Abstract:
Vertebrate sex development consists largely of two processes: \"sex determination,\" the initial bifurcation of sexual identity, and \"sex differentiation,\" which subsequently facilitates maleness or femaleness according to the sex determination signal. Steroid hormones promote multiple types of sexual dimorphism in eutherian mammals and avians [1-3], in which they are indispensable for proper sex differentiation. By contrast, in many poikilothermic vertebrates, steroid hormones have been proposed to be key players in sex determination as well as sex differentiation [4-8]. This hypothesis was introduced more than 50 years ago but has never been rigorously tested due to difficulties in discriminating the roles of steroids in sex determination and differentiation. We found that a missense SNP in the gene encoding the steroidogenic enzyme 17β-hydroxysteroid dehydrogenase 1 (Hsd17b1) was perfectly associated with ZZ/ZW sex determination in Seriola fishes. Biochemical analyses revealed that a glutamate residue present specifically in Z-type HSD17B1 attenuated interconversion between 17-keto and 17β-hydroxy steroids relative to the allelic product from the W chromosome, which harbors glycine at that position, by disrupting the hydrogen bond network between the steroid and the enzyme\'s catalytic residues. Hsd17b1 mRNA is constitutively expressed in undifferentiated and differentiating gonads of both genotypic sexes, whereas W-type mRNA is expressed only in genotypic females. Meanwhile, Cyp19a1 is predominantly expressed in differentiating ovary. We conclude that the combination of Hsd17b1 alleles determines sex by modulating endogenous estrogen levels in Seriola species. These findings strongly support the long-standing hypothesis on steroids in sex determination.
摘要:
脊椎动物的性发育主要包括两个过程:“性别决定,“性认同的最初分歧,和“性别分化,“根据性别确定信号,随后促进男性或女性。类固醇激素促进多种类型的性二态性在优德哺乳动物和禽类[1-3],其中它们对于适当的性别分化是不可或缺的。相比之下,在许多变热脊椎动物中,类固醇激素被认为是性别决定和性别分化的关键角色[4-8]。该假设是在50多年前提出的,但由于难以区分类固醇在性别决定和分化中的作用,因此从未经过严格的测试。我们发现,编码类固醇生成酶17β-羟基类固醇脱氢酶1(Hsd17b1)的基因中的错义SNP与Seriola鱼类的ZZ/ZW性别决定完全相关。生化分析表明,相对于W染色体的等位基因产物,Z型HSD17B1中特异性存在的谷氨酸残基减弱了17-酮和17β-羟基类固醇之间的相互转化,在那个位置有甘氨酸,通过破坏类固醇和酶的催化残基之间的氢键网络。Hsd17b1mRNA在两种基因型性别的未分化和分化性腺中组成型表达,而W型mRNA仅在基因型女性中表达。同时,Cyp19a1主要在分化卵巢中表达。我们得出的结论是,Hsd17b1等位基因的组合通过调节Seriola物种中的内源性雌激素水平来决定性别。这些发现强烈支持了关于类固醇性别决定的长期假设。