Thomas A, Kim N B, Amico J A
Department of Medicine, University of Pittsburgh School of Medicine, PA 15261, USA.
Brain Res. 1996 Oct 28;738(1):48-52. doi: 10.1016/0006-8993(96)00760-3.
We previously reported that sequential estradiol and progesterone exposure followed by progesterone withdrawal increases oxytocin (OT), but not arginine vasopressin (AVP), messenger ribonucleic acid (mRNA) in the hypothalamic paraventricular nucleus (PVN) of the rat. Substitution of testosterone for progesterone and subsequent testosterone withdrawal in the estrogen-primed rat increases PVN AVP mRNA levels. At the end of pregnancy (day 21), rats are exposed to high estrogen and declining progesterone and testosterone concentrations. Coincident with these changes in circulating gonadal steroid hormones in OT and AVP mRNAs. If progesterone levels are sustained at term, OT levels are attenuated and if testosterone is sustained, AVP mRNA levels are attenuated. Immediately postpartum, however, OT and AVP mRNA levels decline compared to term levels. To further determine the role of estrogen in the regulation of OT and AVP mRNAs, we performed two experiments. In the first experiment, we administered estrogen during the peripartum period to determine if estrogen supplementation prevents the relative attenuation of OT and AVP mRNAs that is seen after parturition. Day 18 pregnant rats were given estradiol-filled or empty capsules and sacrificed on day 2 lactation. By Northern analysis, significant differences in PVN AVP, but not OT, mRNA were found between the estrogen- and sham-treated lactational animals, P < 0.02. In the second experiment, we determined if sustaining estrogen after progesterone is removed in steroid-treated ovariectomized rats is essential for the increase in OT mRNA. Ovariectomized rats were given either empty capsules or sequential estradiol- and progesterone-filled capsules and both were sustained for 12 days. When progesterone-filled capsules were removed, estradiol-filled capsules were either removed or left in place, and the animals were sacrificed 48 h later. PVN OT mRNA was analyzed by Northern blot hybridization. OT mRNA was increased in both of the steroid-treated groups to the same degree, compared to sham-treated animals, P = 0.04. In summary, estrogen supplementation during early lactation prevents the attenuation of PVN AVP, but not OT, mRNA after parturition. In the estrogen-primed ovariectomized rat, it is not necessary to sustain estrogen to see the effects of progesterone withdrawal upon PVN OT mRNA.
我们之前报道过，在大鼠下丘脑室旁核（PVN）中，序贯给予雌二醇和孕酮，随后撤去孕酮会增加催产素（OT）的信使核糖核酸（mRNA）水平，但不会增加精氨酸加压素（AVP）的mRNA水平。在经雌激素预处理的大鼠中，用睾酮替代孕酮，随后撤去睾酮会增加PVN中AVP的mRNA水平。在妊娠末期（第21天），大鼠会暴露于高雌激素以及逐渐下降的孕酮和睾酮浓度环境中。这些循环性腺类固醇激素的变化与OT和AVP的mRNA变化同时发生。如果足月时孕酮水平持续维持，OT水平会减弱；如果睾酮持续维持，AVP的mRNA水平会减弱。然而，与足月时相比，产后即刻OT和AVP的mRNA水平会下降。为了进一步确定雌激素在调节OT和AVP的mRNA中的作用，我们进行了两项实验。在第一个实验中，我们在围产期给予雌激素，以确定补充雌激素是否能防止产后出现的OT和AVP的mRNA相对减弱现象。给妊娠第18天的大鼠植入含雌二醇或不含药物的胶囊，并在哺乳期第2天处死。通过Northern分析发现，在接受雌激素处理和假处理的哺乳期动物之间，PVN中AVP的mRNA存在显著差异，但OT的mRNA无显著差异，P<0.02。在第二个实验中，我们确定在经类固醇处理的去卵巢大鼠中，在撤去孕酮后持续给予雌激素对于OT的mRNA增加是否至关重要。给去卵巢大鼠植入不含药物或序贯含雌二醇和孕酮的胶囊，并持续12天。当撤去含孕酮的胶囊时，将含雌二醇的胶囊要么撤去要么留在原位，48小时后处死动物。通过Northern印迹杂交分析PVN中OT的mRNA。与假处理的动物相比，两个经类固醇处理的组中OT的mRNA均增加到相同程度，P = 0.04。总之，在哺乳早期补充雌激素可防止产后PVN中AVP的mRNA减弱，但不能防止OT的mRNA减弱。在经雌激素预处理的去卵巢大鼠中，无需持续给予雌激素就能观察到撤去孕酮对PVN中OT的mRNA的影响。
