REGULATION OF CORTICOTROPIN-RELEASING HORMONE-RECEPTOR MESSENGER-RIBONUCLEIC-ACID IN THE RAT-BRAIN AND PITUITARY BY GLUCOCORTICOIDS AND STRESS
REGULATION OF CORTICOTROPIN-RELEASING HORMONE-RECEPTOR MESSENGER-RIBONUCLEIC-ACID IN THE RAT-BRAIN AND PITUITARY BY GLUCOCORTICOIDS AND STRESS
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DOI：
10.1210/en.136.10.4517
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发表时间：
1995-10-01
期刊：
影响因子：
4.8
通讯作者：
GOLD, PW
中科院分区：
文献类型：
--
作者：
MAKINO, S;SCHULKIN, J;GOLD, PW
已知糖皮质激素和应激会影响大脑多个部位促肾上腺皮质激素释放激素（CRH）的合成，包括下丘脑和杏仁核。最近克隆的CRH受体（CRH- r）使我们能够确定糖皮质激素或应激是否通过调节CRH- r来影响CRH的作用。因此，我们就地使用。采用杂交技术检测下丘脑室旁核（PVN）、垂体前叶（AP）、杏仁核和终纹床核（BNST）中CRH-R信使RNA （mRNA）在不同条件下的表达水平。全身皮质酮（CORT）治疗，每日注射（5mg /大鼠）。植入200 mg颗粒14 d后，PVN和杏仁核外侧、基底外侧核（BLA） CRH-R mRNA降低。皮质酮注射液（10mg /大鼠）。肾上腺切除术也降低了PVN和AP中的CRH-R mRNA，但未改变BLA中的CRH-R mRNA。在替换CORT颗粒的假手术和肾上腺切除大鼠（39 mg； ADX + CORT大鼠）中，急性（2小时）和重复（每天2小时，持续14天）固定应激（导致假手术大鼠血浆CORT大量增加）增加了PVN中的CRH-R mRNA，降低了AP中的CRH-R mRNA，但不影响BLA中的CRH-R mRNA。然而，应激后ADX + CORT大鼠在PVN和AP中的CRH-R mRNA水平始终高于假大鼠。脑干半解剖损伤了除蓝斑外的所有上行儿茶酚胺能纤维，减弱了固定应力诱导的PVN中CRH-R mRNA的上调。这些治疗均未影响杏仁核中央和内侧核或BNST的CRH-R mRNA水平。这些结果表明，高浓度CORT或CRH协同降低AP中CRH- r mRNA水平，至少高CORT对PVN CRH- r mRNA水平有抑制作用。然而，应激输入可以克服这种抑制作用，从而上调PVN中的CRH-R mRNA。下丘脑外区域，如杏仁核和BNST可能对CORT或CRH对CRH- r mRNA的调节具有不同的敏感性。
Glucocorticoids and stress are known to influence the synthesis of corticotropin-releasing hormone (CRH) at a variety of sites in brain, including the hypothalamus and amygdala. The recent cloning of the CRH receptor (CRH-R) enabled us to determine whether glucocorticoids or stress influenced CRH action via regulation of CRH-R. We, therefore, used in situ. hybridization to measure CRH-R messenger RNA (mRNA) levels in the hypothalamic paraventricular nucleus (PVN), anterior pituitary (AP), amygdala, and bed nucleus of the stria terminalis (BNST) under several conditions. Systemic corticosterone (CORT) treatment, both daily injection (5 mg/rat . day) up to 14 days and pellet implant (200 mg) for 14 days, decreased CRH-R mRNA in the PVN and lateral and basolateral nucleus of the amygdala (BLA). Corticosterone injection (10 mg/rat . day, for 7 days) decreased CRH-R mRNA in the AP. Adrenalectomy also decreased CRH-R mRNA in the PVN and AP, but did not alter it in the BLA. In both sham and adrenalectomized rats with CORT pellet replacement (39 mg; ADX + CORT rats), acute (2-h) and repeated (2 h daily for 14 days) immobilization stress (which produced a large increase in plasma CORT in sham rats) increased CRH-R mRNA in the PVN and decreased it in the AP, but did not affect CRH-R mRNA in the BLA. However, ADX + CORT rats consistently had higher levels of CRH-R mRNA in both the PVN and AP than sham rats after stress. Brain stem hemisection, which damaged all ascending catecholaminergic fibers with the exception of the locus ceruleus, attenuated immobilization stress-induced up-regulation of CRH-R mRNA ipsilaterally in the PVN. None of the treatments affected CRH-R mRNA levels in the central and medial nucleus of the amygdala or the BNST. These results suggest that high concentrations of CORT or CRH synergistically decrease CRH-R mRNA levels in the AP, and that at least high CORT has an inhibitory effect on PVN CRH-R mRNA levels. However, stress input can override such inhibitory effects and thus up-regulate CRH-R mRNA in the PVN. The extrahypothalamic regions, such as amygdala and BNST may have different sensitivities to CORT or CRH for the regulation of CRH-R mRNA.