PARENT SESSION
PLATFORM SESSION 2: REGULATION OF OVARIAN FOLLICULAR EXPRESSION
Chair: Adashi, Eli¹, ¹
Co-chair: Salvador, Lisa¹, ¹
Harborside C
4:30 PM-6:30 PM

(7) DISCOVERY OF AN OVARY-SELECTIVE GENE THAT ENCODES A PROTEIN WITH A UNIQUE TRYPSIN-LIKE PROTEASE DOMAIN.

Hennebold, Jon¹, Stouffer, Richard^1,2, Macfarlane, Jane³, Adashi, Eli³, ¹ Division of Reproductive Sciences, Beaverton, OR² Department of Physiology & Pharmacology, Portland, OR³ Department of Obstetrics and Gynecology, Salt Lake City, UT

ABSTRACT- Through the course of identifying novel genes that are selectively expressed in the ovary, one gene was chosen for further investigation based on its unique pattern of expression (increased expression during the periovulatory and luteal phase of a stimulated estrous cycle). The determination of the full-length cDNA sequence of this gene led to the identification of an open reading frame capable of encoding a protein that possesses a trypsin-like protease domain. As this putative protease is expressed selectively within the mouse ovary, it was subsequently termed Ovary-Selective Protease (OSP). Our goal, therefore, was to characterize the molecular attributes of this putative protease as related to ovarian physiology. The cellular site of expression for OSP, as determined by in situ hybridization, was localized to the theca cells surrounding follicles at the earliest stages of development (primary, secondary, and early antral), but expression also became evident in the granulosa cells of preovulatory follicles following the administration of gonadotropins. The highest level of OSP expression was observed in the cells comprising the corpus luteum (CL). Recent analysis of the human and mouse databases has led to the identification of additional putative trypsin-like proteins. Via an RT-PCR approach using the human sequence for PCR primer design, a macaque homolog was identified and analyzed with respect to its expression in the CL at different stages of development. Real-time PCR demonstrated that the monkey OSP homolog was expressed at a 4.6-fold higher level in the CL at the late-point of the luteal phase (day 14 post-LH surge; p<.05) relative to CL isolated from the beginning (day 3 post-LH surge) or end (day 18 post-LH surge) of the luteal phase. Phylogenetic analysis suggests that these molecules comprise a unique, previously unidentified family of proteases. These findings support the hypothesis that the putative OSP (and perhaps related family members) plays a critical role in the remodeling and cellular reorganization required for follicular growth, rupture of a mature follicle, and development/regression of a functional CL. Supported by NIH Grants HD30288, HD37845, HD20869, and U54 Center Grant HD18185.

KEY WORDS: protease, corpus luteum, ovary