Diurnal variation in resting levels of corticosterone is not mediated by variation in adrenal responsiveness to adrenocorticotropin but involves splanchnic nerve integrity

Diurnal variation in resting levels of corticosterone is not mediated by variation in adrenal responsiveness to adrenocorticotropin but involves splanchnic nerve integrity
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DOI:
10.1210/en.137.2.540
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发表时间:
1996-02-01
期刊:
影响因子:
4.8
通讯作者:
Tilders, FJH
Tilders, FJH
中科院分区:
医学2区
文献类型:
--
作者:
Dijkstra, I;Binnekade, R;Tilders, FJH

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为了研究控制皮质酮(CORT)水平昼夜变化的可能机制,我们测试了雄性Wistar和Sprague-Dawley大鼠CORT在早上(AM)和晚上(PM)对ACTH的反应。将大鼠ACTH-(1-39)或人ACTH-(1-24) (3.75 ~ 15 ng/大鼠)作为静脉滴注或动脉滴注给(未)麻醉的地塞米松治疗大鼠(0.1 ~ 0.5 mg/kg, ACTH前2 ~ 6 h)。在所有研究条件下,当ACTH在车辆(pH 4.3-7)中给予时,没有发现AM/PM对CORT反应的差异。这与早期在强酸载体(pH 1-1.9)中给予ACTH的研究形成对比。在这种酸性车辆中给予ACTH证实了报道的AM/PM在CORT反应中的差异(P < 0.05)。由于内脏神经活动的改变可以调节acth诱导的CORT分泌,我们研究了内脏神经横断(SPLNX)对单侧肾上腺切除大鼠静息时CORT水平日变化的影响。SPLNX降低了PM的静息CORT浓度(接近50%;P < 0.05),但在AM中没有。SPLNX并没有消除与酸性载体相关的CORT对ACTH反应的AM/PM差异。我们得出结论:1)在该大鼠模型中,肾上腺对ACTH的反应性本身不存在日变化;2)强酸载体与acth诱导的CORT分泌相互作用;3)血浆CORT的PM升高取决于交感神经输入肾上腺的完整性。
To study possible mechanisms controlling diurnal changes in corticosterone (CORT) levels, we tested the CORT responses to ACTH in the morning (AM) and evening (PM) in male Wistar and Sprague-Dawley rats. Rat ACTH-(1-39) or human ACTH-(1-24) (3.75-15 ng/rat) was given as an iv bolus or an intraarterial infusion to (un)anesthetized rats treated with dexamethasone (0.1-0.5 mg/kg, 2-6 h before ACTH). In all conditions studied, no AM/PM differences in CORT responses were found when ACTH was given in vehicle (pH 4.3-7). This contrasts with earlier studies in which ACTH was given in a strongly acid vehicle (pH 1-1.9). Administration of ACTH in such acid vehicle confirmed the reported AM/PM differences in CORT responses (P < 0.05). Because alterations in splanchnic nerve activity can modulate ACTH-induced CORT secretion, we studied the effect of splanchnic nerve transection (SPLNX) on the diurnal change in resting CORT levels in unilaterally adrenalectomized rats. SPLNX reduced resting CORT concentrations in the PM(similar to 50%; P < 0.05), but not in the AM. SPLNX did not abolish the acid vehicle-associated AM/PM differences in CORT responses to ACTH. We conclude that 1) diurnal variation in adrenal responsiveness to ACTH per se does not exist in this rat model; 2) the strongly acid vehicle interacts with ACTH-induced CORT secretion; 3) the PM rise in plasma CORT depends on the integrity of the sympathetic neural input to the adrenal gland.