Cisneros-Larios Brenda, Elias Carol Fuzeti
Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, United States.
Elizabeth W. Caswell Diabetes Institute, University of Michigan, Ann Arbor, MI, United States.
Front Neuroanat. 2023 Jan 6;16:1057727. doi: 10.3389/fnana.2022.1057727. eCollection 2022.
Loss-of-function mutations in prokineticin 2 () and the cognate receptor prokineticin receptor 2 () genes have been implicated in reproductive deficits characteristic of Kallmann Syndrome (KS). Knock out of gene produces the KS-like phenotype in mice resulting in impaired migration of gonadotropin releasing hormone (GnRH) neurons, olfactory bulb dysgenesis, and infertility. Beyond a developmental role, pharmacological and genetic studies have implicated PROKR2 in the control of the estrous cycle in mice. However, PROKR2 is expressed in several reproductive control sites but the brain nuclei associated with reproductive control in adult mice have not been defined. We set out to determine if ProkR2 neurons in both male and female mouse brains directly sense changes in the gonadal steroids milieu. We focused on estrogen receptor α (ERα) and androgen receptor (AR) due to their well-described function in reproductive control actions in the brain. We found that the ProkR2-Cre neurons in the posterior nucleus of the amygdala have the highest colocalization with ERα and AR in a sex-specific manner. Few colocalization was found in the lateral septum and in the bed nucleus of the stria terminalis, and virtually no colocalization was observed in the medial amygdala. Our findings indicate that the posterior nucleus of the amygdala is the main site where PROKR2 neurons may regulate aspects of the reproductive function and social behavior in adult mice.
促动力蛋白2（PROK2）和同源受体促动力蛋白受体2（PROKR2）基因的功能丧失突变与卡尔曼综合征（KS）的生殖缺陷有关。敲除Prok2基因会在小鼠中产生类似KS的表型，导致促性腺激素释放激素（GnRH）神经元迁移受损、嗅球发育不全和不育。除了发育作用外，药理学和遗传学研究表明PROKR2参与小鼠发情周期的调控。然而，PROKR2在多个生殖控制位点表达，但成年小鼠中与生殖控制相关的脑核尚未明确。我们着手确定雄性和雌性小鼠大脑中的ProkR2神经元是否直接感知性腺类固醇环境的变化。由于雌激素受体α（ERα）和雄激素受体（AR）在大脑生殖控制作用中的功能已得到充分描述，我们将重点放在它们身上。我们发现，杏仁核后核中的ProkR2-Cre神经元与ERα和AR的共定位在性别上具有特异性，且比例最高。在外侧隔区和终纹床核中发现的共定位较少，而在内侧杏仁核中几乎未观察到共定位。我们的研究结果表明，杏仁核后核是PROKR2神经元可能调节成年小鼠生殖功能和社会行为的主要部位。
