The long-range goal of our research is the application of multidisciplinary approaches to the elucidation on the molecular level of the steroid endocrine processes concerned with human development and reproduction and utilization of the results for the solution of biomedical and clinical problems. Our major concern is steroid hormone molecules, and the enzyme systems related to their biosynthesis. The investigations include the mechanism of estrogen and androgen biosynthesis, steroid hydroxylase and lyase reaction mechanisms, isolation, and characterization of estrogen synthetase and their multi-components, immunochemistry of aromatizing systems, identification of the courses of aromatase and other steroid biogenetic activities during fetal development in comparison with postnatal stages, the conformation of steroids in solid and solution, the competitive and noncompetitive inhibitors of hormone biosynthesis, steroid metabolism, and development of clinical assay methods. The methods involve synthesis of steroids with and without deuterium, tritium, carbon-13, carbon-14 and oxygen-18 labels at stereoselective and/or regiospecific positions, conformational analysis by neutron and X-ray crystallography and spectroscopy, chemical and biochemical distribution analysis of isotopes, incubations with various enzyme preparations, enzyme solubilization and purification, antibody production, and physicochemical and immunochemical technology.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD004945-15
Application #
3310343
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1976-12-01
Project End
1986-11-30
Budget Start
1984-12-01
Budget End
1985-11-30
Support Year
15
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Hauptman-Woodward Medical Research Institute
Department
Type
DUNS #
074025479
City
Buffalo
State
NY
Country
United States
Zip Code
14203
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Kao, Y C; Higashiyama, T; Yarborough, C et al. (1999) Functional characterization of 102-amino acid-deleted form of human aromatase (delta102-aromatase). Steroids 64:422-9
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Osawa, Y; Higashiyama, T; Toma, Y et al. (1997) Diverse function of aromatase and the N-terminal sequence deleted form. J Steroid Biochem Mol Biol 61:117-26
Albrecht, B A; Daels, P F (1997) Immunolocalization of 3 beta-hydroxysteroid dehydrogenase, cytochrome P450 17 alpha-hydroxylase/17,20-lyase and cytochrome P450 aromatase in the equine corpus luteum of dioestrus and early pregnancy. J Reprod Fertil 111:127-33
Ng, P C; Osawa, Y (1997) Preparation and characterization of the F (ab)2 fragments of an aromatase activity-suppressing monoclonal antibody. Steroids 62:776-81
Toma, Y; Higashiyama, T; Yarborough, C et al. (1996) Diverse functions of aromatase: O-deethylation of 7-ethoxycoumarin. Endocrinology 137:3791-6
Washida, N; Kitawaki, J; Higashiyama, T et al. (1996) Preparation of an activity-inhibiting monoclonal antibody against human placental aromatase cytochrome P450. Steroids 61:126-32

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