# HUMAN DEVELOPMENT AND ESTROGEN BIOSYNTHESIS

> **NIH NIH R37** · HAUPTMAN-WOODWARD MEDICAL RESEARCH INST · 1994 · $409,877

## Abstract

Our goal is 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 sex steroids, androgen aromatases, antibodies to
aromatase, and their molecular reactions and interactions.  Specific aims
are:  (1) Purification and characterization of multiple forms of aromatase
from human term placenta, (2) Production and utilization of antibodies
against aromatase, (3) Elucidation of mechanism of androgen aromatization,
(4) Irreversible inhibitors and affinity labeling of aromatase, and (5)
Solubilization, purification, and characterization of brain aromatase
system.  Androgen aromatase or estrogen synthetase is an enzyme which
catalyzes the conversion of androgen to estrogen.  Estrogens play many
important physiological roles through human development and are essential
to reproduction.  They are also involved in diseases including breast and
endometrium cancer.  Precise knowledge of the properties of this enzyme and
the specific antibodies may have important practical implications in
reproductive endocrinology, fertility regulation, and diagnosis and control
of carcinogenesis.  Development of irreversible inhibitors of aromatase may
lead to a chemotherapeutic application as a means of endocrine therapy to
control estrogen dependent carcinomas.

The methodology involves 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 crystallography
and spectroscopy, isotope distribution analysis, incubations with various
enzyme preparations, solubilization of membrane bound enzymes with
detergents, procedures to maintain enzymes in solution after removal of
detergents, purification of enzyme through various chromatographies
including immunoaffinity resins, identification of intermediates and
products of aromatase reaction by use of isotope techniques and GC-MS,
immunization of animals, hybridoma cultures, screening specific antibodies
by micro-aromatase assays, production of monoclonal antibodies in ascites
fluid, purification of immunoglobulins, immunohistochemical stainings,
radioimmunoassays, Western blot analysis, amino acid analysis, and amino
acid sequencing.

## Key facts

- **NIH application ID:** 2194873
- **Project number:** 5R37HD004945-24
- **Recipient organization:** HAUPTMAN-WOODWARD MEDICAL RESEARCH INST
- **SAM.gov UEI:** HVQYC8JZB9A6
- **Principal Investigator:** YOSHIO OSAWA
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $409,877
- **Award type:** 5
- **Project period:** 1970-07-01 → 1996-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2194873

## Citation

> US National Institutes of Health, RePORTER application 2194873, HUMAN DEVELOPMENT AND ESTROGEN BIOSYNTHESIS (5R37HD004945-24). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2194873. Licensed CC0.

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