Dept. of Pharmacodynamics, University of Florida, 1600 SW Archer Road, Gainesville, FL 32610, USA.
Am J Physiol Endocrinol Metab. 2011 Mar;300(3):E592-9. doi: 10.1152/ajpendo.00560.2010. Epub 2011 Jan 4.
During pregnancy, plasma ACTH and cortisol are chronically increased; this appears to occur through a reset of hypothalamo-pituitary-adrenal (HPA) activity. We have hypothesized that differences in mineralocorticoid receptor activity in pregnancy may alter feedback inhibition of the HPA axis. We tested the effect of MR antagonism in pregnant and nonpregnant ewes infused for 4 h with saline or the MR antagonist canrenoate. Pregnancy significantly increased plasma ACTH, cortisol, angiotensin II, and aldosterone. Infusion of canrenoate increased plasma ACTH, cortisol, and aldosterone in both pregnant and nonpregnant ewes; however, the temporal pattern of these responses differed between these two reproductive states. In nonpregnant ewes, plasma ACTH and cortisol transiently increased at 1 h of infusion, whereas in pregnant ewes the levels gradually increased and were significantly elevated from 2 to 4 h of infusion. MR blockade increased plasma aldosterone from 2 to 4 h in the pregnant ewes but only at 4 h in the nonpregnant ewes. In both pregnant and nonpregnant ewes, the increase in plasma aldosterone was significantly related to the timing and magnitude of the increase in plasma potassium. The results indicate a differential effect of MR activity in pregnant and nonpregnant ewes and suggest that the slow changes in ACTH, cortisol, and aldosterone are likely to be related to blockade of MR effects in the kidney rather than to effects of MR blockade in hippocampus or hypothalamus.
在妊娠期间，血浆 ACTH 和皮质醇会持续升高；这似乎是通过下丘脑-垂体-肾上腺（HPA）活动的重置发生的。我们假设，妊娠期间盐皮质激素受体活性的差异可能会改变 HPA 轴的反馈抑制。我们测试了在接受生理盐水或 MR 拮抗剂坎利酮输注 4 小时的妊娠和非妊娠母羊中，MR 拮抗作用的影响。妊娠显著增加了血浆 ACTH、皮质醇、血管紧张素 II 和醛固酮。坎利酮输注增加了妊娠和非妊娠母羊的血浆 ACTH、皮质醇和醛固酮；然而，这些反应的时间模式在这两种生殖状态之间有所不同。在非妊娠母羊中，血浆 ACTH 和皮质醇在输注的 1 小时内短暂增加，而在妊娠母羊中，水平逐渐增加，并在输注的 2 至 4 小时内显著升高。MR 阻断在妊娠母羊中从 2 小时到 4 小时增加了血浆醛固酮，但在非妊娠母羊中仅在 4 小时增加。在妊娠和非妊娠母羊中，血浆醛固酮的增加与血浆钾增加的时间和幅度显著相关。结果表明，MR 活性在妊娠和非妊娠母羊中具有不同的作用，并表明 ACTH、皮质醇和醛固酮的缓慢变化可能与肾中 MR 效应的阻断有关，而不是与海马或下丘脑的 MR 阻断效应有关。
