REDUCTION OF TYROSINE HYDROXYLASE MRNA EXPRESSION IN MENOPAUSAL MONKEYS

女性的更年期综合征包括潮热， 失眠、抑郁和心血管疾病增加。 这些情况中的每一种都会影响生活质量，其中一种是潜在的 原因可能是儿茶酚胺能神经元功能障碍 多巴胺(DA)、去甲肾上腺素(NE)和肾上腺素 (EPI)。在中年大鼠中，中枢神经NE缺乏症起作用 导致生殖能力下降，学习能力减慢， 减少轮子跑的活动。在灵长类中，人们对此知之甚少 更年期期间和之后大脑化学物质的变化， 其特征是卵巢活动停止，包括 卵巢雌激素(E)和孕激素的产生。我们有 此前有研究表明，成年去卵巢猕猴体内的E基因替换 上调酪氨酸羟化酶(TH，TH)的表达 蓝斑(LC)中去甲肾上腺素(NE)合成限速酶的mRNA 脑干的一种结构，既包含NE细胞体，也包含 多种类型的神经肽。因此，我们假设一个 儿茶酚胺能活性降低，与减少有关 猕猴绝经后，血液中的E_1水平也随之升高。至 检验这一假设，我们检查了三个细胞中TH mRNA的表达 围绝经期(21-25岁)和3岁以下(7-14岁) 年龄)雌性猴子在接受E.治疗后，我们推断 围绝经期猴子体内儿茶酚胺能系统的死亡 改变E.A.恒河猴对TH基因表达的上调 产生猴子特异性TH探针(176bp)，对其进行测序、标记 用S-35涂抹在20米厚的下丘脑和 原位杂交的脑干。TH mRNA阳性信号 将E处理过的老年动物和幼年动物进行数字化比较。 初步数据表明，脑干中的NE细胞 孤束核(A2)，孤束核外侧被盖 延髓(A1)和LC(A6和A4)TH基因表达较少 围绝经期女性多于年轻个体。此外， 围绝经期恒河猴TH基因表达降低 大鼠黑质和外侧被盖内的多巴胺能神经元 中脑。在下丘脑，终纹和 室旁核所含物质较少，而视交叉上核则较少 老年猕猴核内含有较多的TH基因。这些 初步观察结果支持平衡被打破的概念 卵巢E和脑儿茶酚胺能神经元之间的关系 围绝经期的变化。我们计划继续研究这些问题，并 来自相似年龄猴子的其他大脑，并最终发展出一种 用于表征卵巢和中枢神经的猴模型 妇女在绝经前和绝经期间的缺陷。

The menopausal syndrome in women includes hot flashes, sleeplessness, depression and increased cardiovascular difficulties. Each of these conditions impacts quality of life, and one underlying cause may be a malfunctioning of the catecholaminergic neuronal system, i.e., dopamine (DA), norepinephrine (NE) and epinephrine (EPI). In middle-aged rats, central neural NE deficiency contributes to decreased reproductive performance, slowed learning ability and reduced wheel-running activity. In primates, little is known about the changes in brain chemicals during and after onset of menopause, which is characterized by a cessation of ovarian activity, including the production of ovarian estrogens (E) and progestins. We have previously shown that E replacement in adult ovariectomized monkeys up-regulates the expression of tyrosine hydroxylase (TH, the rate-limiting enzyme of NE synthesis) mRNA in the locus coeruleus (LC) of the brainstem a structure that contains both NE cell bodies and multiple types of neuropeptides. Thus, we hypothesize that a reduction of catecholaminergic activity, in association with reduced circulating levels of E, accompanies menopause in rhesus macaques. To test this hypothesis, we examined the expression of TH mRNA in three perimenopausal (21-25 years of age) and three younger (7-14 years of age) female monkeys after treatment with E. We reasoned that the demise of the catecholaminergic system in perimenopausal monkeys would alter the up-regulation of TH gene expression by E. A rhesus monkey-specific TH probe (176 bp) was generated, sequenced, labeled with S-35 and applied to 20 m thin sections of the hypothalamus and brainstem for in situ hybridization. Positive TH mRNA signals were digitized and compared between the E-treated old and young animals. Preliminary data suggest that in the brainstem, the NE cells in the nucleus of the solitary tract (A2), the lateral tegmentum of the medulla (A1) and the LC (A6 and A4) expressed less TH mRNA in the perimenopausal females than in the younger individuals. Furthermore, expression of TH mRNA in the perimenopausal monkeys was reduced in dopaminergic neurons in the substantia nigra and lateral tegmentum of the mesencephalon. In the hypothalamus, the stria terminalis and paraventricular nuclei contained less, whereas the suprachiasmatic nucleus contained more TH mRNA in the older monkeys. These preliminary observations support the concept of a disrupted balance between ovarian E and brain catecholaminergic neurons during perimenopausal changes. We plan to continue the study of these and other brains from similar aged monkeys and ultimately to develop a monkey model for characterization of ovarian and central neural deficits in women before and during onset of menopause.