Hippocampal and hypothalamic type I corticosteroid receptor affinities are reduced in adult rats born by a caesarean procedure with or without an added period of anoxia
Hippocampal and hypothalamic type I corticosteroid receptor affinities are reduced in adult rats born by a caesarean procedure with or without an added period of anoxia
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DOI：
10.1159/000127094
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发表时间：
1996-07-01
影响因子：
4.1
通讯作者：
Sharma, S
中科院分区：
文献类型：
--
作者：
Boksa, P;Krishnamurthy, A;Sharma, S
临产和分娩期间短暂的缺氧是经常发生的。在中枢神经系统内，已知成年和未成熟动物的海马体特别容易受到缺氧/缺血的破坏性影响。海马还含有所有脑区中浓度最高的皮质类固醇受体，海马中的盐皮质激素（I 型）受体和糖皮质激素（II 型）受体在调节基础昼夜和应激诱导的糖皮质激素分泌中发挥作用。鉴于此背景，本研究的目的是测试出生过程中的急性缺氧期是否可能对中枢神经系统皮质类固醇受体水平和/或垂体肾上腺皮质功能产生持久影响。比较了顺产、剖腹产或剖腹产加缺氧 5、10 或 15 分钟的成年大鼠海马和下丘脑的 I 型和 II 型皮质类固醇受体结合位点。使用 14 nM [H-3] 皮质酮作为放射性配体，与阴道出生的对照相比，通过剖腹产手术出生的成年大鼠（无论有或没有增加缺氧期）的海马和下丘脑中的盐皮质激素受体结合减少了约 50%。饱和度分析表明，这些减少是由于盐皮质激素受体对[H-3]皮质酮的亲和力降低所致，而受体数量没有变化。出生条件对海马或下丘脑的糖皮质激素受体结合能力没有影响。在剖腹产出生的成年动物中，在缺氧 5 或 15 分钟的情况下，观察到基础皮质酮分泌在昼间低谷期间略有增加。与阴道出生的对照组相比，无论是否增加缺氧期，剖腹产出生的成年动物的血浆皮质酮对 20 分钟束缚应激的反应均降低。然而，促肾上腺皮质激素对压力的反应在很大程度上不受出生条件的影响。结果表明，急性出生损伤足以在海马和下丘脑盐皮质激素受体位点产生持久的改变，并伴随基础糖皮质激素分泌和应激诱导的糖皮质激素分泌的变化。
Brief periods of hypoxia during labour and birth are a frequent occurrence. Within the CNS, the hippocampus is known to be particularly vulnerable to the damaging effects of hypoxia/ischaemia in both adult and immature animals. The hippocampus also contains the highest concentration of corticosteroid receptors of any brain region and both mineralocorticoid (type I) receptors and glucocorticoid (type II) receptors in the hippocampus play a role in the regulation of basal diurnal and stress-induced glucocorticoid secretion. Given this background, the aim of this study was to test whether an acute period of anoxia during the birth process may have lasting effects on CNS corticosteroid receptor levels and/or pituitary-adrenocortical function. Type I and type II corticosteroid receptor binding sites in the hippocampus and hypothalamus were compared in adult rats that had been born vaginally, born by a Caesarean procedure or born by a Caesarean procedure with 5, 10 or 15 min of added anoxia. Using 14 nM [H-3]corticosterone as radioligand, mineralocorticoid receptor binding was reduced by approximately 50% in the hippocampus and hypothalamus of adult rats that had been born by the Caesarean procedure either with or without an added period of anoxia, in comparison to vaginally born controls. Saturation analysis revealed that these reductions resulted from decreases in affinity of the mineralocorticoid receptor for [H-3]corticosterone, with no change in numbers of receptors. Birth condition had no effect on glucocorticoid receptor binding capacities in the hippocampus or hypothalamus. A small increase in basal corticosterone secretion during the diurnal trough was observed in adult animals that had been born by Caesarean section with 5 or 15 min of added anoxia. The plasma corticosterone response to a 20-min restraint stress was reduced in adult animals born by Caesarean section with or without an added period of anoxia, in comparison to vaginally born controls. However the adrenocorticotropin response to stress was largely unaffected by birth condition. The results indicate that an acute birth insult is sufficient to produce long-lasting alterations in hippocampal and hypothalamic mineralocorticoid receptor sites, accompanied by changes in basal and stress-induced glucocorticoid secretion.