Aguilera Greti, Subburaju Sivan, Young Sharla, Chen Jun
Section on Endocrine Physiology, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA.
Prog Brain Res. 2008;170:29-39. doi: 10.1016/S0079-6123(08)00403-2.
Vasopressin (VP) secreted from parvocellular neurons of the hypothalamic paraventricular nucleus (PVN) stimulates pituitary adrenocorticotropic hormone (ACTH) secretion, through interaction with receptors of the V1b subtype (V1bR) in the pituitary corticotroph, mainly by potentiating the stimulatory effects of corticotrophin-releasing hormone (CRH). Chronic stress paradigms associated with corticotroph hyperresponsiveness lead to preferential expression of hypothalamic VP over CRH and upregulation of pituitary V1bR, suggesting that VP has a primary role during adaptation of the hypothalamic pituitary adrenal (HPA) axis to long-term stimulation. However, studies using pharmacological or genetic ablation of V1bR have shown that VP is required for full ACTH responses to some stressors, but not for the sensitization of ACTH responses to a novel stress observed during chronic stress. Studies using minipump infusion of a peptide V1 antagonist in long-term adrenalectomized rats have revealed that VP mediates proliferative responses in the pituitary. Nevertheless, only a minor proportion of cells undergoing mitogenesis co-express markers for differentiated corticotrophs or precursors, suggesting that new corticotrophs are recruited from yet undifferentiated cells. The overall evidence supports a limited role of VP regulating acute ACTH responses to some acute stressors and points to cell proliferation and pituitary remodelling as alternative roles for the marked increases in parvocellular vasopressinergic activity during prolonged activation of the HPA axis.
从下丘脑室旁核（PVN）的小细胞神经元分泌的血管加压素（VP），通过与垂体促肾上腺皮质激素细胞中V1b亚型受体（V1bR）相互作用，主要是增强促肾上腺皮质激素释放激素（CRH）的刺激作用，来刺激垂体促肾上腺皮质激素（ACTH）的分泌。与促肾上腺皮质激素细胞高反应性相关的慢性应激模式导致下丘脑VP的表达优先于CRH，以及垂体V1bR上调，这表明VP在下丘脑-垂体-肾上腺（HPA）轴适应长期刺激过程中起主要作用。然而，使用V1bR药理学或基因消融的研究表明，VP是ACTH对某些应激源的完全反应所必需的，但不是慢性应激期间观察到的ACTH对新应激反应致敏所必需的。在长期肾上腺切除的大鼠中使用微型泵输注肽V1拮抗剂的研究表明，VP介导垂体中的增殖反应。然而，只有一小部分经历有丝分裂的细胞同时表达分化的促肾上腺皮质激素细胞或前体的标志物，这表明新的促肾上腺皮质激素细胞是从未分化的细胞中招募来的。总体证据支持VP在调节ACTH对某些急性应激源的急性反应中作用有限，并指出细胞增殖和垂体重塑是HPA轴长期激活期间小细胞血管加压素能活性显著增加的替代作用。
