Proliferation and apoptosis in the human adrenal cortex during the fetal and perinatal periods: implications for growth and remodeling.
Proliferation and apoptosis in the human adrenal cortex during the fetal and perinatal periods: implications for growth and remodeling.
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DOI：
10.1210/jcem.84.3.5513
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发表时间：
1999-03
期刊：
影响因子：
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通讯作者：
S. Spencer;Sam Mesiano;Janet Y. Lee;Robert B. Jaffe
中科院分区：
文献类型：
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作者：
S. Spencer;Sam Mesiano;Janet Y. Lee;Robert B. Jaffe
在妊娠10-15周后，由于被称为胎儿区（FZ）的专门皮质区室的扩大，人胎儿肾上腺皮质经历快速生长。出生后不久，FZ退化，并且成人带状图案至少部分地由来自持久限定区（DZ）的细胞发展，持久限定区是FZ周围的一层紧密堆积的细胞。我们假设胎儿肾上腺皮质的生长涉及特定区域的细胞增生，而出生后退化的FZ是由于细胞凋亡。因此，我们研究了在FZ和DZ的人胎儿和出生后的肾上腺皮质细胞增殖和死亡的模式，使用增殖细胞核抗原作为有丝分裂的标志物和原位检测的DNA片段作为凋亡的标志物的免疫组化染色。在妊娠10-14周之间，DZ（26.46 +/- 2.95%）和FZ（21.26 +/- 2.57%）的有丝分裂指数（增殖细胞核抗原阳性细胞的百分比）没有显著差异。孕15-20周，两个区域的有丝分裂指数（FZ，33.84 ± 5.21%; DZ，67.45 ± 7.58%）均较孕15周前显著增加（P < 0.05）。妊娠21-24周之间持续增加（FZ，39.5 +/- 4.22%; DZ，58.63 +/- 6.83%）。有趣的是，14周后，DZ的有丝分裂指数显著高于FZ（P < 0.05）。在早产儿的肾上腺标本中，宫内用糖皮质激素治疗后，FZ和DZ的有丝分裂指数显著降低。在妊娠的所有阶段，在DZ中均未检测到凋亡细胞核。然而，在FZ的中心部分检测到散在的凋亡细胞核。内FZ的凋亡细胞核的数量随着妊娠的进展而增加，并在出生后的第一个月达到最大值。为了鉴定可能调节细胞凋亡的因素，用激活素A和转化生长因子β（TGF β）处理妊娠中期FZ细胞的原代培养物。激活素A和TGF β均诱导凋亡性细胞死亡，如通过核小体间DNA切割（DNA梯状化）所评估的。激活素A诱导的细胞凋亡被同时加入卵泡抑素（一种激活素结合蛋白）阻止。总之，这些数据表明：1）人胎儿肾上腺皮质的生长涉及细胞增生，主要在DZ中，在FZ中程度较低，这可能依赖于ACTH;和2）细胞凋亡主要发生在内皮质区室中，可能是出生后FZ快速消退的原因，这一过程可能受激活素A和/或TGF β调节。
After 10-15 weeks of gestation, the human fetal adrenal cortex undergoes rapid growth due to enlargement of a specialized cortical compartment known as the fetal zone (FZ). Soon after birth, the FZ regresses and the adult zonation pattern develops at least in part from cells derived from the persistent definitive zone (DZ), a thin layer of tightly packed cells surrounding the FZ. We postulated that growth of the fetal adrenal cortex involves zone-specific cellular hyperplasia, whereas the postnatal involution of the FZ is due to apoptosis. Therefore, we investigated the pattern of cellular proliferation and death in the FZ and DZ of the human fetal and postnatal adrenal cortex using immunohistochemical staining for proliferating cell nuclear antigen as a marker of mitosis and in situ detection of DNA fragmentation as a marker of apoptosis. Between 10-14 weeks' gestation, the mitotic indexes (percentage of proliferating cell nuclear antigen-positive cells) in the DZ (26.46 +/- 2.95%) and in the FZ (21.26 +/- 2.57%) were not significantly different. Between 15-20 weeks gestation, the mitotic index increased significantly (P < 0.05) in both zones (FZ, 33.84 +/- 5.21%; DZ, 67.45 +/- 7.58%) relative to levels before 15 weeks. This increase persisted between 21-24 weeks gestation (FZ, 39.5 +/- 4.22%; DZ, 58.63 +/- 6.83%). Interestingly, after 14 weeks, the mitotic index of the DZ was significantly greater (P < 0.05) than that of the FZ. In adrenal specimens obtained from infants born prematurely and treated in utero with glucocorticoid, the mitotic indexes in the FZ and DZ were significantly decreased. At all stages of gestation, no apoptotic nuclei were detected in the DZ. However, scattered apoptotic nuclei were detected in the central portions of the FZ. The number of apoptotic nuclei in the inner FZ increased with advancing gestation and was maximal during the first postnatal month. To identify factors that may regulate apoptosis, primary cultures of midgestation FZ cells were treated with activin A and transforming growth factor-beta (TGFbeta). Activin A and TGFbeta both induced apoptotic cell death, as assessed by internucleosomal DNA cleavage (DNA laddering). Induction of apoptosis by activin A was prevented by concomitant addition of follistatin, an activin-binding protein. Taken together, these data indicate that 1) growth of the human fetal adrenal cortex involves cellular hyperplasia, mainly in the DZ and to a lesser extent in the FZ, which is probably dependent on ACTH; and 2) apoptosis occurs predominantly in the inner cortical compartment and may be responsible for the rapid regression of the FZ after birth, a process that may be regulated by activin A and/or TGFbeta.