NEUROTENSIN AND FEMALE-SPECIFIC LH SECRETION

神经降压素和女性特异性 LH 分泌

• 批准号: 3229098
• 负责人: SUSAN E LEEMAN
• 金额: $ 22.11万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-12-01 至 1996-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3229098
• 关键词: animal puberty; developmental genetics; estrogen receptors; estrogens; estrus; female; gender difference; gene expression; gonadotropin releasing factor; hormone regulation /control mechanism; hypothalamic pituitary axis; in situ hybridization; laboratory rat; luteinizing hormone; male; male castration; messenger RNA; neuroendocrine system; neuropeptide receptor; neurotensin; newborn animals; ovariectomy; pituitary gonadal axis; preoptic areas; radioimmunoassay; receptor expression; secretion; sex differentiation; testosterone

Neurons that synthesize the peptide neurotensin (NT) are particularly abundant in the preoptic area and may play an important role in regulating neuroendocrine function, many aspects of which are sexually differentiated. This proposal seeks to clarify the relationship between female-specific, estrogen-dependent expression of the neurotensin/neuromedin N (NT/N) gene in the rat preoptic area and female-specific regulation of luteinizing hormone (LH) secretion. A major objective of this proposal is to determine the extent to which estrogen can act directly on NT neurons in the preoptic area. To that end, in situ hybridization histochemistry will be used to determine the detailed regional distribution of neurons that express both NT/N mRNA and estrogen receptor mRNA in the male preoptic area and female preoptic area. A second major objective of this proposal is to determine the extent to which NT can act directly on neurons that synthesize gonadotropin-releasing hormone (GnRH). To that end, in situ hybridization histochemistry will be used to determine the detailed regional distribution of neurons that express both GnRH mRNA and NT receptor mRNA in the basal forebrain of the male and female. In addition, the effect of estrogen on the abundance of NT receptor mRNA in GnRH neurons will be determined. A third major objective of this proposal is to investigate the development of female-specific NT/N gene expression in the preoptic area. Developmental parameters to be investigated include: a) the age at which the distribution of NT/N mRNA in the preoptic area becomes sexually differentiated, b) the extent to which sexually differentiated expression of NT/N mRNA in the adult preoptic area is determined by neonatal androgen levels, and c) the age at which estrogen is able to alter the abundance of NT/N mRNA in the female preoptic area. The results of these developmental studies will help to clarify the role of NT neurons in the development of female-specific regulation of LH secretion. Identifying neuro- transmitters that regulate GnRH neurons will further our understanding of neural regulation of the menstrual cycle, may provide insight into its pathology, and may point the way toward novel therapeutic approaches.

合成肽神经降压素（NT）的神经元特别 丰富地存在于视前区，可能在 调节神经内分泌功能，其中许多方面与性有关 差异化。 该提案旨在澄清两者之间的关系 女性特异性、雌激素依赖性表达 大鼠视前区的神经降压素/神经调节蛋白 N (NT/N) 基因 女性特有的黄体生成素 (LH) 分泌调节。 一个 该提案的主要目标是确定 雌激素可以直接作用于视前区的 NT 神经元。 对此 最后，将使用原位杂交组织化学来确定 表达 NT/N mRNA 的神经元的详细区域分布 男性视前区和女性视前区的雌激素受体 mRNA 区域。 该提案的第二个主要目标是确定 NT 可以直接作用于合成神经元的程度 促性腺激素释放激素（GnRH）。 为此，现场 杂交组织化学将用于确定详细的 同时表达 GnRH mRNA 和 NT 的神经元的区域分布 男性和女性基底前脑中的受体 mRNA。 在 此外，雌激素对 NT 受体 mRNA 丰度的影响 GnRH 神经元将被确定。 本次活动的第三个主要目标 提案是研究女性特有的 NT/N 基因的发育 表达于视前区。 发育参数为 调查的内容包括： a) NT/N mRNA 分布的年龄 在视前区变得性别分化，b）程度 成人中 NT/N mRNA 的表达存在性别差异 视前区由新生儿雄激素水平决定，c) 年龄 雌激素能够改变 NT/N mRNA 的丰度 女性视前区。 这些发展研究的结果将 有助于阐明 NT 神经元在发育中的作用 LH 分泌的女性特异性调节。 识别神经- 调节 GnRH 神经元的递质将进一步加深我们对 月经周期的神经调节，可能有助于深入了解其 病理学，并可能为新的治疗方法指明道路。