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BOR - Papers in Press, published online ahead of print October 30, 2002.
Biol Reprod 2002, 10.1095/biolreprod.102.003483
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Submitted January 11, 2002
Returned for revision February 8, 2002
Accepted October 11, 2002

Ovary


Action of Gonadotropin-Releasing Hormone II on Baboon Ovary

Theresa M. Siler-Khodr 1*, Marcia Grayson 2, Carlton A. Eddy 3
1 The University of Texas
2 University of Texas Health Science Center at San Antonio
3 The University of Texas Health Science Center at San Antonio

* To whom correspondence should be addressed. E-mail: silerkhodr{at}uthscsa.edu.

Abstract

The content, binding affinity and bioactivity of chicken II GnRH (GnRH II) and a stable analog of GnRH II (GnRH II analog) in the baboon ovary were studied. While mammalian GnRH is rapidly degraded by baboon ovarian extracts, we have designed a GnRH II analog, which is stable to ovarian enzymatic degradation. This analog of GnRH II was found to bind to the ovarian membranes with high affinity (41 ± 3 nM), having 20-fold the affinity of Buserelin, a mammalian GnRH analog. The bioactivity of GnRH II and this GnRH II analog on the regulation of ovarian progesterone release was compared to that for Buserelin using a baboon granulosa cell culture system. Both GnRH II and GnRH II analog effected a 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 analog. After 24 hours in culture this GnRH II analog effected a 59 ± 5% inhibition of progesterone using a concentration as low as1 nM. A maximal inhibition of 75 ± 1% was attained with 10 nM GnRH II analog. 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 forty-eight hours in culture. These studies demonstrate the presence of high enzymatic activity for the degradation of mammalian GnRH in the ovary, while this GnRH II analog was stable. The presence of high affinity binding sites for this GnRH II analog was found. In addition, we have shown that GnRH II and this GnRH II analog can regulate progesterone production from baboon granulosa cells. These findings have led us to propose that GnRH II is a potent regulator of ovarian function.



Key words: Ovary • Gonadotropin-releasing hormone • Gonadotropin-releasing hormone receptor • Progesterone


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