SEX STEROIDS DO NOT ALTER SEX-DIFFERENCES IN TYROSINE-HYDROXYLASE ACTIVITY OF DOPAMINERGIC-NEURONS INVITRO
SEX STEROIDS DO NOT ALTER SEX-DIFFERENCES IN TYROSINE-HYDROXYLASE ACTIVITY OF DOPAMINERGIC-NEURONS INVITRO
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DOI：
10.1007/bf00645057
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发表时间：
1992-12-01
影响因子：
3.6
通讯作者：
REISERT, I
中科院分区：
文献类型：
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作者：
BEYER, C;EUSTERSCHULTE, B;REISERT, I
为了区分遗传性别和性激素对多巴胺能神经元性分化的影响，在胚胎第14天的大鼠间脑性别特异性培养物中研究了儿茶酚胺的合成。除了来自正常母鼠的胚胎外，还使用了在妊娠第12天和第13天用雌激素拮抗剂他莫昔芬或睾酮拮抗剂醋酸环丙孕酮处理的母鼠的胚胎。每天用含有17 β-雌二醇或睾酮的培养基喂养来自未处理母鼠胚胎的培养物。体外培养10天后，对培养物进行酪氨酸羟化酶免疫染色，并在DOPA脱羧酶抑制剂NSD 1015存在下测量二羟基苯丙氨酸（DOPA）的积累。多巴的合成率，不同的酪氨酸羟化酶免疫反应神经元的数量，在所有实验条件下，女性文化显着较高。在取出胚胎前用抗类固醇药物处理母鼠对这些结果没有影响。两种类固醇治疗的文化减少多巴形成剂量依赖性的方式，而不改变性别差异。这些结果表明，培养的间脑多巴胺能神经元的酪氨酸羟化酶活性存在性别差异。这种两性异形的发生与性腺类固醇激素的作用无关。性激素对这种酶的活性有额外的调节作用，但不能消除或逆转性别差异。因此，哺乳动物大脑性别分化的纯粹表观遗传模式的概念需要扩大到包括其他机制，例如性别特异性遗传程序的细胞自主实现。
In order to distinguish the effects of genetic sex from those of sex hormones on the sexual differentiation of dopaminergic neurons, catecholamine synthesis was studied in gender-specific cultures of embryonic day-14 rat diencephalon. In addition to embryos from normal dams, embryos were used whose mothers had been treated with the estrogen antagonist tamoxifen or the testosterone antagonist cyproterone acetate on days 12 and 13 of gestation. Cultures from embryos of untreated dams were fed daily with a medium containing 17beta-estradiol or testosterone. After 10 days in vitro, cultures were immunostained for tyrosine hydroxylase and the accumulation of dihydroxyphenylalanine (DOPA) was measured in the presence of the DOPA decarboxylase inhibitor NSD 1015. Rates of DOPA synthesis, unlike the numbers of tyrosine hydroxylase-immunoreactive neurons, were markedly higher in female cultures under all experimental conditions. Treatment of dams with antisteroids prior to removal of the embryos had no influence on these results. Treatment of cultures with both steroids decreased DOPA formation in a dose-dependent manner without altering the sex difference. These results suggest that cultured diencephalic dopaminergic neurons develop sex differences in the activity of tyrosine hydroxylase. This sexual dimorphism is initiated independently of the action of gonadal steroid hormones. Sex hormones exert an additional modulatory influence on the activity of the enzyme but do not abolish or reverse sex differences. Therefore, the concept of a purely epigenetic mode of sexual differentiation of the mammalian brain needs to be broadened to incorporate other mechanisms, such as the cell-autonomous fulfillment of a sex-specific genetic program.