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Action of Chicken II GnRH on the Human Placenta¹

Department of Obstetrics and Gynecology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229

Address correspondence and requests for reprints to: Theresa M. Siler-Khodr, Ph.D., Professor, Department Obstetrics and Gynecology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, Room 416E, San Antonio, Texas 78229. E-mail: Silerkhodr{at}UTHSCSA.edu

The stability, receptor binding, bioactivity, and production of chicken II GnRH and its analogs in the human placenta were studied. Both chicken II and mammalian GnRH are rapidly degraded by placental enzymes, yet the chicken II isoform is six times more stable. Analogs of chicken II GnRH were synthesized, and their stability in the presence of placental enzymes was tested. The D-Arg(6)-chicken II GnRH-aza-Gly(10)-NH₂ analog was found to be resistant to enzymatic degradation. The placental receptor binding activity of the chicken II GnRH analogs and chicken II GnRH was compared with that of mammalian GnRH and its analogs. Because D-Arg(6)-chicken II GnRH-aza-Gly(10)-NH₂ had the highest affinity for the placental receptor and was stable in placental extracts, the bioactivity of this analog on the regulation of placental human CG (hCG) release was compared with that for mammalian and chicken II GnRH using a human term placental explant culture system. This chicken II GnRH analog effected a stimulation of hCG at the lowest concentration studied (250 nM). With extended exposure and/or higher concentrations of this chicken II GnRH analog, the release of hCG from human placental explants was inhibited. Using a placental explant perifusion system and a highly specific RIA for chicken II GnRH, the pulsatile release of chicken II GnRH from the early human placenta was demonstrated.

These studies are the first to demonstrate bioactivity of a second form of GnRH in a human tissue and to identify the pulsatile release of chicken II GnRH from a human tissue. These data led us to propose that chicken II GnRH and its synthetic analogs may be potent ligands for hormone regulation during pregnancy.

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