NEURAL INFLUENCE ON HYPOPHYSEAL GONADAL FUNCTION

神经对垂体性腺功能的影响

• 批准号: 6453705
• 负责人: HAROLD G SPIES
• 金额: $ 11.11万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-01 至 2002-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6453705
• 关键词: Mammalia; aging; animal tissue; clinical research; endocrine gland /system; hormones; lipids; nervous system; nucleic acids; proteins; reproductive system; structural biology; women's health

The preovulatory release of gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) in women and rhesus monkeys is dependent upon enhanced secretion of ovarian estradiol-17? (E). This E-induced GnRH/LH surge is accompanied by changes in hypothalamic and brainstem cells that are identified as neuropeptide Y (NPY)-, norepinephrine (NE)-, acetylcholine (Ach)- and gamma aminobutyric acid (GABA)-containing neurons. Our research has focused on how E influences transcriptional-translational events associated with these peptide and transmitter systems and how these central neural events change with aging, especially the perimenopausal life-stage where E secretion declines. Two isoforms of the E receptor (ER ? and ?) have been reported. To study the tissue distribution of the ER isoforms, we cloned and sequenced two cDNA probes (126 bp and 291 bp) for rhesus monkey ER-?. These cDNA fragments were similar, but not identical, to human ER-? sequences. With pro bes for bo th ER-? and ER-?, we quantified the ER isoforms in several peripheral and central neural male and female tissues by reverse transcription-polymerase chain reaction (RT-PCR). Both the ER-? and ER-? mRNAs were present in male and female reproductive organs. Only ER-? was expressed in liver, frontal cortex, caudate nucleus, locus coeruleus and cerebellum. In some brain regions, i.e., the putamen, internal capsule, hippocampus and paraventricular hypothalamus, ER-? was expressed in the female, but not in the male. In macaque females 10-15 years of age mRNA expression for tyrosine hydroxylase (TH, enzyme for control of NE synthesis) in specific adrenergic neural populations (A1, A2, A6) are upregulated by E treatment. However, after E treatment in perimenopausal monkeys (> 22 years old), expression levels of TH mRNA is dampened in the A6 region of brainstem. We continue to study the relevance of this age- and E-related decline in TH mRNA response in brainstem neurons. We also cloned a 356 bp monkey choline acetyltransferase (CHAT, the enzyme for control of Ach synthesis) cDNA fragment that corresponds to the human CHAT N-1 type sequence 332 to 684. The 5= and 3= primer sequences were TAAGATGGCAGCAAAAACTCCC and ACCGATGACCAGCTGAGGTTT, respectively. To our knowledge, this partial DNA sequence of the rhesus monkey CHAT gene has not been documented previously. The MCHAT RNA probe that was generated from the clone hybridized with CHAT mRNA in several specific hypothalamic and brainstem areas in adult female macaque brain. Quantification of mRNA expression during various physiologic conditions will help establish the relevance of cholinergic neurons during ovulation and anovulation in primates. FUNDING NIH HD16631, HD18185 PUBLICATIONS Pau CY, Pau KYF, Spies HG. Putative estrogen receptor and a mRNA expression in male and female rhesus macaques. Mol Cell Endocrinol 146:59-68, 1998.

促性腺激素释放激素(GnRH)的排卵前释放 而女性和恒河猴体内的黄体生成素(LH)是依赖的 卵巢雌二醇-17分泌增强？(E)。这是E-Induced 促性腺激素释放激素/促黄体素释放激素峰伴有下丘脑和脑干的改变 被鉴定为神经肽Y(NPY)的细胞，去甲肾上腺素 (Ne)-、乙酰胆碱(Ach)-和γ-氨基丁酸 (GABA)神经元。我们的研究重点是E如何 影响与这些相关的转录-翻译事件 肽和递质系统以及这些中枢神经事件是如何 随着年龄的增长而变化，尤其是围绝经期 分泌物减少。E受体的两种异构体(ER？然后呢？)有 已经上报了。为了研究ER亚型的组织分布， 我们克隆并测序了恒河猴的两个cdna探针(126bp和291bp)。 猴子？？这些cdna片段类似于，但不完全相同。 人类急诊室-？序列。有没有人支持他--？和ER-？，我们 对几种外周和中枢神经内质网异构体进行了定量 逆转录-聚合酶链法检测男性和女性组织 反应(RT-PCR)。都是急诊室-？那急诊室呢？MRNA存在于 雄性和雌性生殖器官。只有急诊室-？表示为 肝脏、额叶皮质、尾状核、蓝斑和 小脑。在大脑的一些区域，即壳核，内部 包膜、海马体和下丘脑室旁，ER-？曾经是 在雌性中表达，但在雄性中不表达。在雌性猕猴身上 10-15岁儿童酪氨酸羟化酶(TH， 控制去甲肾上腺素合成的酶) 群体(A1、A2、A6)被E处理上调。然而， 在对围绝经期猴子(22岁)进行E治疗后， TH基因在A6区的表达水平受到抑制。 脑干。我们继续研究这个时代的相关性--和 脑干神经元中与E相关的TH基因反应下降。我们也 克隆了一个356bp的猴胆碱乙酰转移酶(ChAT)，该酶是 Ach合成的控制)对应于人类的 Chat N-1类型序列332到684。5=和3=引物序列 分别为TAAGATGGCAGCAAAACTCCC和ACCGATGACCAGCTGAGGTTT。 据我们所知，这段恒河猴的部分DNA序列 基因之前还没有被记录在案。MCHAT RNA探针是 从与ChAT mRNA杂交的克隆中产生几个特定的 成年雌性猕猴脑的下丘脑和脑干区。 不同生理状态下基因表达的定量研究 条件将有助于确定胆碱能神经元的相关性 在灵长类动物排卵和无排卵期间。资助NIH HD16631， HD18185出版物：Pau CY，Pau KYF，Spies HG。推定的雌激素 雄性和雌性恒河猴体内受体和α基因的表达。 莫尔细胞内分泌146：59-68,1998。