Lustig R H
Department of Pediatrics, University of Wisconsin, Madison 53792, USA.
Horm Behav. 1994 Dec;28(4):383-95. doi: 10.1006/hbeh.1994.1035.
The sex hormonal milieu during human and primate development is thought to influence adult cognition, perception, and behavior. Similarly in the rat, the neonatal sex hormonal milieu dictates adult behavior, as well as patterns of neural organization within the CNS. Specifically, estrogen and androgen alter neurite outgrowth, neuritic spine development, and synaptogenesis in the limbic system and spinal cord. To examine specific molecular/cellular effects of sex hormones on neurons, in vitro models were developed, using the PC12 cell line. Wild-type cells (PC12-WT) were stably transfected either with an expression vector coding for the human estrogen receptor (ER), androgen receptor (AR), or with a control vector. Resultant clones were isolated, screened for incorporation of vector and expression of ER or AR mRNA and protein, and analyzed for morphologic responses to estrogen and androgen, respectively. PC12-WT, NEO9 (ER-negative, AR-negative), SER8 (ER-positive, AR-negative), and AR8 (ER-negative, AR-positive) cells were exposed to nerve growth factor and graded doses of estradiol or dihydrotestosterone (DHT) for 2 days. In SER8 cells, estradiol led to dose-dependent increases in the frequency of neurite outgrowth, spine development, and interneuritic connectivity. Estradiol increased the frequency of gap junction frequency and length, and functional dye-coupling in SER8 cells. Conversely, in AR8 cells, DHT induced a dose-dependent increase in mean neurite length, branch order, and neuritic field area, while neurite branch segment length and soma area were unaffected. These results suggest that SER8 and AR8 cells in vitro recapitulate various sex hormonal effects on neurons in vivo. Estrogen and androgen appear to induce inherent neural morphologic programs in which androgen increases neurite arborization and the receptive field of individual cells, increasing the likelihood for intercellular communication, while estrogen actually induces this communication, in the form of spines, synapses, and gap junctions. Thus estrogen and androgen act in different but complementary ways to modulate neural development and organization.
人类和灵长类动物发育过程中的性激素环境被认为会影响成年后的认知、感知和行为。同样，在大鼠中，新生期的性激素环境决定成年后的行为以及中枢神经系统内的神经组织模式。具体而言，雌激素和雄激素会改变边缘系统和脊髓中的神经突生长、神经棘发育以及突触形成。为了研究性激素对神经元的特定分子/细胞效应，利用PC12细胞系建立了体外模型。野生型细胞（PC12-WT）用编码人雌激素受体（ER）、雄激素受体（AR）的表达载体或对照载体进行稳定转染。分离得到所得克隆，筛选载体整合情况以及ER或AR mRNA和蛋白的表达情况，并分别分析其对雌激素和雄激素的形态学反应。将PC12-WT、NEO9（ER阴性、AR阴性）、SER8（ER阳性、AR阴性）和AR8（ER阴性、AR阳性）细胞暴露于神经生长因子以及不同剂量的雌二醇或二氢睾酮（DHT）中2天。在SER8细胞中，雌二醇导致神经突生长频率、棘突发育和神经突间连接性呈剂量依赖性增加。雌二醇增加了SER8细胞中缝隙连接的频率和长度以及功能性染料偶联。相反，在AR8细胞中，DHT诱导平均神经突长度、分支顺序和神经突区域面积呈剂量依赖性增加，而神经突分支节段长度和胞体面积未受影响。这些结果表明，体外的SER8和AR8细胞概括了体内性激素对神经元的各种效应。雌激素和雄激素似乎诱导了内在的神经形态学程序，其中雄激素增加神经突分支和单个细胞的感受野，增加细胞间通讯的可能性，而雌激素实际上以棘突、突触和缝隙连接的形式诱导这种通讯。因此，雌激素和雄激素以不同但互补的方式调节神经发育和组织。
