Hassan A, Chacko S, Mason D
Department of Zoology, University of Canterbury, Christchurch, New Zealand.
J Endocrinol. 2003 Sep;178(3):491-501. doi: 10.1677/joe.0.1780491.
Following repeated or prolonged exposure to either corticotrophin-releasing hormone (CRH) or arginine vasopressin (AVP), pituitary adrenocorticotrophin (ACTH) responsiveness is reduced. This study compared the characteristics of desensitization to CRH and AVP in perifused ovine anterior pituitary cells. Desensitization to AVP occurred at relatively low AVP concentrations and was both rapid and readily reversible. Treatment for 25 min with AVP at concentrations greater than 2 nM caused significant reductions in the response to a subsequent 5 min 100 nM AVP pulse (IC(50)=6.54 nM). Significant desensitization was observed following pretreatment with 5 nM AVP for as briefly as 5 min. Desensitization was greater following a 10 min pretreatment, but longer exposures caused no further increase. Resensitization was complete within 40 min following 15 min treatment with 10 nM AVP. Continuous perifusion with 0.01 nM CRH had no effect on AVP-induced desensitization. Treatment with 0.1 nM CRH for either 25 or 50 min caused no reduction in the response to a subsequent 5 min stimulation with 10 nM CRH. When the pretreatment concentration was increased to 1 nM significant desensitization was observed, with a greater reduction in response occurring after 50 min treatment. Recovery of responsiveness was progressive following 50 min treatment with 1 nM CRH and was complete after 100 min. Our data show that in the sheep AVP desensitization can occur at concentrations and durations of AVP exposure within the endogenous ranges. This suggests that desensitization may play a key role in regulating ACTH secretion in vivo. If, as has been suggested, CRH acts to set corticotroph gain while AVP is the main dynamic regulator, any change in responsiveness to CRH may significantly influence the overall control of ACTH secretion.
反复或长时间暴露于促肾上腺皮质激素释放激素（CRH）或精氨酸加压素（AVP）后，垂体促肾上腺皮质激素（ACTH）的反应性会降低。本研究比较了灌流培养的绵羊垂体前叶细胞对CRH和AVP脱敏的特征。对AVP的脱敏在相对较低的AVP浓度下即可发生，且迅速且易于逆转。用浓度大于2 nM的AVP处理25分钟会导致对随后5分钟100 nM AVP脉冲的反应显著降低（IC(50)=6.54 nM）。用5 nM AVP预处理仅5分钟后就观察到了显著的脱敏现象。预处理10分钟后脱敏作用更强，但更长时间的暴露并未导致进一步增强。在用10 nM AVP处理15分钟后，40分钟内即可完全恢复敏感性。用0.01 nM CRH持续灌流对AVP诱导的脱敏没有影响。用0.1 nM CRH处理25或50分钟不会导致对随后10 nM CRH刺激5分钟的反应降低。当预处理浓度增加到1 nM时，观察到显著的脱敏现象，50分钟处理后反应降低更明显。用1 nM CRH处理50分钟后反应性逐渐恢复，100分钟后完全恢复。我们的数据表明，在绵羊中，内源性范围内的AVP暴露浓度和持续时间即可导致AVP脱敏。这表明脱敏可能在体内调节ACTH分泌中起关键作用。如果如所提示的那样，CRH起到设定促肾上腺皮质激素细胞增益的作用，而AVP是主要的动态调节因子，那么对CRH反应性的任何变化都可能显著影响ACTH分泌的整体控制。
