Abstract

The objective of this proposal is to develop aromatase (estrogen synthetase) inhibitors for clinical application in the areas of male and female contraception, endometriosis and premature labor. In order to determine how the compounds would be most effective as long-acting contraceptive agents in the female, studies would be conducted to investigate the role of estrogen in follicular recruitment and maturation in the rat ovary. Studies would be extended to the primate to determine the most effective schedule of treatment to inhibit estrogen production and ovulation. Aromatase inhibitor 4-hydroxyandrostene-3, 17-dione (4-OHA) would be evaluated in experimental endometriosis by studying the effect of 4-OHA on growth of endometrial explants sutured to the body wall of the rat. 4-OHA would also be evaluated in male rats for its effect on testicular aromatase, plasma testosterone concentrations and spermatogenesis. Hyperprolactinemia is a major cuase of infertility in women and during lactation prolactin levels are high. During the current grant period, inhibition of aromatase by prolactin was demonstrated in vivo in the rat. Studies are proposed to investigate the mechanism of prolactin inhibition of aromatase. In vitro cultures of rat ovarian granulosa cells will be used to study prolactin-mediated changes in gonadotropin and prolactin receptors, cAMP concentration and aromatase activity.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
2R01HD013909-09A1
Application #
3312367
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1980-09-01
Project End
1992-03-31
Budget Start
1989-04-01
Budget End
1990-03-31
Support Year
9
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
University of Maryland Baltimore
Department
Type
Schools of Medicine
DUNS #
003255213
City
Baltimore
State
MD
Country
United States
Zip Code
21201

  Publications

Njar, V C; Brodie, A M (1999) Comprehensive pharmacology and clinical efficacy of aromatase inhibitors. Drugs 58:233-55
Brodie, A M (1994) Aromatase inhibitors in the treatment of breast cancer. J Steroid Biochem Mol Biol 49:281-7
Koos, R D; Banks, P K; Inkster, S E et al. (1993) Detection of aromatase and keratinocyte growth factor expression in breast tumors using reverse transcription-polymerase chain reaction. J Steroid Biochem Mol Biol 45:217-25
Brodie, A M (1993) Aromatase, its inhibitors and their use in breast cancer treatment. Pharmacol Ther 60:501-15
Brodie, A (1991) Aromatase and its inhibitors--an overview. J Steroid Biochem Mol Biol 40:255-61
Banks, P K; Meyer, K; Brodie, A M (1991) Regulation of ovarian steroid biosynthesis by estrogen during proestrus in the rat. Endocrinology 129:1295-304
Inkster, S E; Brodie, A M (1991) Expression of aromatase cytochrome P-450 in premenopausal and postmenopausal human ovaries: an immunocytochemical study. J Clin Endocrinol Metab 73:717-26
Brodie, A M; Banks, P K; Inkster, S E et al. (1990) Aromatase and other inhibitors in breast and prostatic cancer. J Steroid Biochem Mol Biol 37:1043-8
Brodie, A M; Banks, P K; Inkster, S E et al. (1990) Aromatase inhibitors and hormone-dependent cancers. J Steroid Biochem Mol Biol 37:327-33
Brodie, A M; Hammond, J O; Ghosh, M et al. (1989) Effect of treatment with aromatase inhibitor 4-hydroxandrostenedione on the nonhuman primate menstrual cycle. Cancer Res 49:4780-4

Showing the most recent 10 out of 17 publications