Abstract

Data continue to accumulate supporting the hypothesis that circulating estrogens may function as promotor agents during the development of endometrial cancer in postmenopausal women. The theme of this research proposal is to comprehensively examine the role of circulating estrogens in this process. The presence of estrogens in the circulation of postmenopausal women will be defined in terms of biological as well as immunological activity. The in vivo transport of circulating estrogens into the uterus will be determined. The intracellular metabolism of circulating estrogens by endometrial cells and the influence of this metabolism on nuclear binding of these hormones will be determined. The actions of circulating estrogens on endometrial cell function will be evaluated using promotion of cellular growth and protein synthesis (progesterone receptors) as markers of estrogenic activity. These studies will be performed using blood and endometrial tissue samples from postmenopausal women at low risk (slender women, not on estrogen replacement) and at high risk (obese women) for the development of this tumor and from patients who have the disease. These studies should comprehensively define the role of circulating estrogens in the development of this tumor in terms of presently available techniques.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA023093-07
Application #
3166021
Study Section
Endocrinology Study Section (END)
Project Start
1984-05-01
Project End
1987-04-30
Budget Start
1985-05-01
Budget End
1986-04-30
Support Year
7
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095

  Publications

Chaudhuri, G; Steingold, K A; Pardridge, W M et al. (1988) TeBG- and CBG-bound steroid hormones in rabbits are available for influx into uterus in vivo. Am J Physiol 254:E79-83
de Ziegler, D; Cedars, M I; Randle, D et al. (1987) Suppression of the ovary using a gonadotropin releasing-hormone agonist prior to stimulation for oocyte retrieval. Fertil Steril 48:807-10
Steingold, K A; Pardridge, W M; Judd, H L et al. (1987) The effects of membrane permeability and binding by human serum proteins on steroid influx into the rabbit uterus. Am J Obstet Gynecol 157:1543-9
Judd, H L (1987) Oestrogen replacement therapy: physiological considerations and new applications. Baillieres Clin Endocrinol Metab 1:177-206
Steingold, K; De Ziegler, D; Cedars, M et al. (1987) Clinical and hormonal effects of chronic gonadotropin-releasing hormone agonist treatment in polycystic ovarian disease. J Clin Endocrinol Metab 65:773-8
Chaudhuri, G; Verheugen, C; Pardridge, W M et al. (1987) Selective availability of protein bound estrogen and estrogen conjugates to the rat kidney. J Endocrinol Invest 10:283-90
Cefalu, W T; Pardridge, W M; Chaudhuri, G et al. (1986) Serum bioavailability and tissue metabolism of testosterone and estradiol in rat salivary gland. J Clin Endocrinol Metab 63:20-8
Steingold, K A; Lobo, R A; Judd, H L et al. (1986) The effect of bromocriptine on gonadotropin and steroid secretion in polycystic ovarian disease. J Clin Endocrinol Metab 62:1048-51
Steingold, K A; Cefalu, W; Pardridge, W et al. (1986) Enhanced hepatic extraction of estrogens used for replacement therapy. J Clin Endocrinol Metab 62:761-6
Steingold, K A; Judd, H L; Nieberg, R K et al. (1986) Treatment of severe androgen excess due to ovarian hyperthecosis with a long-acting gonadotropin-releasing hormone agonist. Am J Obstet Gynecol 154:1241-8

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