REPRODUCTIVE SIGNALLING IN BRAINSTEM

脑干中的生殖信号传导

• 批准号: 6247238
• 负责人: HAROLD G SPIES
• 金额: $ 4.86万
• 依托单位: OREGON REGIONAL PRIMATE RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-05-01 至 1998-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6247238
• 关键词: Mammalia; Primates; biological products; endocrine gland /system; hormones; nervous system; reproductive system; women's health

Inadequate activities in select brain neurons can cause many diseases, including infertility. For example, reproductive incompetence is a frequent symptom in patients with over-eating and drug problems, both of which can be addictive. The anatomical and physiological associations between obesity, drug addiction and infertility are unknown, although three neurochemicals, i.e., neuropeptide Y (NPY), norepinephrine transporter (NET) and norepinephrine (NE), are likely involved. Each of the three brain substances can influence the secretion of gonadotropin-releasing hormone (GnRH, a deca-peptide that is a key regulator of reproduction). NPY and NE alter eating behavior and NET and NE are involved in addiction. We hypothesize that integration of the three neurochemicals occurs in the brainstem and we utilized the rabbit as an initial model (before primate studies) to identify the distribution of brainstem cells containing NPY, NET and tyrosine hydroxylase (TH, the rate-limiting enzyme for NE synthesis) mRNAs by in situ hybridization. Specific rabbit NET and TH cDNA fragments were cloned by reverse transcription-polymerase chain reaction and their nucleotide sequences were determined. These two cDNA (as well as a human NPY cDNA) fragments were used as probes for hybridization with respective mRNAs through the entire length of rabbit brainstems that were sectioned at 20 fm thickness. Serial sections were also stained for the presence of dopamine- -hydroxylase (D H, a protein enzyme specific for NE synthesis) by immunocytochemistry to mark brainstem NE cells. The data suggest that while NET and TH mRNAs were located in all D H-positive areas including the locus coeruleus (LC, an area that consists of predominantly NE cells), NPY mRNA was not observed in LC cells. However, the lateral tegmentum and the nucleus of the solitary tract contained cells that expressed all three genes. These results provide an anatomical basis for potential NPY, NET and NE integration of peripheral and central signals that may modulate eating behavior, drug addiction and reproductive performance.

某些脑神经元的活动不足会导致许多 疾病，包括不孕症。 例如，生殖 功能不全是暴饮暴食患者的常见症状， 毒品问题，这两种都可以上瘾。 的解剖学和 肥胖、药物成瘾和 不孕症是未知的，虽然三种神经化学物质，即， 神经肽Y（NPY）、去甲肾上腺素转运蛋白（NET）和 去甲肾上腺素（NE）可能参与其中。 三个大脑中的每个 物质可以影响促性腺激素释放激素的分泌， 激素（GnRH，一种十肽， 生殖）。 NPY和NE改变进食行为，而NET和NE是 参与成瘾。 我们假设这三者的结合 神经化学物质发生在脑干，我们利用兔子作为 用于确定分布的初始模型（在灵长类动物研究之前） 含有NPY、NET和酪氨酸羟化酶（TH， NE合成限速酶）mRNA 杂交方法 克隆了兔NET和TH的特异性cDNA片段 通过逆转录聚合酶链反应， 测定核苷酸序列。 这两个cDNA（以及一个 人NPY cDNA）片段用作探针，与 在兔脑干的整个长度上， 切片厚度为20 μ m。 连续切片也被染色 多巴胺-羟化酶（D-H，一种蛋白酶 特异于NE合成）标记脑干NE 细胞 数据表明，虽然NET和TH mRNA位于 所有DH阳性区域，包括蓝斑（LC， 在LC中未观察到NPY mRNA的表达 细胞 然而，外侧被盖和孤束核 道含有表达所有三种基因的细胞。 这些结果 为潜在的NPY、NET和NE整合提供解剖学基础 调节进食行为的外周和中枢信号， 药物成瘾和生殖能力。