Knockdown of clock genes in the suprachiasmatic nucleus blocks prolactin surges and alters FRA expression in the locus coeruleus of female rats.
Knockdown of clock genes in the suprachiasmatic nucleus blocks prolactin surges and alters FRA expression in the locus coeruleus of female rats.
复制标题
敲除视交叉上核中的时钟基因可阻止催乳素激增并改变雌性大鼠蓝斑中的 FRA 表达。
DOI：
10.1152/ajpendo.00341.2007
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Freeman,MarcE
中科院分区：
文献类型：
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作者：
Poletini,MaristelaO;McKee,De'NiseT;Kennett,JessicaE;Doster,Jamie;Freeman,MarcE
催乳素（PRL）激增所需的视交叉上核（SCN）的昼夜节律信号的性质尚不清楚。由于SCN神经元的昼夜节律是由周期（Per）1，Per 2和昼夜运动输出周期kaput（时钟）基因表达的反馈回路决定的，我们通过破坏这个回路来研究SCN节律性对PRL激增的影响。由于病变的蓝斑（LC）取消PRL浪涌和这些神经元接收SCN的预测，我们调查的作用SCN的节律性在LC神经元的昼夜节律作为一个可能的组成部分的昼夜机制调节PRL浪涌。周期性大鼠在发情前期和雌二醇治疗的卵巢切除大鼠接受注射的反义或随机序列脱氧寡核苷酸鸡尾酒时钟基因（Per1，Per2，和时钟）在SCN，并采取血液样本的PRL测量。酪氨酸羟化酶阳性神经元的百分比Fos相关抗原（FRA）的免疫反应，在卵巢切除大鼠提交的鸡尾酒注射，并在12：12小时的光：暗（LD）或恒定黑暗（DD）的环境。反义鸡尾酒取消了发情前期和雌二醇诱导的PRL浪涌观察下午和增加FRA表达的LC神经元在Zeitgeber时间14 LD和昼夜节律的时间14 DD。由于SCN的传入和传出可能被保存，SCN的节律性是必不可少的，每天在雌性大鼠的PRL激增的幅度，以及LC神经元的昼夜节律。因此，SCN神经元决定PRL分泌激增，可能通过调节LC昼夜神经元活动。
The nature of the circadian signal from the suprachiasmatic nucleus (SCN) required for prolactin (PRL) surges is unknown. Because the SCN neuronal circadian rhythm is determined by a feedback loop ofPeriod (Per) 1, Per2,and circadian locomotor output cycles kaput (Clock) gene expressions, we investigated the effect of SCN rhythmicity on PRL surges by disrupting this loop. Because lesion of the locus coeruleus (LC) abolishes PRL surges and these neurons receive SCN projections, we investigated the role of SCN rhythmicity in the LC neuronal circadian rhythm as a possible component of the circadian mechanism regulating PRL surges. Cycling rats on proestrous day and estradiol-treated ovariectomized rats received injections of antisense or random-sequence deoxyoligonucleotide cocktails for clock genes (Per1, Per2,andClock) in the SCN, and blood samples were taken for PRL measurements. The percentage of tyrosine hydroxylase-positive neurons immunoreactive to Fos-related antigen (FRA) was determined in ovariectomized rats submitted to the cocktail injections and in a 12:12-h light:dark (LD) or constant dark (DD) environment. The antisense cocktail abolished both the proestrous and the estradiol-induced PRL surges observed in the afternoon and the increase of FRA expression in the LC neurons at Zeitgeber time 14 in LD and at circadian time 14 in DD. Because SCN afferents and efferents were probably preserved, the SCN rhythmicity is essential for the magnitude of daily PRL surges in female rats as well as for LC neuronal circadian rhythm. SCN neurons therefore determine PRL secretory surges, possibly by modulating LC circadian neuronal activity.