REGULATORY MECHANISMS OF OVARIAN PROGESTERONE RECEPTORS

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Dr. Ok-Kyong Park-Sarge was appointed an Assistant Professor in the Department of Physiology in July 1993. She has demonstrated outstanding competence as a biomedical researcher during the last 18 months. She was awarded an NIH FIRST AWARD (R29) and has applied for pilot funds from both the Markey Cancer Center and the Center on Aging at the University of Kentucky. She is a member of the NIH-funded Reproductive Sciences Training Program and actively interacts with members of the markey Cancer Center and the Center on Aging. At the present time, teaching and service activities comprise about 50% of her effort. With support from an RCDA, Dr. Park- Sarge would be relieved of formal teaching and service activities and would be able to concentrate on the conduct or supervision of research including supervision of graduate students or postdoctoral fellows. A significant reduction in her teaching and service activities would also allow Dr. Park- Sarge to obtain research training in several techniques important for future studies. Dr Park-Sarge's research has focused on the regulatory mechanisms of the progesterone receptor gene in tahe ovary. The observation she made during her postdoctoral training period, that the ovary transiently expresses the progesterone receptor gene in granulosa cells of preovulatory follicles during the period critical for ovulatory processes, clearly suggests that the ovary is a target of autocrine or paracrine action of progesterone. She has further determined that the primary mechanism regulating the progesterone receptor gene in this tissue is through activation of membrane receptors for gonadotropins. Thus, these findings reveal a striking difference between regulation of the progesterone receptor gene int he ovary compared to any other progesterone receptor-containing tissue. Her long-term goal is to better understand athe role of ovarian progesterone receptors in the regulation of fertility in normal and dysfunctional reproductive processes. Her immediate goal is to determine the molecular mechanisms for gonadotropin-stimulated progesterone receptor transcription in the ovary. During the award period, she will examine the cellular and molecular mechanisms of progesterone receptor gene transcription. She will determine the role of protein kinase A and C in gonadotropin-stimulated progesterone receptor expression in granulosa cells and define cis-regulatory sequences that mediate gonadotropin-induced PR expression. In addition, she will determine the basis of the lack of estrogen-stimulated activation of this gene. Moreover, she will apply athe information on PR expression in young female rats to aging female rats to examine whether age-related alterations of PR expression may explain some of the observed changes that occur during reproductive aging. Her interaction with members of the reproductive biology group, the Markey Cancer Center, and the Center on Aging at the University of Kentucky will facilitate her growth as a leader within the scientific community. A strong commitment to Dr. Park-Sarge from the University of Kentucky together with the RCDA will make a critical difference in Dr. Park-Sarge's future status as leader within the scientific community.