Zelena D, Mergl Z, Makara G B
Hungarian Academy of Sciences, Institute of Experimental Medicine, Budapest, Hungary.
J Neuroendocrinol. 2003 Dec;15(12):1105-10. doi: 10.1111/j.1365-2826.2003.01101.x.
The role of vasopressin, cosecreted with corticotropin-releasing hormone (CRH), in stress is debated, because both normal as well as reduced adrenocorticotropin hormone (ACTH) rise to an acute challenge has been reported in Brattleboro rats genetically lacking vasopressin (di/di). Because di/di pups could be born either from di/+ (heterozygous) or from di/di mothers, and maternal influence is known to modify adult responsiveness, we investigated whether the influence of maternal genotype could explain the variability. Adult rats from mothers with different genotypes were stressed with 60 min restraint and trunk blood was collected for measuring hormone content by radioimmunoassay at the end of stress. All offspring of di/+ mothers had similar ACTH responses to restraint, while the di/di rats born to, and raised by di/di mothers showed reduced ACTH reactivity to restraint. The di/di rats showed elevated water turnover and required a daily cage cleaning every day, which meant frequent handling. To offset the role of handling, all rats had daily cage cleaning in the next series, but the results were the same as in the first series. To investigate whether lactation, the behaviour of the mother or some other factor during the pregnancy is responsible for the differences, pups from di/+ dams were raised by di/di foster mothers and vice versa. We found that the genotype of parental mother is more important than that of the foster mother. The corticosterone and prolactin elevation normally seen after acute stress was unchanged by family history, maternal or personal genotype. Furthermore, in studies with mutant animals, the rearing conditions should be controlled by the experimenter. In experiments with Brattleboro rats, the use of homozygous and heterozygous rats from the same litters of di/+ dams and di/di males is recommended. Our results suggest that vasopressin is not indispensable for ACTH release, and that the di/di genotype of the parental mother can decrease the stress reactivity of the di/di Brattleboro rats.
与促肾上腺皮质激素释放激素（CRH）共同分泌的血管升压素在应激反应中的作用存在争议，因为据报道，遗传性缺乏血管升压素的布拉特洛维大鼠（di/di）对急性刺激的促肾上腺皮质激素（ACTH）升高反应正常或降低。由于di/di幼崽可能由di/+（杂合子）或di/di母亲所生，且已知母体影响会改变成年后的反应性，我们研究了母体基因型的影响是否可以解释这种变异性。将来自不同基因型母亲的成年大鼠进行60分钟的束缚应激，应激结束时采集躯干血，通过放射免疫分析法测定激素含量。di/+母亲的所有后代对束缚的ACTH反应相似，而由di/di母亲生育并抚养长大的di/di大鼠对束缚的ACTH反应性降低。di/di大鼠的水周转率升高，每天都需要清洁笼子，这意味着频繁处理。为了抵消处理的影响，在下一系列实验中所有大鼠都进行了每日笼内清洁，但结果与第一系列相同。为了研究是哺乳期、母亲的行为还是怀孕期间的其他因素导致了这些差异，将di/+母鼠的幼崽由di/di代孕母亲抚养，反之亦然。我们发现，亲生母亲的基因型比代孕母亲的基因型更重要。急性应激后通常出现的皮质酮和催乳素升高不受家族史、母体或个体基因型的影响。此外，在对突变动物的研究中，饲养条件应由实验者控制。在使用布拉特洛维大鼠的实验中，建议使用来自同一窝di/+母鼠和di/di雄鼠的纯合子和杂合子大鼠。我们的结果表明，血管升压素对于ACTH释放并非不可或缺，并且亲生母亲的di/di基因型可降低di/di布拉特洛维大鼠的应激反应性。
