Johnson Karl, Bruder Eric D, Raff Hershel
Endocrine Research Laboratory, Aurora Research Institute, Aurora St. Luke's Medical Center Milwaukee, Wisconsin ; Department of Medicine, Surgery, and Physiology, Medical College of Wisconsin Milwaukee, Wisconsin.
Physiol Rep. 2013 Aug;1(3):e00054. doi: 10.1002/phy2.54. Epub 2013 Aug 22.
We have previously demonstrated that the neonatal corticosterone response to acute hypoxia shifts from ACTH independence to ACTH dependence between postnatal days two (PD2) and eight (PD8). Cyclic AMP (cAMP) is the obligatory intracellular second messenger of ACTH action, and we hypothesized that corticosterone production in neonatal rats shifts from a cAMP-independent mechanism to cAMP-dependent mechanism between PD2 and PD8. Plasma ACTH and corticosterone and adrenal cAMP and cGMP responses to acute severe hypoxia (8% O2 for 5, 10, 20, 30, and 180 min) were measured in neonatal rats at PD2, PD8, and PD15. Plasma ACTH and corticosterone were measured by radioimmunoassay, and adrenal cAMP and cGMP were measured by ELISA. Plasma corticosterone-binding globulin (CBG) was measured in normoxic pups by ELISA. The largest corticosterone response was observed in PD2 pups, despite only a small increase in plasma ACTH that was not sustained. The PD2 ACTH-independent increase in corticosterone occurred with no change in adrenal cAMP or cGMP content. Plasma CBG concentration was lowest in PD2 pups. Large corticosterone responses were measured during the first 30 min of hypoxia. Differences in corticosterone responses between PD2 and PD8 pups cannot be attributed to changes in plasma protein binding capacity, and the PD2 corticosterone response is consistent with a nongenomic mechanism of action. We conclude that the sustained corticosterone response to hypoxia in PD2 pups occurs with small and transient ACTH responses and independently of increases in adrenal cAMP or cGMP.
我们之前已经证明，新生大鼠对急性缺氧的皮质酮反应在出生后第2天（PD2）和第8天（PD8）之间从不依赖促肾上腺皮质激素（ACTH）转变为依赖ACTH。环磷酸腺苷（cAMP）是ACTH作用所必需的细胞内第二信使，我们推测新生大鼠的皮质酮产生在PD2和PD8之间从cAMP非依赖机制转变为cAMP依赖机制。在PD2、PD8和PD15的新生大鼠中，测量了血浆ACTH和皮质酮以及肾上腺cAMP和cGMP对急性严重缺氧（8%氧气，持续5、10、20、30和180分钟）的反应。通过放射免疫测定法测量血浆ACTH和皮质酮，通过酶联免疫吸附测定法测量肾上腺cAMP和cGMP。通过酶联免疫吸附测定法在常氧幼崽中测量血浆皮质酮结合球蛋白（CBG）。尽管血浆ACTH仅小幅增加且未持续，但在PD2幼崽中观察到最大的皮质酮反应。PD2时皮质酮不依赖ACTH的增加伴随着肾上腺cAMP或cGMP含量无变化。PD2幼崽的血浆CBG浓度最低。在缺氧的前30分钟内测量到较大的皮质酮反应。PD2和PD8幼崽之间皮质酮反应的差异不能归因于血浆蛋白结合能力的变化，并且PD2的皮质酮反应与非基因组作用机制一致。我们得出结论，PD2幼崽对缺氧的持续皮质酮反应是在ACTH反应小且短暂的情况下发生的，并且与肾上腺cAMP或cGMP的增加无关。
