McCormick C M, Mahoney E
Neuroscience Program and Department of Psychology, Bates College, Lewiston, Maine, 04240, USA.
Horm Behav. 1999 Feb;35(1):90-101. doi: 10.1006/hbeh.1998.1500.
To explore the role of androgens in early development on adult hypothalamic-pituitary-adrenal (HPA) function in males, we administered flutamide or vehicle injections: (1) to pregnant dams on embryonic days 15-20; (2) to neonatal pups on days 0-5; or (3) to adults on days 55-60. At approximately 70 days of age, trunk blood was collected to determine corticosterone levels (1) upon removal from the home cage, (2) immediately after 30 min of restraint stress, or (3) 60 min after return to home cage following the stressor. Flutamide treatment resulted in higher basal levels of testosterone and stress levels of corticosterone compared to vehicle treatment, and there was no interaction of treatment with age at time of treatment. This suggests that testosterone is less effective at inhibiting HPA function in flutamide-treated males. In addition, prenatally treated males had higher stress levels of corticosterone than neonatally and adult-treated males, regardless of the type of treatment. There were no differences in CBG levels among the groups. The results suggest that, in males, flutamide treatment has a long-lasting effect on HPA function. These results are consistent with our previous research on neonatally gonadectomized males and the hypothesis of organizational effects of sex hormones on HPA function.
为探究雄激素在雄性个体早期发育过程中对成年下丘脑-垂体-肾上腺（HPA）功能的作用，我们进行了氟他胺或溶剂注射：（1）在胚胎期第15至20天对怀孕母鼠进行注射；（2）在出生后第0至5天对新生幼鼠进行注射；或（3）在第55至60天对成年鼠进行注射。在约70日龄时，采集躯干血液以测定皮质酮水平：（1）从饲养笼中取出后；（2）在束缚应激30分钟后立即测定；或（3）在应激源作用后返回饲养笼60分钟后测定。与溶剂处理相比，氟他胺处理导致睾酮的基础水平和皮质酮的应激水平更高，且处理与处理时的年龄之间不存在交互作用。这表明在氟他胺处理的雄性个体中，睾酮抑制HPA功能的效果较差。此外，无论处理类型如何，经产前处理的雄性个体的皮质酮应激水平均高于经新生儿期和成年期处理的雄性个体。各组之间的皮质类固醇结合球蛋白（CBG）水平没有差异。结果表明，在雄性个体中，氟他胺处理对HPA功能具有持久影响。这些结果与我们之前对新生儿期去势雄性个体的研究以及性激素对HPA功能的组织效应假说一致。
