Fast glucocorticoid feedback inhibition of ACTH secretion in the ovariectomized rat: effect of chronic estrogen and progesterone.
Fast glucocorticoid feedback inhibition of ACTH secretion in the ovariectomized rat: effect of chronic estrogen and progesterone.
复制标题
去势大鼠中 ACTH 分泌的快速糖皮质激素反馈抑制：慢性雌激素和孕激素的作用。
DOI：
10.1159/000126741
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发表时间：
1994
影响因子：
4.1
通讯作者：
Aird,F
中科院分区：
文献类型：
--
作者：
Redei,E;Li,L;Halasz,I;McGivern,RF;Aird,F
本研究的目的是确定雌激素和孕酮是否影响糖皮质激素对ACTH和皮质酮(CORT)应激反应的快速负反馈调节。成年大鼠摘除卵巢，6周后植入17β-雌二醇(E_2，0.5 mg)、E_2和孕酮(P，100 mg；E_2+P组)或安慰剂颗粒(OVX)。7d后，给予单次或多次间歇性足底电击应激(0.2 mA，15 S持续时间，0.5 S持续时间)。重复应激的强度和持续时间相同，要么在血浆皮质醇水平上升时(第一次应激开始后5min)的速率敏感型快速糖皮质激素反馈的时间域内施加，要么在对初始应激的皮质醇反应达到峰值时(15min)施加。连续采血测定血浆ACTH和CORT。在卵巢切除动物中，雌激素单独替代或与黄体酮联合使用可降低对单一应激的即时(t=5)ACTH和CORT反应。OVX组和E_2+P替代激素组在初始应激后5分钟施加第二次应激后产生的ACTH净反应与单次应激后相似，而E_2处理组的总ACTH反应较低。在去卵巢的动物中，在15分钟后的足底电击中，当整合的ACTH分泌明显大于单次电击后的反应或相隔5分钟的重复电击后，先前的应激对ACTH的反应明显促进。与OVX组相比，E2或E2+P替代组的垂体前阿片黑素皮质素(POMC)基因表达水平降低。相比之下，下丘脑促肾上腺皮质激素释放因子(CRF)的mRNA水平并没有显著增加。然而，17β-雌二醇治疗后，下丘脑糖皮质激素受体(GR)基因表达增加，这种增加被黄体酮逆转。这些结果表明，先前的应激既会导致快速反馈抑制，也会促进随后的应激反应。在没有性腺激素的情况下，这种促进作用被糖皮质激素快速反馈时间域中的快速反馈抑制所平衡，并且在该时间域之外被揭开。雌激素抑制POMC信使核糖核酸的合成，导致可释放的ACTH的可获得性降低，从而降低促进作用。孕酮可能通过降低快速速率敏感型糖皮质激素负反馈的疗效来对抗雌激素的这种影响。
The purpose of this study was to determine whether estrogen and progesterone influence fast glucocorticoid negative feedback regulation of the ACTH and corticosterone (CORT) responses to stress. Mature rats were ovariectomized and 6 weeks later implanted with 17β-estradiol (E2,0.5 mg), E2and progesterone (P, 100 mg; E2+P group) or placebo pellets (OVX). Seven days later rats were subjected to a single or repeated intermittent footshock stress (0.2 mA, 15 s duration, 0.5 s on). The repeated stress was of the same intensity and duration, and was applied either during the time domain of the rate-sensitive fast glucocorticoid feedback when plasma CORT levels are rising (5 min after the onset of the first stress), or at the time of peak CORT response (15 min) to the initial stress. Plasma ACTH and CORT were measured from serial samples. Estrogen replacement alone or in combination with progesterone lowered the immediate (t = 5) ACTH and CORT response to a single stress in ovariectomized animals. The second stress applied 5 min after the initial stress produced net ACTH responses similar to those obtained after a single stress in the OVX and E2+P-replaced hormone groups, while total ACTH responses were lower in the E2-treated group. In ovariectomized animals, a facilitation of ACTH response by a prior stress is apparent in response to a footshock 15 min later, when the integrated ACTH secretion is significantly greater than the response measured after a single shock, or after a repeated shock 5 min apart. Anterior pituitary proopiomelanocortin (POMC) mRNA levels were lower in groups with E2or E2+P replacement compared to OVX animals. In contrast, hypothalamic corticotropin-releasing factor (CRF) mRNA levels did not increase significantly. However, hypothalamic glucocorticoid receptor (GR) mRNA levels increased after 17β-estradiol treatment, and this increase was reversed by progesterone. These results suggest that prior stress leads to both a fast-feedback inhibition and a facilitation of the subsequent stress response. In the absence of gonadal hormones this facilitation is balanced by fast-feedback inhibition during the glucocorticoid fast-feedback time domain, and is unmasked outside of this time domain. Estrogen suppresses POMC mRNA synthesis leading to a decrease in the availability of releasable ACTH, thereby reducing the facilitation. Progesterone may counter this effect of estrogen by decreasing the efficacy of the fast rate-sensitive glucocorticoid negative feedback.