). The baseline CRF concentration was 1168 +/- 131 pg/ml and did not change significantly over the time period studied. In the second study in the chronically catheterized animals, maternal plasma CRF was 1990 +/- 680 pg/ml at 131-140 days gestation and remained elevated until near term at 170 days (term = 175-180 days). Within 24 h after birth, plasma CRF became undetectable (< 60 pg/ml). CRF was also measured in chronically catheterized fetal baboons. The mean CRF concentration was 614 +/- 224 pg/ml at 131-140 days and remained in this range until the end of the period studied (151-160 days gestation). To characterize the CRF immunoactivity in maternal baboon plasma, Sephadex chromatography was performed on an 8.4-ml plasma sample obtained at 160 days gestation. The majority of the CRF immunoactivity eluted in the same position as synthetic human CRF. We conclude that high levels of placental CRF are present in the systemic circulation of the maternal and fetal baboon during pregnancy. In contrast to human pregnancy, which is characterized by an exponential rise in maternal CRF concentrations in the final weeks before delivery, an exponential rise in maternal baboon CRF concentrations occurs early in pregnancy.
我们在狒狒身上研究了孕期胎盘促肾上腺皮质激素释放因子(CRF)的分泌情况,狒狒是一种与人类孕期有许多相似之处的动物模型。对两组动物的血浆CRF进行了测量。在第1组中,对6只麻醉动物从受孕后8天开始进行研究。在第2组中,对5只未麻醉的长期插管的孕母动物和5只孕晚期胎儿动物进行了研究。在孕期早期开始的第一项研究中,受孕后第8天和第15天,所有动物体内均未检测到CRF。在第24天,两只动物的血浆CRF可检测到,其余4只在第30天可检测到。妊娠37天时,血浆CRF显著升高至平均810±160 pg/ml(F = 4.20;P < 0.001)。孕母血浆CRF在第44天时为2452±1120 pg/ml,并一直保持升高,个体间差异很大,直至研究期末(妊娠128天)。该组样本在氯胺酮镇静后采集。在3只长期插管的动物中研究了氯胺酮对CRF的影响。在静脉注射氯胺酮(40 mg)前以及注射后2、4、6和24小时采集样本。基线CRF浓度为1168±131 pg/ml,在所研究的时间段内无显著变化。在长期插管动物的第二项研究中,孕母血浆CRF在妊娠131 - 140天时为1990±680 pg/ml,并一直保持升高直至接近足月时的170天(足月为175 - 180天)。出生后24小时内,血浆CRF变得无法检测到(< 60 pg/ml)。还对长期插管的狒狒胎儿进行了CRF测量。在131 - 140天时,平均CRF浓度为614±224 pg/ml,并在研究期末(妊娠151 - 160天)一直保持在该范围内。为了鉴定孕母狒狒血浆中的CRF免疫活性,对妊娠160天时获得的8.4 ml血浆样本进行了葡聚糖凝胶色谱分析。大多数CRF免疫活性与合成人CRF在相同位置洗脱。我们得出结论,孕期母狒狒和胎儿狒狒的体循环中存在高水平的胎盘CRF。与人类孕期不同,人类孕期的特点是分娩前最后几周孕母CRF浓度呈指数上升,而母狒狒CRF浓度在孕期早期呈指数上升。