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首页> 外文期刊>Endocrinology >Prenatal Influence of an Androgen Agonist and Antagonist on the Differentiation of the Ovine Sexually Dimorphic Nucleus in Male and Female Lamb Fetuses
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Prenatal Influence of an Androgen Agonist and Antagonist on the Differentiation of the Ovine Sexually Dimorphic Nucleus in Male and Female Lamb Fetuses

机译:雄激素激动剂和拮抗剂对产羔羊胎儿性别双态核分化的影响

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The ovine sexually dimorphic nucleus (oSDN) is 2 times larger in rams than in ewes. Sexual differentiation of the oSDN is produced by testosterone exposure during the critical period occurring between gestational day (GD) 60 and GD90 (term, 147 d). We tested the hypothesis that testosterone acts through the androgen receptor to control development of the male-typical oSDN. In experiment 1, pregnant ewes received injections of vehicle, androgen receptor antagonist flutamide, or nonaromatizable androgen dihydrotestosterone (DHT) propionate during the critical period. Fetuses were delivered at GD135. Both antagonist and agonist treatments significantly reduced mean oSDN volume in males but had no effects in females. Experiment 2, we analyzed the effect of treatments on the fetal hypothalamic-pituitary-gonadal axis to determine whether compensatory changes in hormone secretion occurred that could explain the effect of DHT. Pregnant ewes were injected with vehicle, flutamide, or DHT propionate from GD60 to GD84, and fetuses were delivered on GD85. Flutamide significantly increased LH and testosterone in males, whereas DHT significantly decreased both hormones. In females, LH was unaffected by flutamide but significantly reduced by DHT exposure. DHT significantly decreased pituitary gonadotropin and hypothalamic kisspeptin mRNA expression in males and females. These results suggest that androgen receptor mediates the effect of testosterone on oSDN masculinization, because this process was blocked by the androgen receptor antagonist flutamide in eugonadal males. In contrast, the reduction of oSDN volume observed after DHT exposure appears to be mediated by a negative feedback mechanism exerted on the hypothalamus to reduce LH and testosterone secretion. The reduced androgen exposure most likely accounted for the decreased oSDN volume. We conclude that, during the critical period, the male reproductive axis in long gestation species, such as sheep, is sufficiently developed to react to perturbations in serum androgens and mitigate disruptions in brain masculinization.
机译:公羊的绵羊性二态核(oSDN)比母羊大2倍。 oSDN的性别分化是通过在妊娠第60天至GD90(第147天)之间的关键时期暴露于睾丸激素而产生的。我们测试了睾丸激素通过雄激素受体控制男性典型oSDN发育的假设。在实验1中,怀孕的母羊在关键时期接受了媒介物,雄激素受体拮抗剂氟他胺或不可芳香化的雄激素二氢睾丸激素(DHT)丙酸酯的注射。胎儿以GD135分娩。拮抗剂和激动剂治疗均显着降低了男性的平均oSDN量,但对女性没有影响。实验2,我们分析了治疗对胎儿下丘脑-垂体-性腺轴的影响,以确定激素分泌是否发生代偿性变化,这可以解释DHT的影响。妊娠母羊注射了从GD60到GD84的赋形剂,氟他胺或DHT丙酸酯,并以GD85注射了胎儿。氟他胺显着增加男性的LH和睾丸激素,而DHT显着降低两种激素。在女性中,LH不受氟他胺的影响,但因DHT暴露而明显降低。 DHT明显降低了男性和女性的垂体促性腺激素和下丘脑基索肽mRNA的表达。这些结果表明,雄激素受体介导睾丸激素对oSDN男性化的作用,因为在成年男性中,雄激素受体拮抗剂flutamide阻止了这一过程。相反,DHT暴露后观察到的oSDN体积的减少似乎是由施加于下丘脑以减少LH和睾丸激素分泌的负反馈机制所介导的。减少的雄激素暴露很可能是oSDN量减少的原因。我们得出的结论是,在关键时期,长期繁殖物种(例如绵羊)中的雄性生殖轴已充分发育,可以对血清雄激素的干扰做出反应,并减轻大脑男性化的破坏。

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