Department of Psychology, University of Houston, Houston, USA.
Department of Biology, Stanford University, Stanford, USA.
J Comp Physiol B. 2022 Jan;192(1):107-114. doi: 10.1007/s00360-021-01417-2. Epub 2021 Oct 13.
Steroid hormones play numerous important and diverse roles in the differentiation and development of vertebrate primary and secondary reproductive characteristics. However, the exact role of androgen receptors-which bind circulating androgens-in this regulatory pathway is unclear. Teleost fishes further complicate this question by having two paralogs of the androgen receptor (ARα and ARβ) resulting from a duplication of their ancestral genome. We investigated the functional role of these two ARs on adult testes mass, by eliminating receptor function of one or both paralogs using CRISPR/Cas9 genome edited Astatotilapia burtoni, an African cichlid fish. Fish with two or more functional AR alleles were more likely to be male compared to fish with one or fewer, suggesting that the two paralogs may play redundant roles in the A. burtoni sex determination system. We replicated previous work showing that fish lacking functional ARβ possess testes smaller than wild-type fish, while fish lacking ARα possess testes larger than wild-type fish. However, we found novel evidence supporting a complex relationship between the two AR paralogs in the regulation of testes mass. For instance, the effects of ARα mutation on testes mass are eliminated in homozygous ARβ mutants but the reverse is not true. These results suggest a dynamic relationship between these two AR paralogs where ARβ functions may be permissive to ARα functions in the control of testes mass. This mechanism may contribute to the robust physiological plasticity displayed by A. burtoni and other social teleost fishes.
甾体激素在脊椎动物初级和次级生殖特征的分化和发育中发挥着许多重要且多样化的作用。然而，雄激素受体（结合循环雄激素）在这个调节途径中的确切作用尚不清楚。由于其祖先基因组的重复，鱼类进一步使这个问题复杂化，因为它们有两种雄激素受体（ARα和 ARβ）的同源物。我们通过使用 CRISPR/Cas9 基因组编辑的非洲丽鱼 Astatotilapia burtoni（一种非洲慈鲷鱼）消除一个或两个同源物的受体功能，研究了这两个 AR 对成体睾丸质量的功能作用。与具有一个或更少功能 AR 等位基因的鱼类相比，具有两个或更多功能 AR 等位基因的鱼类更有可能是雄性，这表明这两个同源物在 A. burtoni 性别决定系统中可能发挥冗余作用。我们复制了先前的工作，表明缺乏功能性 ARβ的鱼类的睾丸比野生型鱼类小，而缺乏 ARα的鱼类的睾丸比野生型鱼类大。然而，我们发现了新的证据，支持在调节睾丸质量方面这两个 AR 同源物之间存在复杂的关系。例如，ARα突变对睾丸质量的影响在 ARβ纯合突变体中被消除，但反之则不然。这些结果表明这两个 AR 同源物之间存在动态关系，其中 ARβ的功能可能允许 ARα在控制睾丸质量方面发挥作用。这种机制可能有助于 A. burtoni 和其他社交性鱼类表现出强大的生理可塑性。
