Although many events in the mammalian uterus are steroid hormone dependent, little is known about the cellular mechanisms through which estradiol and progesterone direct specific uterine functions. The proposed research will determine if certain actions of steroid hormones on different uterine cell types could be mediated by transforming growth factor beta (TGFB). Since it is not yet known if TGFB is regulated by steroid hormones in the uterus, synthesis of this protein will be examined during two important uterine functions which are directed by distinct hormonal milieux; receptivity to embryo attachment and cell death. TGFB transcription and synthesis will be examined in separated luminal epithelial and stromal cells from the rat uterus under hormonal conditions which give rise to each of these functions. Uterine receptivity will be induced in ovariectomized rats by a series of progesterone and estradiol injections which mimic the hormonal conditions of early pregnancy. Cell death will be induced by ovariectomy. TGFB transcription will be measured using northern and RNA slot-blot hybridization analyses of cytoplasmic RNA as well as transcription and nuclear run-off assays of newly transcribed RNA in cell nuclei. Synthesis of TGFB will be analyzed by gel-electrophoresis and immunoblotting of uterine cell proteins. The results of these experiments should demonstrate whether a change in TGFB synthesis is associated either with receptivity to embryo attachment or with cell death, if TGFB synthesis is regulated by steroid hormones in specific uterine cell types, and whether this regulation is transcriptional, posttranscriptional, or translational. If a role for TGFB in establishing receptivity for embryo implantation in the rat is indicated by this research, a firm precedent would be established for future investigations to determine if TGFB serves the same function in other mammals and if it is involved in human infertility.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Small Research Grants (R03)
Project #
1R03HD028122-01
Application #
3426730
Study Section
Special Emphasis Panel (SRC (09))
Project Start
1991-05-01
Project End
1993-04-30
Budget Start
1991-05-01
Budget End
1992-04-30
Support Year
1
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Baylor College of Medicine
Department
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030