The human placenta has been shown to be a source of large quantities of prostanoids. Among these prostanoids, are prostaglandins (PGs), thromboxane and prostacyclin, each of which have been shown to play an important role in implantation, normal fetal development, as well as the initiation and progress of labor. However, little is known about the control of placental prostanoid production. In recent studies we have demonstrated that gonadotropin releasing hormone (GnRH), and chorionic GnRHase, a newly isolated glycoprotein of the placenta which degrades GnRH have potent prostaglandin stimulating activity. Herein, we propose to study the basal release of prostaglandins, thromboxine and prostacyclin from human term placenta in vitro. The release of these prostanoids will be determined by HPLC analysis and RIA of the medium from perifused human term placentas. Critical steps in their production will then be determined using exogenous substrate or specific enzyme inhibitors. The role of endogenous and exogenous GnRH and chorionic GnRHase on placental prostanoid release will also be studied using antiserum to or inhibitors of these factors. Also, the effect of exogenous GnRH or chorionic GnRHase in the incubation medium will be determined. In addition, the role of progesterone and estrogens in modulating placental prostanoid production as well as these steroids effect on the GnRH and chorionic GnRHase stimulation of prostaglandins, thromboxines and prostacyclin will be examined. These studies should provide us with basic infomation on placental prostanoid production and their control by GnRH chorionic GnRHase as well as defining the modulatory role of progesterone and estrogen in these hormone productions. These data may enable us to devise protocols to modify prostanoid production. Due to the very important role of prostanoids in implantation, in placental and fetal blood flow and in the initiaion and progress of labor, these studies may provide needed information which may be able to better control the outcome of abnormal pregnancies by appropriately affecting prostanoid production.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
1R01HD021708-01A1
Application #
3320737
Study Section
Human Embryology and Development Subcommittee 2 (HED)
Project Start
1988-09-01
Project End
1991-08-31
Budget Start
1988-09-01
Budget End
1989-08-31
Support Year
1
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Texas Health Science Center San Antonio
Department
Type
Schools of Medicine
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
Siler-Khodr, T M; Kang, I S; Koong, M K et al. (1997) The effect of dexamethasone on CRH and prostanoid production from human term placenta. Prostaglandins 54:639-53
Siler-Khodr, T M; Kang, I S; Koong, M K (1996) Dose-related action of estradiol on placental prostanoid prediction. Prostaglandins 51:387-401
Siler-Khodr, T M; Forman, J; Sorem, K A (1995) Dose-related effect of IGF-I on placental prostanoid release. Prostaglandins 49:1-14
Kang, I S; Siler-Khodr, T M (1993) Effect of exogenous arachidonic acid and enzyme inhibitors on placental prostanoid production. Placenta 14:341-53
Siler-Khodr, T M; Forman, J (1993) Effect of IGF-1 on placental prostanoid production. Prostaglandins 46:361-70
Kang, I S; Siler-Khodr, T M (1992) Chorionic peptidase inactivates GnRH as a post-proline peptidase. Placenta 13:81-7
Kang, I S; Koong, M K; Forman, J et al. (1991) Dose-related action of gonadotropin-releasing hormone on basal prostanoid production from the human term placenta. Am J Obstet Gynecol 165:1771-6
Siler-Khodr, T M; Kang, I A; Khodr, G S (1991) Effects of chorionic GNRH on intrauterine tissues and pregnancy. Placenta 12:91-103
Siler-Khodr, T M; Kang, I S; Jones, M A et al. (1989) Characterization and purification of a placental protein that inactivates GnRH, TRH and angiotensin II. Placenta 10:283-96