Canny B J, Young I R, Veldhuis J D
Department of Physiology, Monash University, Clayton, Victoria, Australia.
Endocrinology. 1998 Jul;139(7):3210-9. doi: 10.1210/endo.139.7.6086.
A prepartum increase in fetal glucocorticoid concentrations is essential for the perinatal transition to extrauterine life for many mammalian species. In the case of the sheep, this increase in cortisol is also the trigger for parturition, and depends upon an intact hypothalamo-pituitary unit. Fetal sheep that have undergone hypothalamo-pituitary disconnection (HPD) fail to have a prepartum cortisol surge or initiate labor, despite apparently normal fetal ACTH concentrations in late gestation. We have investigated whether a defect exists in the regulation of pulsatile neurohormone secretion in the pituitaryadrenal axis of the HPD sheep fetus, by comparing immunoreactive (ir) ACTH and cortisol secretory dynamics in intact and HPD fetuses at 126 and 145 days of gestation (normal gestation length, 147 days). The fetal surgery was conducted at 115 days of gestation. Blood samples were collected at 5-min intervals for 2 h on each experimental day, and the resulting irACTH and cortisol concentrations were analyzed by multiple-parameter deconvolution and cross-correlation analysis. Basal irACTH secretion was less (P < 0.01) in HPD fetuses than intact fetuses at 126 days, but it had recovered by 145 days. There were no differences in irACTH half-life or the number or duration of irACTH secretory bursts between the two groups of fetuses or the two gestational ages (GAs). The size of the irACTH secretory bursts was not affected by the operation, but it increased with GA to a similar extent in both groups of fetuses (P < 0.01). In keeping with the observations for irACTH secretion, there was no effect of age or the operation on cortisol half-life or on the number or duration of cortisol secretory bursts. In contrast, there were dramatic age-related increases (P < 0.01) in the basal cortisol secretion rate and the size of the cortisol secretory bursts in the intact, but not the HPD, fetuses. Cross-correlation analysis revealed a significant (P < 0.01) concordance between irACTH and cortisol secretion in only the intact fetuses at 126 days; this was not apparent in the intact fetuses at 145 days, or in the young or old HPD fetuses. These findings confirm a major defect in cortisol secretion in the late-gestation HPD fetus but suggest that this is not caused by defects in irACTH secretion. Together with other observations, these data suggest that ACTH may not be the sole, or primary, regulator of adrenal cortisol secretion in the late-gestation ovine fetus.
对于许多哺乳动物物种而言，产前胎儿糖皮质激素浓度的升高对于围产期向宫外生活的转变至关重要。就绵羊而言，皮质醇的这种升高也是分娩的触发因素，并且依赖于完整的下丘脑 - 垂体单位。尽管妊娠晚期胎儿促肾上腺皮质激素（ACTH）浓度看似正常，但经历了下丘脑 - 垂体切断术（HPD）的绵羊胎儿却未能出现产前皮质醇激增或启动分娩。我们通过比较妊娠126天和145天（正常妊娠期为147天）时完整胎儿和HPD胎儿中免疫反应性（ir）ACTH和皮质醇的分泌动态，研究了HPD绵羊胎儿垂体 - 肾上腺轴中脉冲式神经激素分泌调节是否存在缺陷。胎儿手术在妊娠115天时进行。在每个实验日，每隔5分钟采集一次血样，共采集2小时，然后通过多参数反卷积和互相关分析对所得的irACTH和皮质醇浓度进行分析。在126天时，HPD胎儿的基础irACTH分泌量低于完整胎儿（P < 0.01），但到145天时已恢复。两组胎儿以及两个胎龄（GAs）之间，irACTH半衰期、irACTH分泌脉冲的数量或持续时间均无差异。irACTH分泌脉冲的大小不受手术影响，但在两组胎儿中均随胎龄增加，且增加程度相似（P < 0.01）。与irACTH分泌的观察结果一致，年龄或手术对皮质醇半衰期、皮质醇分泌脉冲的数量或持续时间均无影响。相比之下，完整胎儿而非HPD胎儿的基础皮质醇分泌率和皮质醇分泌脉冲大小随年龄有显著增加（P < 0.01）。互相关分析显示，仅在126天的完整胎儿中，irACTH和皮质醇分泌之间存在显著的（P < 0.01）一致性；在145天的完整胎儿中，以及年轻或年老的HPD胎儿中均未观察到这种一致性。这些发现证实了妊娠晚期HPD胎儿皮质醇分泌存在主要缺陷，但表明这并非由irACTH分泌缺陷所致。与其他观察结果一起，这些数据表明ACTH可能不是妊娠晚期绵羊胎儿肾上腺皮质醇分泌的唯一或主要调节因子。
