Adrenocortical responses to ACTH in neonatal rats: effect of hypoxia from birth on corticosterone, StAR, and PBR.
Adrenocortical responses to ACTH in neonatal rats: effect of hypoxia from birth on corticosterone, StAR, and PBR.
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DOI：
10.1152/ajpregu.00501.2002
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发表时间：
2003
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影响因子：
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通讯作者：
H. Raff;Julie J Hong;M. Oaks;E. Widmaier
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文献类型：
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作者：
H. Raff;Julie J Hong;M. Oaks;E. Widmaier
肾上腺皮质对缺氧的反应可能是适应这种常见的新生儿应激的重要组成部分。对缺氧新生儿体内肾上腺功能知之甚少。本研究的目的是评估肾上腺皮质对ACTH的反应，在哺乳大鼠幼崽暴露于缺氧从出生到5 - 7天的年龄相比，常氧控制。我们还评估了潜在的细胞控制类固醇功能原位。在0800的7日龄幼仔中，出生时的缺氧导致基础（12.2 +/-1.4 ng/ml; n = 12）和ACTH刺激（94.0 +/-9.4 ng/ml; n = 14）皮质酮水平与常氧对照组相比（基础= 8.3 +/-0.5 ng/ml; n = 11;刺激= 51.3 +/-3.8 ng/ml; n = 8）。尽管在注射猪ACTH（20 μ g/kg）之前（85 +/-4 vs. 78 +/-8 pg/ml）或之后（481 +/-73 vs. 498 +/-52 pg/ml），常氧与缺氧幼仔的血浆ACTH水平没有显著差异，但仍发生了这种增加。这种影响在6日龄的下午相似，在5日龄的0800时甚至更大。醛固酮对ACTH的反应并不因出生时暴露于缺氧而增强。RT-PCR检测不到肾上腺皮质缺氧诱导因子（HIF）-1 α mRNA。类固醇生成急性调节（StAR）蛋白在肾上腺subcapsules（束状/网状）增加暴露于缺氧，这种效果是最大的5天的年龄。外周型苯二氮卓受体（PBR）蛋白也增加，在6日龄和7日龄暴露于缺氧从出生的幼崽。我们的结论是，缺氧从出生的结果在增强的皮质酮，但不是醛固酮反应促肾上腺皮质激素。这种效应似乎至少部分由线粒体胆固醇转运控制器（StAR和PBR）的增加介导，并且独立于内源性血浆ACTH的可测量变化而发生。在缺氧的幼崽中，皮质酮对ACTH急性增加的反应增强可能是新生儿对缺氧的整体生理适应的重要组成部分。
The adrenocortical response to hypoxia may be a critical component of the adaptation to this common neonatal stress. Little is known about adrenal function in vivo in hypoxic neonates. The purpose of this study was to evaluate adrenocortical responses to ACTH in suckling rat pups exposed to hypoxia from birth to 5-7 days of age compared with normoxic controls. We also evaluated potential cellular controllers of steroidogenic function in situ. In 7-day-old pups at 0800, hypoxia from birth resulted in increased basal (12.2 +/- 1.4 ng/ml; n = 12) and ACTH-stimulated (94.0 +/- 9.4 ng/ml; n = 14) corticosterone levels compared with normoxic controls (basal = 8.3 +/- 0.5 ng/ml; n = 11; stimulated = 51.3 +/- 3.8 ng/ml; n = 8). This augmentation occurred despite no significant difference in plasma ACTH levels in normoxic vs. hypoxic pups before (85 +/- 4 vs. 78 +/- 8 pg/ml) or after (481 +/- 73 vs. 498 +/- 52 pg/ml) porcine ACTH injection (20 microg/kg). This effect was similar in the afternoon at 6 days of age and even greater at 5 days of age at 0800. The aldosterone response to ACTH was not augmented by exposure to hypoxia from birth. Adrenocortical hypoxia-inducible factor (HIF)-1alpha mRNA was undetectable by RT-PCR. Steroidogenic acute regulatory (StAR) protein in adrenal subcapsules (zona fasciculata/reticularis) was augmented by exposure to hypoxia; this effect was greatest at 5 days of age. Peripheral-type benzodiazepine receptor (PBR) protein was also increased at 6 and 7 days of age in pups exposed to hypoxia from birth. We conclude that hypoxia from birth results in an augmentation of the corticosterone but not aldosterone response to ACTH. This effect appears to be mediated at least in part by an increase in controllers of mitochondrial cholesterol transport (StAR and PBR) and to occur independently of measurable changes in endogenous plasma ACTH. The augmentation of the corticosterone response to acute increases in ACTH in hypoxic pups is likely to be an important component of the overall physiological adaptation to hypoxia in the neonate.