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大鼠孕期最后一周暴露于乙醇:抑制雄性大鼠产前睾酮激增,且性行为无长期改变。

Ethanol exposure during the last week of gestation in the rat: inhibition of the prenatal testosterone surge in males without long-term alterations in sex behavior.

作者信息

McGivern R F, Handa R J, Raum W J

机构信息

San Diego State University, Department of Psychology, CA, USA.

出版信息

Neurotoxicol Teratol. 1998 Jul-Aug;20(4):483-90. doi: 10.1016/s0892-0362(98)00009-9.

Abstract

In utero ethanol exposure decreases the prenatal testosterone (T) surge in male rats. To determine the functional significance of this suppression, we measured sex behavior in adult litter representatives of pregnant rats that were administered a fortified liquid diet containing 35% ethanol-derived calories from day 15 of gestation through parturition. Control dams were pair-fed an isocaloric liquid diet with the ethanol calories replaced by sucrose. Results from the behavioral studies showed that gonadally intact fetal alcohol-exposed (FAE) males exhibited little masculine sex behavior in the first of four weekly sessions. However, their behavior in the subsequent three tests was indistinguishable from pair-fed controls. Lordosis quotients in the same males following castration and estrogen and progesterone treatment were under 10%. In castrated FAE females, no effects of prenatal ethanol exposure were observed in masculine behaviors following androgen replacement or feminine sex behaviors following estrogen and progesterone replacement. Additional studies measured the duration of prenatal ethanol exposure necessary to inhibit the prenatal T surge in order to determine whether the inhibition was due to a direct effect of the drug. Results revealed an inhibition of the surge in males exposed to ethanol from days 14 through 20 of pregnancy, days 14 through 16 of pregnancy, or days 17 through 20 of pregnancy. A normal surge of T was observed on days 18-19 of gestation in control fetuses. These findings indicate that ethanol does not have to be present in blood at the time of the surge to have an inhibitory effect. They also reveal that the surge can be inhibited with as little as 24-36 h of ethanol exposure prior to its normal appearance on day 18 of gestation. In spite of this inhibition of the prenatal T surge, the behavioral results indicate that normal masculinization and defeminization of sex behavior occurs in FAE males exposed to ethanol after the beginning of the period of differentiation of the hypothalamus and testes.

摘要

子宫内乙醇暴露会降低雄性大鼠产前睾酮(T)的激增。为了确定这种抑制作用的功能意义,我们对妊娠大鼠的成年同窝仔鼠进行了性行为测量,这些妊娠大鼠从妊娠第15天到分娩期间给予强化液体饮食,其中35%的热量来自乙醇。对照母鼠成对喂食等热量液体饮食,用蔗糖替代乙醇热量。行为学研究结果表明,性腺完整的胎儿酒精暴露(FAE)雄性在四周一次的测试中的第一次测试中几乎没有表现出雄性性行为。然而,它们在随后的三次测试中的行为与成对喂食的对照组没有区别。相同雄性大鼠去势后以及接受雌激素和孕酮治疗后的脊柱前凸商低于10%。在去势的FAE雌性大鼠中,产前乙醇暴露对雄激素替代后的雄性性行为或雌激素和孕酮替代后的雌性性行为均未产生影响。其他研究测量了抑制产前T激增所需的产前乙醇暴露持续时间,以确定这种抑制是否是由于药物的直接作用。结果显示,在妊娠第14天至20天、第14天至16天或第17天至20天暴露于乙醇的雄性大鼠中,T激增受到抑制。对照胎儿在妊娠第18 - 19天观察到T的正常激增。这些发现表明,在T激增时血液中不一定需要存在乙醇才能产生抑制作用。它们还表明,在妊娠第18天正常出现T激增之前,仅暴露24 - 36小时的乙醇就能抑制T激增。尽管产前T激增受到抑制,但行为学结果表明,在下丘脑和睾丸分化期开始后暴露于乙醇的FAE雄性大鼠中,性行为的正常雄性化和去雌性化仍会发生。

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