REPRODUCTIVE SIGNALLING IN BRAINSTEM

特定大脑神经元的活动不足可能会导致许多 疾病，包括不孕症。 例如，生殖 无力是暴饮暴食患者的常见症状 毒品问题，两者都可能使人上瘾。 解剖学和 肥胖、药物成瘾和肥胖之间的生理联系 尽管存在三种神经化学物质，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。 三个大脑中的每一个 物质可以影响促性腺激素释放的分泌 激素（GnRH，一种十肽，是 繁殖）。 NPY 和 NE 改变饮食行为，NET 和 NE 改变饮食行为 涉及成瘾。 我们假设三者的整合 神经化学物质发生在脑干中，我们利用兔子作为 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合成的限速酶）mRNA通过原位 杂交。 克隆了特定的兔 NET 和 TH cDNA 片段 逆转录聚合酶链式反应及其 确定了核苷酸序列。 这两个 cDNA（以及 人 NPY cDNA) 片段用作杂交探针 各个 mRNA 穿过兔脑干的整个长度 以 20 fm 厚度进行切片。 系列切片也被染色 检测多巴胺-β羟化酶（D H，一种蛋白质酶）的存在 特异性针对 NE 合成）通过免疫细胞化学标记脑干 NE 细胞。 数据表明，虽然 NET 和 TH mRNA 位于 所有 D H 阳性区域，包括蓝斑（LC，该区域 主要由 NE 细胞组成），在 LC 中未观察到 NPY mRNA 细胞。 然而，外侧被盖和孤立核 束包含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 可能调节饮食行为的外周和中枢信号， 吸毒成瘾和生殖能力。

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.