Department of Psychology, Faculty of Science, Memorial University of Newfoundland, 232 Elizabeth Ave, St. John's, NL, A1B 3X9, Canada.
Neuroscience Program, Michigan State University, East Lansing, MI, USA.
Arch Sex Behav. 2021 Nov;50(8):3413-3417. doi: 10.1007/s10508-021-02161-y. Epub 2021 Oct 8.
Studying the role of the prenatal endocrine environment in humans is challenging due to the ethical and practical considerations of measuring hormone levels of the developing fetus. Because it has been difficult to ascertain whether prenatal androgens contribute to the brain and behavior in humans as it does in non-human species, retrospective markers of prenatal androgens, such as the second-to-fourth finger digit ratio (2D:4D), are of interest to the studying of human behavioral endocrinology. To assess the validity of such markers, laboratory animals have been studied. Some strains of mice have been reported to show a sex difference in 2D:4D, and pharmacological and genetic manipulation of the androgen and estrogen receptors (AR and ER) has implicated a role for prenatal androgens in mediating this sex difference, although there have been conflicting reports. Here, we compared mice with global AR overexpression to mice with wildtype (WT) littermates and mice with neural-specific AR overexpression. We found a sex difference in the right hind paw, such that males had larger digit ratios than females. Regardless of sex, mice with global AR overexpression showed an increase in the right hind 2D:4D ratio compared with both WT and neural-specific AR overexpression mice. These results support a role for non-neural AR in the development of 2D:4D and suggest that increased sensitivity to androgens via increased AR is sufficient to increase the masculinization of digit ratios. Future directions for confirming the validity of 2D:4D as a marker for prenatal androgen exposure are discussed.
研究人类产前内分泌环境的作用具有挑战性，因为测量发育中胎儿激素水平在伦理和实践上存在考虑。由于难以确定产前雄激素是否像在非人类物种中那样对人类的大脑和行为有贡献，因此，产前雄激素的回溯标志物，如第二到第四指骨长度比（2D:4D），引起了人类行为内分泌学的研究兴趣。为了评估这些标志物的有效性，已经对实验动物进行了研究。据报道，一些品系的老鼠在 2D:4D 上存在性别差异，雄激素和雌激素受体（AR 和 ER）的药理学和遗传操作表明，产前雄激素在介导这种性别差异方面起作用，尽管有相互矛盾的报告。在这里，我们比较了具有全局 AR 过表达的小鼠与具有野生型（WT）同窝仔的小鼠和具有神经特异性 AR 过表达的小鼠。我们发现右后爪存在性别差异，即雄性的指长比大于雌性。无论性别如何，与 WT 和神经特异性 AR 过表达的小鼠相比，具有全局 AR 过表达的小鼠的右后 2D:4D 比值增加。这些结果支持非神经 AR 在 2D:4D 发育中的作用，并表明通过增加 AR 增加对雄激素的敏感性足以增加指长比的男性化。讨论了确认 2D:4D 作为产前雄激素暴露标志物的有效性的未来方向。
