Ozolins I Z, Young I R, McMillen I C
Department of Physiology, Monash University, Clayton, Victoria, Australia.
Endocrinology. 1992 May;130(5):2438-45. doi: 10.1210/endo.130.5.1315243.
We have investigated the ACTH and cortisol responses to acute episodes of hypoxemia or hypoglycemia in fetal sheep in which the hypothalamus and pituitary were surgically disconnected at between 112 and 123 days gestation. Before 130 days gestation, basal plasma concentrations of ACTH were significantly greater in the hypothalamo-pituitary disconnected (HPD) fetuses than in the intact fetal sheep (126-130 days; 105.0 +/- 11.4 ng/liter, HPD group; 64.0 +/- 9.5 ng/liter, intact group). After 130 days, however, there was no difference between plasma ACTH concentrations in the HPD (136-140 days; 154.7 +/- 16.7 ng/liter HPD group; 113.6 +/- 19.1 ng/liter, intact group) and intact fetal sheep, and in both groups the mean ACTH concentrations were significantly greater after 136 days gestation than before 130 days. In the HPD group, however, while the plasma ACTH concentrations were elevated there was no prepartum increase in the plasma concentrations of cortisol. A decrease in the fetal arterial blood PO2 by approximately 50% for 30 min between 123 and 132 days, stimulated a significant increase in fetal ACTH and cortisol concentrations in the intact but not in the HPD fetuses. In the intact group, plasma ACTH concentrations were also significantly increased (P less than 0.001) above control values (98.2 +/- 21.2 ng/liter) at 120 min after the start of an iv infusion of insulin (1 IU/60 min) (517.2 +/- 160.5 ng/liter) and were still elevated at 60 min after the end of the infusion period (1248.1 +/- 643.2 ng/liter). In the HPD fetuses, however, there was no significant change in plasma ACTH concentrations during or after the insulin infusion. In both the HPD and intact groups, there was a significant increase in plasma ACTH concentrations above control values (62.5 +/- 8.5 ng/liter intact; 135.0 +/- 30.6 ng/liter, HPD) after intrafetal administration of CRF (+10 min; 117.5 +/- 8.1 ng/liter, intact; 225.3 +/- 33.1 ng/liter, HPD) indicating that the secretory capacity of the pituitary corticotrophs was not reduced by the HPD procedure. Our results demonstrate that an intact hypothalamic-pituitary connection is required to generate a normal prepartum increase in fetal cortisol concentrations and is essential for an appropriate fetal pituitary-adrenal response to intrauterine hypoxemia and hypoglycemia.
我们研究了妊娠112至123天期间下丘脑和垂体被手术切断连接的胎羊对急性低氧血症或低血糖发作时促肾上腺皮质激素（ACTH）和皮质醇的反应。在妊娠130天之前，下丘脑 - 垂体切断连接（HPD）的胎羊基础血浆ACTH浓度显著高于完整的胎羊（126 - 130天；HPD组为105.0±11.4 ng/升，完整组为64.0±9.5 ng/升）。然而，在130天之后，HPD组（136 - 140天；HPD组为154.7±16.7 ng/升，完整组为113.6±19.1 ng/升）和完整胎羊的血浆ACTH浓度没有差异，并且在两组中，妊娠136天后的平均ACTH浓度均显著高于130天之前。然而，在HPD组中，虽然血浆ACTH浓度升高，但皮质醇的血浆浓度在产前没有增加。在123至132天之间，将胎羊动脉血氧分压降低约50%持续30分钟，刺激完整胎羊而非HPD胎羊的胎儿ACTH和皮质醇浓度显著增加。在完整组中，静脉输注胰岛素（1 IU/60分钟）开始后120分钟时，血浆ACTH浓度也显著高于对照值（98.2±21.2 ng/升）（517.2±160.5 ng/升），并且在输注期结束后60分钟时仍升高（1248.1±643.2 ng/升）。然而，在HPD胎羊中，胰岛素输注期间或之后血浆ACTH浓度没有显著变化。在HPD组和完整组中，胎儿体内注射促肾上腺皮质激素释放因子（CRF）后（+10分钟；完整组为117.5±8.1 ng/升，HPD组为225.3±33.1 ng/升），血浆ACTH浓度均显著高于对照值（完整组为62.5±8.5 ng/升，HPD组为135.0±30.6 ng/升），这表明垂体促肾上腺皮质细胞的分泌能力并未因HPD手术而降低。我们的结果表明，完整的下丘脑 - 垂体连接是胎儿皮质醇浓度在产前正常增加所必需的，并且对于胎儿垂体 - 肾上腺对宫内低氧血症和低血糖的适当反应至关重要。
