title: Biochemistry, molecular biology and cell biology of gonadotropin-releasing hormone antagonists.
abstract: OBJECTIVE
  Gonadotropin-releasing hormone (GnRH) receptors are not only detected in the central nervous system but also in tissues such as ovary, endometrium, breast, gastrointestinal system, placenta and malignant tumors of ovary and breast. The direct role of GnRH-antagonists in ovarian function, implantation, cancer pathogenesis and treatment is under extensive investigation. This study reviews the biochemistry and molecular and cellular biology of GnRH-antagonists as well as GnRH types and their receptors.
  
  
  RESULTS
  The best clinical evidence with GnRH-antagonists has accumulated in controlled ovarian hyperstimulation protocols for prevention of premature luteinizing hormone surge (cetrorelix, ganirelix) and in the treatment of advanced-stage prostate cancer (abarelix and degarelix). GnRH-GnRH receptor pathways may have a role in the embryo implantation. The controversy still exists whether GnRH antagonist protocols result in slightly decreased clinical pregnancy rates compared with the GnRH agonist protocols. GnRH-antagonists could be used in the near future to treat some cancer types that express GnRH receptors.
  
  
  CONCLUSIONS
  GnRH-antagonists have various clinical applications in gynecology, reproductive medicine, urology and oncology. The emergence of well tolerated, orally active GnRH-antagonists may provide an alternative to long-term injections and is likely to have a major impact on the utility of GnRH analogues in the treatment of human diseases.
authors.affiliation: Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9032, USA. Orhan.Bukulmez@UTSouthwestern.edu
authors.forename: Orkun
authors.initials: O
authors.lastname: Tan
authors.forename: Orhan
authors.initials: O
authors.lastname: Bukulmez
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy*; D010064:Embryo Implantation / Q000187:drug effects; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists / Q000037:antagonists & inhibitors*; D006727:Hormone Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D010062:Ovulation Induction; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D011966:Receptors, LHRH / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
chemical_list: D006727:Hormone Antagonists; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone