RELAXIN-LIKE FACTOR IN MALE GONADAL DEVELOPMENT

描述：（从申请人的摘要中扫描）约占 3.5% 新生儿男性的性腺未下降（隐睾），一种病症 这会导致不孕并与高睾丸率相关 癌症。在缺乏有效药物的情况下，手术治疗被广泛采用 更正该条件。虽然手术可以使性腺发育进展到 生育能力，睾丸癌威胁的增加似乎并没有增加 相应减少。这些是研究生理学的有说服力的理由 睾丸发育的生物化学和探索药物的可能性 旨在消除缺陷以及随之而来的睾丸倾向的设计 癌症的形成。 RLF（类松弛因子），这似乎是 睾丸发育，是目前治疗的最佳候选者 对新生儿的干预。 RLF可在青春期前的血清中检测到 儿童（0.3 ng/mL），但在青春期仅在男性中升至 1.2 ng/mL。选择性 RLF 基因的缺失会导致小鼠不育，注射我们的 产前 5 天将抗 RLF 抗体注入怀孕大鼠体内，导致保留 20日龄时，所有对照动物的睾丸都在体腔内 性腺完全下降。毫无疑问，RLF 是必要的 性腺发育事件调控链的组成部分 RLF基因或RLF受体基因的缺失或缺陷可能是 我们部分人口发育障碍的原因。我们的工作 将强调 RLF 在这些过程中发挥的作用，并将 显着改善治疗隐睾症药物的前景。 我们打算使用专门设计的合成RLF衍生物和抗RLF 抗体来研究性腺发育过程并检查 替代疗法的前景。 RLF是约6,300个小分子 道尔顿，它会穿透新生儿的肠壁并进入 血液循环，以便治疗出生时检测到的性腺并发症 立即通过膳食补充剂。

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.