González-Flores Oscar, Ramírez-Orduña Juan Manuel, Lima-Hernández Francisco Javier, García-Juárez Marcos, Beyer Carlos
Centro de Investigación en Reproducción Animal, CINVESTAV-Universidad Autónoma de Tlaxcala, Mexico.
Horm Behav. 2006 Mar;49(3):398-404. doi: 10.1016/j.yhbeh.2005.08.011. Epub 2005 Oct 27.
Dose response curves for lordosis behavior was obtained for progesterone (P) and its two ring A-reduced metabolites: 5alpha-pregnanedione (alpha-DHP) and 5alpha,3alpha-pregnanolone (5alpha,3alpha-Pgl) by infusing these progestins in the right lateral ventricle (rlv) of ovariectomized (ovx) estradiol-treated rats (2 microg estradiol benzoate; EB), 40 h before intracerebro-ventricular (icv) injection. Effective doses 50 (ED50) revealed that ring A-reduced progestins were more potent than P itself to induce lordosis behavior. Two dose levels, one producing the maximal effect and the other one producing a submaximal response (ED50-ED60), were selected for testing the capacity of RpAMPS, a kinase A blocker, and H7, a kinase C blocker, to modify the response to the three progestins. rlv injection of RpAMPS significantly depressed the lordosis response to the two dose levels of P and alpha-DHP but failed to significantly inhibit that of 5alpha,3alpha-Pgl. The administration of H7 prevented the effect of both 5alpha-reduced progestins without affecting the response to P. The results suggest that P and its ring A-reduced metabolites stimulate lordosis behavior through different cellular mechanisms: P acting mainly through the cAMP-kinase system; alpha-DHP through both kinase A and kinase C signaling pathways and 5alpha,3alpha-Pgl through the kinase C system.
通过将这些孕激素注入去卵巢（ovx）并经雌二醇处理的大鼠（2微克苯甲酸雌二醇；EB）的右侧脑室（rlv），在脑室内（icv）注射前40小时，获得了孕酮（P）及其两种A环还原代谢物：5α-孕烷二酮（α-DHP）和5α,3α-孕烷醇酮（5α,3α-Pgl）对脊柱前凸行为的剂量反应曲线。半数有效剂量（ED50）显示，A环还原的孕激素比P本身更能有效诱导脊柱前凸行为。选择两个剂量水平，一个产生最大效应，另一个产生次最大反应（ED50-ED60），以测试蛋白激酶A阻滞剂RpAMPS和蛋白激酶C阻滞剂H7改变对这三种孕激素反应的能力。rlv注射RpAMPS显著降低了对两个剂量水平的P和α-DHP的脊柱前凸反应，但未能显著抑制5α,3α-Pgl的反应。给予H7可阻止两种5α-还原孕激素的作用，而不影响对P的反应。结果表明，P及其A环还原代谢物通过不同的细胞机制刺激脊柱前凸行为：P主要通过cAMP-激酶系统起作用；α-DHP通过激酶A和激酶C信号通路起作用，而5α,3α-Pgl通过激酶C系统起作用。
