Cryptorchidism induced in normal rats by the relaxin-like factor inhibitor.
Cryptorchidism is a serious problem, which affects 2-5% of the male population. Failure of the testes to descend into the scrotal region impairs germ cell development and is associated with a greater incidence of testicular cancer. The relaxin-like factor (RLF or insulin-like-3) has been shown to be critically important for the timely descent of the testicles in mice. We have discovered that the signal initiation site of the RLF can be eliminated without measurable effects on hormone binding to its receptor and that the resulting RLF derivative is a competitive inhibitor of RLF called RLFi. RLFi administered to pregnant rats causes dose-dependent gonadal retention in the offspring. The ability to control the severity of the syndrome by altering the concentration of RLFi and the timing of administration enables us to study in detail the structural changes that are associated with the action of RLF during critical stages of development. Targeted inhibition of the physiological migration pattern of testicles by RLFi lets one dissect the physiological process such as to find a window for clinical application of RLF and to search for ancillary factors that might play a role during normal development.
Büllesbach
Erika E
EE
Department of, Biochemistry and Molecular Biology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, South Carolina 29425, USA.
Boockfor
Fredric R
FR
Fullbright
George
G
Schwabe
Christian
C
D000818:Animals; D001483:Base Sequence; D003456:Cryptorchidism / Q000196:embryology* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D047109:Fetal Development / Q000502:physiology; D017353:Gene Deletion; D005865:Gestational Age; D007328:Insulin / Q000235:genetics / Q000502:physiology; D008297:Male; D023421:Models, Animal; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics / Q000494:pharmacology*; D011247:Pregnancy; D011485:Protein Binding / Q000235:genetics; D011506:Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000235:genetics; D013737:Testis / Q000196:embryology*
D007328:Insulin; C084797:Leydig insulin-like protein; D010446:Peptide Fragments; D011506:Proteins; C528798:RLFi peptide, rat