REGULATION OF LEYDIG CELL-SECRETED POLYPEPTIDES

间质细胞分泌的多肽的调节

• 批准号: 2197270
• 负责人: PATRICIA L. MORRIS
• 金额: $ 19.7万
• 依托单位: POPULATION COUNCIL
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-09-30 至 1997-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2197270
• 关键词: Leydig cells; adenylate cyclase; autocrine; cell population study; cytokine; gene expression; growth factor; growth factor receptors; high performance liquid chromatography; hormone receptor; hormone regulation /control mechanism; immature animal; immunocytochemistry; in situ hybridization; laboratory mouse; laboratory rabbit; laboratory rat; luteinizing hormone; messenger RNA; molecular cloning; paracrine; pituitary hormones; polymerase chain reaction; prolactin releasing /inhibiting factor; protein sequence; radiotracer; spermatogenesis; testis; tissue /cell culture; transforming growth factors; western blottings

Ultimately the primary function of all somatic cells in the testis is to ensure a microenvironment that provides adequate androgen and nutritive support for spermatogenesis and confers immunologic tolerance for the mitotic spermatogonia located outside the blood-testis barrier. It is well known that the pituitary hormones LH and PRL affect androgen secretion by Leydig cells. What is less well understood is the identity and function of the local peptidergic factors that make up the non- steroidal microenvironment of the interstitium. LACAF is an interstitial cell protein stimulated by HCG and growth factor but inhibited by prolactin. LACAF activates adenylyl cyclase in Leydig cells but this activation is not functionally directed towards steroidogenesis. Such differential regulation is by known Leydig cell trophic factors suggests that LACAF is an autocrine regulatory factor. This protein shows some sequence homology with the testicular protein of the VIP family of peptides that shares this capacity to activate cyclase without concomitant effects on steroidogenesis. We will study the function and regulation of these two proteins in parallel. Prolactin preferentially enhances the secretion of two other interstitial proteins, one of which is a known immunomodulator, suggesting the prolactin affects testicular immune elements. The second protein, PIL, may be a member of the transforming growth factor Beta family of peptides. The physiological significance of this regulated pattern of interstitial proteins is presently unknown. Our proposed studies will focus on the unique features of the regulation of LACAF, PIL and complement components by prolactin. The ability to determine the various forms of the prolactin receptor MRNAS affords the opportunity to determine the cell-specificity of these prolactin-induced changes in interstitial protein secretion. LACAF and PIL proteins will be further characterized. Cloned CDNAS for these interstitial proteins will be isolated and their structure characterized. Moreover, specific probes will be generated for use in determining both physiological and aberrant expression of these proteins in vivo and in vitro studies. Regulation of these interstitial proteins will be studied by analysis of their MRNA levels as a function of endocrine status using hybridization in situ and immunohistochemistry. The mechanism(s) of action of these peptides will be investigated by assessment of their effects on both seminiferous tubule and interstitial cell function. This research plan will lead to new, significant data on the mediators of intratesticular signalling and their physiological relevance in the testis.

最终，睾丸中所有体细胞的主要功能是 确保提供足够的雄激素和营养的微环境 支持精子发生并赋予免疫耐受性 有丝分裂的精子症位于血端屏障外。这是 众所周知，垂体激素LH和PRL会影响雄激素 Leydig细胞的分泌。不太了解的是身份 以及构成非 - 间质的类固醇微环境。 LACAF是一种间隙细胞蛋白，由HCG刺激和生长刺激 因子，但被催乳素抑制。 LACAF激活腺苷酸环化酶 Leydig单元格，但这种激活并非功能性地针对 类固醇生成。这种差异调节是通过已知的leydig细胞 营养因素表明LACAF是自分泌调节因素。 该蛋白显示了与睾丸蛋白的某些序列同源性 具有这种激活环化酶能力的肽家族的VIP家族 没有对类固醇生成的影响。我们将研究 并行的这两种蛋白质的功能和调节。 催乳素优先增强了另外两个的分泌 间质蛋白，其中一种是已知的免疫调节剂， 表明催乳素会影响睾丸免疫元件。第二个 蛋白质，PIL可能是转化生长因子β的成员 肽家族。该调节的生理意义 间质蛋白的模式目前未知。我们提出的 研究将重点介绍LACAF监管的独特特征， PIL和催乳素的补充成分。确定 各种形式的催乳素受体mRNA提供了机会 确定这些催乳素诱导的变化的细胞特异性 间质蛋白分泌。 LACAF和PIL蛋白将进一步表征。克隆的cdnas 这些间质蛋白将被隔离，它们的结构 特征。此外，将生成特定的探针以供在 确定这些蛋白质的生理和异常表达 体内和体外研究。这些间隙蛋白的调节 将通过分析其mRNA水平作为函数来研究 使用杂交原位和免疫组织化学的内分泌状态。 这些肽的作用机制将通过 评估其对生精小管和间质的影响 细胞功能。该研究计划将导致有关的新的重要数据 肠内信号传导及其生理的介体 与睾丸相关。