Dias Brian George, Chin Sonia Grace, Crews David
Institute for Neuroscience, University of Texas at Austin, Austin, TX 78712, USA.
Brain Res. 2009 Feb 9;1253:129-38. doi: 10.1016/j.brainres.2008.11.071. Epub 2008 Dec 3.
The steroidogenic enzyme CYP17 is responsible for catalyzing the production of androgenic precursors, while CYP19 converts testosterone to estradiol. De novo neurosteroidogenesis in specific brain regions influences steroid hormone dependent behaviors. In the all-female lizard species Cnemidophorus uniparens, individuals alternately display both male-like mounting and female-like receptivity. Mounting is associated with high circulating concentrations of progesterone following ovulation (PostOv), while receptivity is correlated with estrogen preceding it (PreOv). At a neuroanatomical level, the preoptic area (POA) and ventromedial nucleus of the hypothalamus (VMN) are the foci of the male-typical mounting and female-typical receptivity, respectively. In this study, we indirectly test the hypothesis that the whiptail lizard brain is capable of de novo neurosteroidogenesis by cloning fragments of the genes encoding two steroidogenic enzymes, CYP17 and CYP19, and examining their expression patterns in the C. uniparens brain. Our data indicate that these genes are expressed in the C. uniparens brain, and more importantly in the POA and VMN. Using radioactive in situ hybridization, we measured higher CYP17 mRNA levels in the POA of PostOv lizards compared to receptive PreOv animals; CYP19 mRNA levels in the VMN did not change across the ovarian cycle. To our knowledge, these are the first data suggesting that the reptilian brain is capable of de novo steroidogenesis. This study also supports the idea that non-gonadal sources of steroid hormones locally produced in behaviorally relevant brain loci are central to the mediation of behavioral output.
类固醇生成酶CYP17负责催化雄激素前体的生成,而CYP19则将睾酮转化为雌二醇。特定脑区的从头神经类固醇生成会影响类固醇激素依赖性行为。在全雌性蜥蜴物种独角鞭尾蜥中,个体交替表现出雄性样的骑跨行为和雌性样的接受行为。骑跨行为与排卵后(PostOv)循环中高浓度的孕酮有关,而接受行为则与排卵前(PreOv)的雌激素有关。在神经解剖学水平上,视前区(POA)和下丘脑腹内侧核(VMN)分别是雄性典型骑跨行为和雌性典型接受行为的焦点。在本研究中,我们通过克隆编码两种类固醇生成酶CYP17和CYP19的基因片段,并检查它们在独角鞭尾蜥脑中的表达模式,间接检验了鞭尾蜥脑能够进行从头神经类固醇生成的假设。我们的数据表明,这些基因在独角鞭尾蜥脑中表达,更重要的是在视前区和腹内侧核中表达。使用放射性原位杂交技术,我们测量到与处于接受状态的排卵前动物相比,排卵后蜥蜴视前区的CYP17 mRNA水平更高;腹内侧核中的CYP19 mRNA水平在整个卵巢周期中没有变化。据我们所知,这些是表明爬行动物脑能够进行从头类固醇生成的首批数据。本研究还支持这样一种观点,即在行为相关的脑区局部产生的非性腺来源的类固醇激素对于行为输出的调节至关重要。