Smith R, Chan E C, Bowman M E, Harewood W J, Phippard A F
Maternal Health Research Center, John Hunter Hospital, New Lambton Heights, New South Wales, Australia.
J Clin Endocrinol Metab. 1993 Apr;76(4):1063-8. doi: 10.1210/jcem.76.4.8473382.
During human pregnancy, plasma CRH immunoreactivity (CRH-IR) rises progressively, peaking during labor and falling after delivery. Among animal species, only higher primates have elevated CRH-IR during pregnancy. This study examines whether changes in plasma CRH-IR in the baboon (Papio hamadryas) are similar to those in the human. CRH-IR was determined by RIA in 16 baboons at different stages of gestation (44 samples) and in 3 males. Assays were performed on Vycor extracts of plasma and CRH-IR diluted in parallel to synthetic human (h) CRH-41 standard. Reverse phase high pressure liquid chromatography and size-exclusion chromatography with Sephadex G-50 showed that baboon CRH-IR eluted in a position similar to that of hCRH-41. Regression analysis revealed a cubic association between plasma CRH-IR and gestational age, with peak concentrations occurring at 60 days gestation (term = 182 days). Although greatly elevated concentrations persisted throughout pregnancy, concentrations in the first half (1-91 days) were significantly higher (mean +/- SEM, 1.9 +/- 0.3 nM/L; n = 27) than in the second half (92-182 days; 1.0 +/- 0.2 nM/L; n = 11; P < 0.003 by t test). CRH-IR fell to low levels by day 1 postpartum. The concentration of total cortisol in nonpregnant animals was 1370.9 +/- 134.9 nM/L (n = 5), which was similar to pregnancy levels (1346.3 +/- 356.1 nM/L; n = 28); there was no gestational age-related pattern evident. Plasma corticosteroid-binding globulin was estimated by RIA, and plasma free cortisol was calculated to be 73 +/- 14 nM/L in pregnant animals and showed no gestational age-related changes. The mean progesterone concentration in the pregnant baboon was 12.5 +/- 2.2 nM/L (7-169 days; n = 27). There was no significant change in progesterone levels during the period of gestation studied; however, they were higher than nonpregnant levels. Baboon and human plasma (0.1 mL each) were incubated with [125I]Tyr-hCRH in Tris-HCl buffer (pH 7.5) and chromatographed with Sephadex G-75, using the same buffer. The radioactivity of fractions was determined, and no CRH-binding protein was identified in baboon plasma. This study indicates that gestational changes in CRH-IR in the baboon are different from those observed in humans. There is a dissociation between maternal plasma CRH and cortisol. The apparent lack of bioactivity of baboon plasma CRH is not due to a circulating binding protein, which is absent in this species.
在人类孕期，血浆促肾上腺皮质激素释放激素免疫反应性（CRH-IR）逐渐升高，在分娩时达到峰值，产后下降。在动物物种中，只有高等灵长类动物在孕期CRH-IR会升高。本研究探讨狒狒（阿拉伯狒狒）血浆CRH-IR的变化是否与人类相似。通过放射免疫分析法（RIA）测定了16只处于不同妊娠阶段的狒狒（44份样本）和3只雄性狒狒的CRH-IR。检测在血浆的Vycor提取物上进行，CRH-IR与合成人（h）CRH-41标准品平行稀释。反相高压液相色谱和用Sephadex G-50进行的尺寸排阻色谱显示，狒狒CRH-IR的洗脱位置与hCRH-41相似。回归分析显示血浆CRH-IR与妊娠年龄呈三次方关联，峰值浓度出现在妊娠60天时（足月为182天）。尽管整个孕期浓度持续大幅升高，但前半期（1 - 91天）的浓度（均值±标准误，1.9±0.3 nM/L；n = 27）显著高于后半期（92 - 182天；1.0±0.2 nM/L；n = 11；经t检验P < 0.003）。产后第1天CRH-IR降至低水平。未怀孕动物的总皮质醇浓度为1370.9±134.9 nM/L（n = 5），与孕期水平（1346.3±356.1 nM/L；n = 28）相似；未观察到与妊娠年龄相关的模式。通过RIA估算血浆皮质类固醇结合球蛋白，计算得出怀孕动物的血浆游离皮质醇为73±14 nM/L，未显示出与妊娠年龄相关的变化。怀孕狒狒的平均孕酮浓度为12.5±2.2 nM/L（7 - 169天；n = 27）。在所研究的妊娠期内孕酮水平无显著变化；然而，它们高于未怀孕时的水平。将狒狒和人类血浆（各0.1 mL）与[125I]酪氨酸-hCRH在Tris-HCl缓冲液（pH 7.5）中孵育，并用相同缓冲液在Sephadex G-75上进行色谱分析。测定各组分的放射性，在狒狒血浆中未鉴定出CRH结合蛋白。本研究表明，狒狒CRH-IR的妊娠变化与人类观察到的不同。母体血浆CRH与皮质醇之间存在分离。狒狒血浆CRH明显缺乏生物活性并非由于循环结合蛋白，该物种不存在这种蛋白。
