RELAXIN-LIKE FACTOR IN MALE GONADAL DEVELOPMENT

男性性腺发育中的松弛素样因子

• 批准号: 6321710
• 负责人: christian none schwabe
• 金额: $ 28.2万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6321710
• 关键词: cell differentiation; cell migration; chemical synthesis; cryptorchidism; disease /disorder model; embryo /fetus chemotherapy; gene expression; hormone analog; hormone receptor; hormone regulation /control mechanism; hormone therapy; immunocytochemistry; laboratory rat; molecular cloning; morphometry; newborn animals; nonhuman therapy evaluation; peptide hormone analog; protein localization; protein structure function; relaxin; reproductive development; reproductive system disorder chemotherapy; testis; tissue /cell culture

DESCRIPTION: (Scanned from the applicant's abstract) In about 3.5 percent of newborn human males the gonads are undescended (chryptorchidism), a condition that leads to infertility and is associated with a high rate of testicular cancer. In the absence of any effective drugs, surgery is used widely to correct that condition. While surgery allows gonadal development to progress to fertility, it appears that the increased threat of testicular cancer is not reduced correspondingly. These are persuasive reasons to study the physiology and biochemistry of testicular development and explore the possibility of drug design to eliminate the defect and, with it, the propensity for testicular cancer formation. RLF (relaxin-like factor), which appears to be an absolute requirement for testicular development, is presently the best candidate for therapeutic intervention in the neonate. RLF can be detected in the sera of prepubertal children (0.3 ng/mL) but rises at puberty to 1.2 ng/mL in males only. Selective deletion of the RLF gene causes infertility in mice, and injection of our anti-RLF antibodies into pregnant rats, 5 days pre-partum, caused retention of testicles in the body cavity at 20 days of age when all the control animals had totally descended gonads. There can be no doubt that RLF is a necessary component of the regulatory chain of events for gonadal development and that absence of or a defect in the RLF gene or the RLF receptor gene may be the cause of the developmental disturbance in segments of our population. Our work will highlight the role RLF is playing in these processes and will significantly improve the prospects for a drug to treat cryptorchidism. We intend to use specially designed synthetic RLF derivatives and anti-RLF antibodies to study the process of gonadal development and to examine the prospects of substitution therapy. RLF is a small molecule of about 6,300 Dalton, which will pentrate the intestinal wall of the neonate and enter the bloodstream so that gonadal complications detected at birth could be treated immediately by dietary supplement.

描述：(从申请人的摘要中扫描)约3.5% 新生的人类男性性腺未下降(隐睾症)，一种情况 这会导致不育症，并与高睾丸发生率有关。 癌症。在没有任何有效药物的情况下，外科手术被广泛用于 纠正这一状况。虽然手术可以使性腺发育进展到 生育力，似乎增加的睾丸癌威胁并不是 相应地减少了。这些都是研究生理学的有说服力的理由 和生物化学对睾丸发育的影响，并探索药物的可能性 消除缺陷的设计，以及随之而来的睾丸倾向 癌症的形成。 RLF(松弛素样因子)，这似乎是 睾丸发育，是目前最好的治疗方案 对新生儿的干预。在青春期前儿童血清中可检测到RLF 儿童(0.3 ng/毫升)，但青春期仅男性上升至1.2 ng/毫升。有选择性的 RLF基因缺失导致小鼠不育，注射OUR 抗RLF抗体注入孕鼠，产前5天，引起胎盘滞留 20日龄时体腔内的睾丸，而所有对照动物 性腺完全下降。毫无疑问，RLF是一种必要的 性腺发育调节链的组成部分，以及 RLF基因或RLF受体基因缺失或缺陷可能是 这是我国部分人口出现发育障碍的原因。我们的工作 将强调RLF在这些进程中发挥的作用，并将 显著改善治疗隐睾症的药物的前景。 我们打算使用特别设计的合成RLF衍生物和抗RLF 抗体用于研究性腺发育过程和检测 替代疗法的发展前景。RLF是一个小分子，大约有6300个 多尔顿，它会使新生儿的肠壁五分五裂，进入 血流，以便可以治疗出生时发现的性腺并发症 立即服用膳食补充剂。