Kalogeras K T, Nieman L K, Friedman T C, Doppman J L, Cutler G B, Chrousos G P, Wilder R L, Gold P W, Yanovski J A
Clinical Neuroendocrinology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Clin Invest. 1996 May 1;97(9):2045-50. doi: 10.1172/JCI118640.
Arginine vasopressin (AVP) acts synergistically with corticotropin-releasing hormone (CRH) to stimulate ACTH release from the anterior pituitary. In a previous study of bilateral simultaneous inferior petrosal sinus (IPS) sampling in healthy human subjects, we observed lateralized ACTH secretion, suggesting lateralized secretion of an ACTH-regulating hypothalamic factor. To investigate this possibility, we measured ACTH, CRH, AVP, and oxytocin (OT) levels in the IPS and the peripheral circulation in nine normal volunteers, before and after 1 microgram/kg i.v. bolus ovine CRH (oCRH). At baseline, ACTH, AVP, and OT exhibited a significant (P < 0.05) two to threefold intersinus gradient (ISG), indicating the existence of a dominant petrosal sinus. Endogenous CRH was undetectable in all samples. Despite similar exogenous oCRH levels in both petrosal sinuses, oCRH caused a significant increase (P < 0.001) in the ACTH ISG (15.8 +/- 5.6, mean +/- SEM), suggesting increased responsiveness of one dominant side of the anterior pituitary. This was associated with an ipsilateral CRH-induced AVP release and a significant increase (P < 0.01) in the AVP ISG (8.6 +/- 2.3), suggesting lateralized AVP secretion by the hypothalamus. Furthermore, the increased AVP ISG after oCRH correlated strongly with the ACTH ISG (r = 0.92, P < 0.01). oCRH administration did not affect OT. These findings suggest that there is a dominant petrosal sinus in healthy volunteers that appears to reflect a dominant side of the adenohypophysis, characterized by increased functional activity and/or responsiveness of the pituitary corticotrophs. This may reflect lateralized hypothalamic and/or suprahypothalamic function resulting in CRH-responsive lateralized secretion of AVP from parvocellular and/or magnocellular axons in the median eminence and the posterior pituitary. Although the functional and teleologic significance of these findings remains to be investigated, our data suggest a novel mechanism for CRH-mediated ACTH release, namely CRH-induced release of AVP which then enhances CRH action on the corticotrophs. Furthermore, our data represent the first direct evidence for the concept of brain lateralization with respect to neuroendocrine secretion.
精氨酸加压素（AVP）与促肾上腺皮质激素释放激素（CRH）协同作用，刺激垂体前叶释放促肾上腺皮质激素（ACTH）。在之前一项对健康人类受试者进行双侧同时性岩下窦（IPS）采样的研究中，我们观察到ACTH分泌存在侧化现象，提示存在一种调节ACTH的下丘脑因子的侧化分泌。为了探究这种可能性，我们在9名正常志愿者静脉推注1微克/千克羊CRH（oCRH）前后，测量了IPS和外周循环中的ACTH、CRH、AVP和催产素（OT）水平。在基线时，ACTH、AVP和OT呈现出显著（P < 0.05）的两到三倍的窦间梯度（ISG），表明存在一个优势岩下窦。在所有样本中均未检测到内源性CRH。尽管两个岩下窦中的外源性oCRH水平相似，但oCRH使ACTH的ISG显著增加（P < 0.001）（15.8 +/- 5.6，平均值 +/- 标准误），提示垂体前叶优势侧的反应性增强。这与同侧CRH诱导的AVP释放以及AVP的ISG显著增加（P < 0.01）（8.6 +/- 2.3）相关，提示下丘脑存在AVP的侧化分泌。此外，oCRH后AVP的ISG增加与ACTH的ISG密切相关（r = 0.92，P < 0.01）。给予oCRH不影响OT。这些发现表明，健康志愿者中存在一个优势岩下窦，它似乎反映了腺垂体的优势侧，其特征是垂体促肾上腺皮质细胞的功能活性和/或反应性增强。这可能反映了下丘脑和/或下丘脑以上结构的侧化功能，导致来自正中隆起和垂体后叶的小细胞和/或大细胞轴突对CRH产生反应的AVP侧化分泌。尽管这些发现的功能和目的学意义仍有待研究，但我们的数据提示了一种CRH介导的ACTH释放的新机制，即CRH诱导AVP释放，然后增强CRH对促肾上腺皮质细胞的作用。此外，我们的数据代表了关于神经内分泌分泌的脑侧化概念的首个直接证据。
