Goland R S, Wardlaw S L, MacCarter G, Warren W B, Stark R I
Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032.
J Clin Endocrinol Metab. 1991 Aug;73(2):257-61. doi: 10.1210/jcem-73-2-257.
CRH is secreted by the placenta into the maternal and fetal circulation during pregnancy in humans and non-human primates. ACTH and cortisol responses to exogenous CRH are blunted during pregnancy. In the present study we examined the pituitary-adrenal response to another corticotropin releasing factor, vasopressin. Studies were performed in chronically catheterized female baboons moving freely in their home cages; 13 studies were performed in 4 pregnant animals, and 8 studies were performed in 6 nonpregnant animals. Vasopressin was administered iv in 2 doses (0.3 and 3.0 U), and plasma samples were obtained for CRH, ACTH, and cortisol measurements. Results are expressed as the mean +/- SEM. Baseline plasma CRH was 240 +/- 20 pmol/L in the pregnant animals and unmeasurable (less than 20) in the nonpregnant animals. In the pregnant animals, ACTH concentrations rose from a baseline of 6.4 +/- 1.3 pmol/L to 10.1 +/- 0.4 after 0.3 U vasopressin and to 24.9 +/- 5.2 after 3.0 U vasopressin. In the nonpregnant animals, ACTH levels were 5.8 +/- 1.3 at baseline, 6.7 +/- 1.3 after the 0.3-U dose, and 14.6 +/- 2.4 after the 3.0-U dose. The peak ACTH response after each dose of vasopressin was higher in the pregnant animals than in the nonpregnant animals (P less than 0.05). The baseline cortisol level in the pregnant animals was 960 +/- 80 nmol/L and rose to 1370 +/- 110 and 1535 +/- 165 after the 2 doses of vasopressin, respectively. The baseline cortisol concentration in the nonpregnant animals was 910 +/- 86 nmol/L. The cortisol level was 990 +/- 75 after the 0.3-U vasopressin dose and 1380 +/- 140 after the 3.0-U dose. The peak cortisol response after the 0.3-U dose was significantly higher in the pregnant animals (P less than 0.02), while the peak cortisol responses after the 3.0-U dose were similar in the 2 groups of animals. In a single animal, vasopressin was administered sequentially at 4 gestational ages during pregnancy and then 2 times in the postpartum period. The ACTH response to vasopressin increased as pregnancy progressed and then decreased in the postpartum period. In summary, the ACTH and cortisol responses to 0.3 and 3.0 U vasopressin, iv, are enhanced during pregnancy in the baboon, although the responses to exogenous CRH are blunted during gestation. We conclude that the chronic placental CRH stimulation of the pituitary-adrenal axis during pregnancy leads to an enhanced response to vasopressin and a down-regulation of the response to exogenous CRH.
在人类和非人类灵长类动物怀孕期间，促肾上腺皮质激素释放激素（CRH）由胎盘分泌至母体和胎儿循环中。孕期对外源性CRH的促肾上腺皮质激素（ACTH）和皮质醇反应减弱。在本研究中，我们检测了垂体-肾上腺对另一种促肾上腺皮质激素释放因子——血管加压素的反应。研究在长期插管的雌性狒狒身上进行，这些狒狒在其笼舍中自由活动；在4只怀孕动物身上进行了13项研究，在6只未怀孕动物身上进行了8项研究。以两种剂量（0.3和3.0 U）静脉注射血管加压素，并采集血浆样本用于检测CRH、ACTH和皮质醇。结果以平均值±标准误表示。怀孕动物的基线血浆CRH为240±20 pmol/L，未怀孕动物的基线血浆CRH不可测（低于20）。在怀孕动物中，注射0.3 U血管加压素后，ACTH浓度从基线的6.4±1.3 pmol/L升至10.1±0.4，注射3.0 U血管加压素后升至24.9±5.2。在未怀孕动物中，基线ACTH水平为5.8±1.3，注射0.3 U剂量后为6.7±1.3，注射3.0 U剂量后为14.6±2.4。每次注射血管加压素后，怀孕动物的ACTH峰值反应高于未怀孕动物（P<0.05）。怀孕动物的基线皮质醇水平为960±80 nmol/L，注射两种剂量的血管加压素后分别升至1370±110和1535±165。未怀孕动物的基线皮质醇浓度为910±86 nmol/L。注射0.3 U血管加压素后皮质醇水平为990±75，注射3.0 U剂量后为1380±140。怀孕动物注射0.3 U剂量后的皮质醇峰值反应显著更高（P<0.02），而注射3.0 U剂量后两组动物的皮质醇峰值反应相似。在一只动物中，在孕期的4个胎龄依次注射血管加压素，然后在产后注射2次。对血管加压素的ACTH反应随孕期进展而增加，产后则下降。总之，在狒狒孕期，静脉注射0.3和3.0 U血管加压素后，ACTH和皮质醇反应增强，尽管孕期对外源性CRH的反应减弱。我们得出结论，孕期胎盘CRH对垂体-肾上腺轴的慢性刺激导致对血管加压素的反应增强以及对外源性CRH反应的下调。
