Sex-specific regulation of weight and puberty by the Lin28/let-7 axis.
Sex-specific regulation of weight and puberty by the Lin28/let-7 axis.
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DOI：
10.1530/joe-15-0360
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发表时间：
2016-03
期刊：
影响因子：
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通讯作者：
Palmert MR
中科院分区：
文献类型：
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作者：
Corre C;Shinoda G;Zhu H;Cousminer DL;Crossman C;Bellissimo C;Goldenberg A;Daley GQ;Palmert MR
男孩和女孩的生长和青春期时间不同。在全基因组关联研究中，LIN28B 中/附近的变异与初潮年龄 (AAM) 相关，一些 AAM 相关变异与性别特异性的生长相关。在小鼠中检测到了对 Lin28b 干扰的性别特异性生长模式，并且 Lin28a 的过度表达已被证明会改变雌性小鼠的青春期时间。为了进一步研究 Lin28a 和 Lin28b 如何影响雄性和雌性的生长和青春期，我们评估了 Lin28b 功能丧失 (LOF) 小鼠和 Lin28a 功能获得 (GOF) 小鼠。由于 Lin28a 和 Lin28b 都可以通过保守的 microRNA let-7 发挥作用，因此我们还检查了 let-7 GOF 小鼠。正如之前报道的，Lin28b LOF 仅导致雄性小鼠体重较轻，而 Lin28a GOF 则使雌雄小鼠体重较重。 Let-7 GOF 小鼠的体重低于对照组，并且雄性比雌性受到的影响更大。通过阴道开口（VO）和包皮分离（PS）来评估青春期的时间。雄性 Lin28b LOF 和雄性 let-7 GOF（而非雌性）小鼠表现出青春期时间的改变，PS 晚于对照组。相比之下，雄性和雌性 Lin28a GOF 小鼠均表现出青春期延迟。总之，这些数据表明 Lin28a、Lin28b 和 let-7 存在一个复杂的调节系统，其中 Lin28b 和 let-7 可以以性别特异性的方式影响青春期和生长，这提高了该途径可能有助于人类男性和女性生长和青春期的差异调节的可能性。
Growth and pubertal timing differ in boys and girls. Variants in/near LIN28B associate with age at menarche (AAM) in genome-wide association studies and some AAM-related variants associate with growth in a sex-specific manner. Sex-specific growth patterns in response to Lin28b perturbation have been detected in mice, and overexpression of Lin28a has been shown to alter pubertal timing in female mice. To investigate further how Lin28a and Lin28b affect growth and puberty in both males and females, we evaluated Lin28b loss-of-function (LOF) mice and Lin28a gain-of-function (GOF) mice. Because both Lin28a and Lin28b can act via the conserved microRNA let-7, we also examined let-7 GOF mice. As reported previously, Lin28b LOF led to lighter body weights only in male mice while Lin28a GOF yielded heavier mice of both sexes. Let-7 GOF mice weighed less than controls, and males were more affected than females. Timing of puberty was assessed by vaginal opening (VO) and preputial separation (PS). Male Lin28b LOF and male let-7 GOF, but not female, mice displayed alteration of pubertal timing, with later PS than controls. In contrast, both male and female Lin28a GOF mice displayed late onset of puberty. Together, these data point toward a complex system of regulation by Lin28a, Lin28b, and let-7, in which Lin28b and let-7 can impact both puberty and growth in a sex-specific manner, raising the possibility that this pathway may contribute to differential regulation of male and female growth and puberty in humans.