RELAXIN-LIKE FACTOR IN MALE GONADAL DEVELOPMENT

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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.