School of Aquatic and Fishery Sciences, University of Washington, Seattle, Washington, USA.
Department of Biological Science, California State University, Fullerton, Fullerton, California, USA.
Biol Reprod. 2017 Nov 1;97(5):731-745. doi: 10.1093/biolre/iox124.
Recent studies using several teleost models have revealed that androgens increase the size of previtellogenic (primary and/or early secondary) ovarian follicles. To explore our hypothesis that androgens drive the development of primary follicles into early secondary follicles, and to determine the mechanisms underlying these androgenic effects, we exposed juvenile coho salmon to near-physiological and relatively sustained levels of the nonaromatizable androgen 11-ketotestosterone (11-KT). This resulted in significant growth of primary ovarian follicles after 10 and 20 days, with follicles after 20 days displaying a morphological phenotype characteristic of early secondary follicles (presence of cortical alveoli). Utilizing the same experimental approach, we then analyzed how 11-KT rapidly altered the ovarian transcriptome after 1 and 3 days of treatment. RNA-Seq analysis revealed that 69 (day 1) and 1,022 (day 3) contiguous sequences (contigs) were differentially expressed relative to controls. The differentially expressed contigs mapped to genes including those encoding proteins involved in gonadotropin, steroid hormone, and growth factor signaling, and in cell and ovarian development, including genes with putative androgen-response elements. Biological functions and canonical pathways identified as potentially altered by 11-KT include those involved in ovarian development, tissue differentiation and remodeling, and lipid metabolism. We conclude that androgens play a major role in stimulating primary ovarian follicle development and the transition into secondary growth.
最近使用几种硬骨鱼类模型的研究表明，雄激素可使卵原细胞期（初级和/或早期次级）的卵巢卵泡增大。为了验证我们的假设，即雄激素促使初级卵泡发育为早期次级卵泡，并确定这些雄激素作用的机制，我们让幼年银大麻哈鱼接触接近生理的、相对持续的非芳香化雄激素 11-酮睾酮（11-KT）。这导致初级卵巢卵泡在 10 天和 20 天后显著生长，20 天后的卵泡呈现出早期次级卵泡的形态表型（存在皮质小泡）。利用相同的实验方法，我们分析了 11-KT 在处理 1 天和 3 天后如何快速改变卵巢转录组。RNA-Seq 分析显示，与对照组相比，有 69 个（第 1 天）和 1022 个（第 3 天）连续序列（contigs）差异表达。差异表达的 contigs 映射到编码与促性腺激素、类固醇激素和生长因子信号以及细胞和卵巢发育相关的蛋白质的基因，包括具有潜在雄激素反应元件的基因。11-KT 可能改变的生物学功能和经典途径包括与卵巢发育、组织分化和重塑以及脂质代谢相关的途径。我们得出结论，雄激素在刺激初级卵巢卵泡发育和向次级生长过渡中起着重要作用。
