Stark R I, Wardlaw S L, Daniel S S
Endocrinology. 1986 Aug;119(2):755-61. doi: 10.1210/endo-119-2-755.
To characterize the immunological forms of beta-endorphin (beta-EP) in the fetal circulation, total beta-EP immunoactivity [beta-EPi] and N-acetyl beta-EPi were measured in the plasma of chronically catheterized fetal lambs in undisturbed conditions and before, during, and after periods of controlled hypoxia. Measurements of the peptide concentrations in each plasma sample were made by RIA using an antiserum to the midportion of beta-endorphin which cross-reacts with both acetylated and unacetylated forms of the peptide as well as with beta-lipotropin, and a second antiserum which reacts only with acetylated forms of beta-EP. In 25 plasma samples from 12 fetal animals at 113-142 days gestation, total beta-EPi was 87.0 +/- 10.9 pg/ml, while N-acetyl beta-EPi was 90.8 +/- 7.7 pg/ml (mean +/- SE). When a plasma pool obtained from 3 fetuses in the basal state was extracted and chromatographed on Sephadex G-50, most of the N-acetyl beta-EPi eluted in the same position as the synthetic N-acetyl beta-EP standard. Thus, most of the beta-EPi in the plasma of the unstressed fetus could be accounted for by N-acetylated forms of the peptide. These are the major forms of beta-EP produced by the intermediate lobe of the pituitary. To examine the effects of acute hypoxia on fetal plasma peptide levels, pregnant ewes were exposed to 10% O2 in N2 for 30 min. In 15 studies at 113-142 days gestation, mean fetal PO2 decreased from 21.7 +/- 0.6 to 11.0 +/- 0.7 mm Hg (P less than 0.001). Total beta-EPi increased significantly from 93.0 +/- 17.7 to 527 +/- 146 pg/ml during hypoxia and returned toward basal values after 30 min of recovery to 372 +/- 116 pg/ml (P less than 0.02). Over the same intervals, N-acetyl beta-EPi did not change significantly, with mean levels of 88.5 +/- 10.7, 123 +/- 16.3, and 130 +/- 16.8 pg/ml. This shows that the increase in total beta-EPi with hypoxia could not be accounted for by an increase in N-acetyl beta-EPi. Our finding that most of the total beta-EPi in the circulation of the undisturbed fetus is N-acetyl beta-EPi favors an intermediate lobe origin. Since beta-EP is inactivated by N-acetylation, these data suggest that this immunoactivity has little or no biological activity. Enhanced release of total beta-EPi during hypoxia, which could not be accounted for by acetylated forms, suggests that this type of stress activates the anterior pituitary lobe and results in increased plasma concentrations of the biologically active peptide.
为了描述胎儿循环中β-内啡肽（β-EP）的免疫学形式，在未受干扰的条件下以及在控制性低氧期间和之后，对长期插管的胎羊血浆中的总β-EP免疫活性[β-EPi]和N-乙酰基β-EPi进行了测量。使用针对β-内啡肽中部的抗血清通过放射免疫分析（RIA）对每个血浆样品中的肽浓度进行测量，该抗血清与该肽的乙酰化和未乙酰化形式以及β-促脂素发生交叉反应，还有一种仅与β-EP的乙酰化形式反应的抗血清。在妊娠113 - 142天的12只胎羊的25个血浆样品中，总β-EPi为87.0±10.9 pg/ml，而N-乙酰基β-EPi为90.8±7.7 pg/ml（平均值±标准误）。当从处于基础状态的3只胎儿获得的血浆池进行提取并在Sephadex G - 50上进行色谱分析时，大部分N-乙酰基β-EPi在与合成N-乙酰基β-EP标准品相同的位置洗脱。因此，未受应激的胎儿血浆中的大部分β-EPi可以由该肽的N-乙酰化形式来解释。这些是垂体中间叶产生的β-EP的主要形式。为了研究急性低氧对胎儿血浆肽水平的影响，将怀孕母羊暴露于含10% O₂的N₂中30分钟。在妊娠113 - 142天的15项研究中，胎儿平均动脉血氧分压从21.7±0.6降至11.0±0.7 mmHg（P＜0.001）。在低氧期间，总β-EPi从93.0±17.7显著增加至527±146 pg/ml，并在恢复30分钟后恢复至基础值，为372±116 pg/ml（P＜0.02）。在相同时间段内，N-乙酰基β-EPi没有显著变化，平均水平分别为88.5±10.7、123±16.3和130±16.8 pg/ml。这表明低氧时总β-EPi的增加不能由N-乙酰基β-EPi的增加来解释。我们的发现，即未受干扰的胎儿循环中的大部分总β-EPi是N-乙酰基β-EPi，支持其起源于垂体中间叶。由于β-EP通过N-乙酰化而失活，这些数据表明这种免疫活性几乎没有或没有生物活性。低氧期间总β-EPi的释放增加，而这不能由乙酰化形式来解释，表明这种类型的应激激活了垂体前叶并导致生物活性肽的血浆浓度增加。
