NEONATAL STRESS - EFFECTS OF HYPOGLYCEMIA AND HYPOXIA ON ADRENAL TYROSINE-HYDROXYLASE GENE-EXPRESSION
NEONATAL STRESS - EFFECTS OF HYPOGLYCEMIA AND HYPOXIA ON ADRENAL TYROSINE-HYDROXYLASE GENE-EXPRESSION
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DOI：
10.1203/00006450-199412000-00006
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发表时间：
1994-12-01
影响因子：
3.6
通讯作者：
LAGAMMA, EF
中科院分区：
文献类型：
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作者：
DECRISTOFARO, JD;LAGAMMA, EF
儿茶酚胺 (CA) 在应激反应中从肾上腺髓质释放并在其中重新合成。在成熟动物中，刺激-分泌-合成耦合通过突触（神经元）活动发生。相反，在未成熟的动物中，在功能性肾上腺神经支配之前，某些应激源（低血糖和血糖减少）不会导致 CA 释放。此外，尚不清楚新生儿的释放和生物合成是否与成人一样保持耦合。因此，为了评估新生儿应激源是否可以在肾上腺神经支配功能之前在基因组水平“直接”诱导CA生物合成，我们研究了酪氨酸羟化酶（TH）基因（CA生物合成中的限速酶）的表达。新生大鼠幼崽要么处于缺氧、低血糖状态，要么处于细胞糖减少状态（2-脱氧葡萄糖）。缺氧应激和胰岛素诱导的低血糖应激均不会改变新生儿 TH mRNA 的稳态水平。然而，细胞糖减少导致 TH mRNA 水平显着升高 2 倍 (p < 0.05)。正如预期的那样，这些应激源均增加了成熟成年大鼠的 TH mRNA 水平。因此，新生儿缺氧和低血糖似乎需要完整的神经源性冲动活动，而细胞血糖减少症可能通过激素机制“直接”诱导 TH RNA。该发育模型允许分析控制肾上腺 CA 释放的机制，与控制 TH RNA 水平生物合成的机制分开。急性新生儿缺氧应激导致肾上腺 CA 释放，但 TH RNA 不增加。慢性产前低氧血症导致的宫内生长迟缓会导致新生儿 CA 耗竭和 CA 反应性下降。我们推测，慢性缺氧会改变 CA 通路，增加这些婴儿对以后应激源的敏感性。
Catecholamines (CA) are released from and resynthesized in the adrenal medulla in response to stress. In the mature animal, stimulus-secretion-synthesis coupling occurs through transsynaptic (neuronal) activity. In contrast, in the immature animal, before functional adrenal innervation, certain stressors (hypoglycemia and glycopenia) do not result in CA release. Additionally, it is not known whether release and biosynthesis remain coupled in the neonate as they are in the adult. Therefore, to evaluate whether neonatal stressors can induce CA biosynthesis at the genomic level ''directly'' before function adrenal innervation, we studied the expression of the tyrosine hydroxylase (TH) gene, the rate-limiting enzyme in CA biosynthesis. Newborn rat pups were made either hypoxic, hypoglycemic, or cellularly glycopenic (2-deoxyglucose). Neither hypoxic stress nor insulin-induced hypoglycemic stress altered steady state levels of TH mRNA in the neonate. However, cellular glycopenia resulted in a significant 2-fold rise in TH mRNA levels (p < 0.05). As expected, each of these stressors increased TH mRNA levels in the mature adult rat. Thus, neonatal hypoxia and hypoglycemia appear to require intact neurogenic impulse activity, whereas cellular glycopenia may ''directly'' induce TH RNA, perhaps through hormonal mechanisms. This developmental model allows for the analysis of mechanisms governing adrenal CA release separate from those governing biosynthesis at the level of TH RNA. Acute neonatal hypoxic stress results in adrenal CA release without increasing TH RNA. Intrauterine growth retardation from chronic prenatal hypoxemia results in neonatal CA depletion and decreased CA responsiveness. We speculate that chronic hypoxia alters CA pathways, increasing the susceptibility of these infants to later stressors.