Action of gonadotropin-releasing hormone II on the baboon ovary.
The content, binding affinity, and bioactivity of chicken II GnRH (GnRH II) and a stable analogue of GnRH II (GnRH II analogue) in the baboon ovary were studied. Although mammalian GnRH is rapidly degraded by baboon ovarian extracts, we designed a GnRH II analogue that is stable to ovarian enzymatic degradation. This analogue binds to the ovarian membranes with high affinity (41 +/- 3 nM), having 20-fold the affinity of a potent mammalian GnRH analogue. The bioactivity of GnRH II and this GnRH II analogue on the regulation of ovarian progesterone release was compared with that for a potent mammalian GnRH analogue using a baboon granulosa cell culture system. Both GnRH II and GnRH II analogue produced significant inhibition of progesterone release from the granulosa cells (P < 0.03 and P < 0.005, respectively), with a greater reduction observed using the GnRH II analogue. After 24 h in culture, this GnRH II analogue produced a 59% +/- 5% inhibition of progesterone with a concentration as low as 1 nM. Maximal inhibition of 75% +/- 1% was attained with 10 nM GnRH II analogue. The endogenous GnRH II content in the baboon ovary was 5-14 pmoles/g protein. The release of endogenous GnRH II from granulosa cells was observed throughout the 48 h in culture. These studies demonstrated the presence of high enzymatic activity for the degradation of mammalian GnRH in the ovary, whereas this GnRH II analogue was stable. High-affinity binding sites for this GnRH II analogue were also found. GnRH II and this GnRH II analogue can regulate progesterone production from baboon granulosa cells, suggesting that GnRH II is a potent regulator of ovarian function.
Siler-Khodr
Theresa M
TM
Department of Obstetrics & Gynecology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, USA. silerkhodr@uthcsa.edu
Grayson
Marcia
M
Eddy
Carlton A
CA
D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002064:Buserelin / Q000378:metabolism / Q000494:pharmacology; D002478:Cells, Cultured; D002645:Chickens; D004305:Dose-Response Relationship, Drug; D005260:Female; D005300:Fertility Agents, Female / Q000378:metabolism / Q000494:pharmacology; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism / Q000502:physiology*; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D010053:Ovary / Q000737:chemistry / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D010215:Papio; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism; D011374:Progesterone / Q000037:antagonists & inhibitors / Q000378:metabolism; D014020:Tissue Extracts / Q000378:metabolism
D005300:Fertility Agents, Female; D014020:Tissue Extracts; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D007986:Luteinizing Hormone; D002064:Buserelin