Our long term goal is to understand the role of tissue degradation in abnormal growth of the human prostate, namely, benign prostatic hyperplasia and prostatic carcinoma. The present proposal deals with the study of basic biology of prostatic regression in the rat. Since the rat prostate involutes at an accelerated, yet predictable, rate upon castration in the host, many biological parameters, currently unclear to us, can be identified and characterized as events associated with prostatic regression. These events are likely pre-programmed and are likely destined to cellular destruction. It should be pointed out that it is not the objective of the present proposal to study the mechanism of action of testosterone and prolactin in the rat prostate. If results of these studies are able to contribute to our knowledge in hormone action, it is not done so by our design. The following three areas are proposed: (1) Study of protein synthesis in regressing prostate: Results of our previous studies have continuously supported the concept that prostatic regression involves an active metabolic process. We propose that, during prostatic regression, a few protein species are actively synthesized to facilitate the regressive process. With the technique of two-dimensional electrophoresis, it is possible for us to compare different protein species that are synthesized by the normal prostate and by the regressing prostate. (2) Characterization of degradative enzymes in regressing prostate: Earlier results indicate that activities of degradative enzymes play an important role in tissue regression. In addition to the study of synthesis and degradation, we propose to study cellular distribution of various degradative enzymes. We will first characterize cathepsin D and prostatic acid phosphatase, since we have developed the antibody against the former and identified the latter in the rat prostate. As other important proteins are identified, they will be added to the list of our investigation. (3) Study of the effect of prolactin on degradative enzymes: Results of our previous studies have indicated that prolactin is not likely to participate in the synthetic activities in the regressing prostate. We propose that the effect of prolactin in causing a delay in prostatic regression lies in its ability to alter the activities of intracellular degradative enzymes. We plan to study the effect of prolactin on cell death, on pattern of protein synthesis and on distribution of degradative enzymes in the rat prostate. The fate of prolactin in the regressing prostate will also be studied.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD011611-12
Application #
3311626
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1977-12-01
Project End
1991-06-30
Budget Start
1989-07-01
Budget End
1991-06-30
Support Year
12
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Schacht, M J; Niederberger, C S; Garnett, J E et al. (1992) A local direct effect of pituitary graft on growth of the lateral prostate in rats. Prostate 20:51-8
Lee, C; Sensibar, J A; Sinha, A A et al. (1992) Induction of specific gelatinolytic proteinases in the lateral prostate of rats by ectopic pituitary grafts. Biol Reprod 46:671-9
Darras, F S; Lee, C; Huprikar, S et al. (1992) Evidence for a non-androgenic role of testis and epididymis in androgen-supported growth of the rat ventral prostate. J Urol 148:432-40
Sensibar, J A; Griswold, M D; Sylvester, S R et al. (1991) Prostatic ductal system in rats: regional variation in localization of an androgen-repressed gene product, sulfated glycoprotein-2. Endocrinology 128:2091-102
Lee, C; Sensibar, J A; Dudek, S M et al. (1990) Prostatic ductal system in rats: regional variation in morphological and functional activities. Biol Reprod 43:1079-86
Sensibar, J A; Liu, X X; Patai, B et al. (1990) Characterization of castration-induced cell death in the rat prostate by immunohistochemical localization of cathepsin D. Prostate 16:263-76
Sensibar, J A; Alger, B; Tseng, A et al. (1990) Proteins of the rat prostate. III. Effect of testosterone on protein synthesis by the ventral prostate of castrated rats. J Urol 143:161-6
Dalton, D P; Lee, C; Huprikar, S et al. (1990) Non-androgenic role of testis in enhancing ventral prostate growth in rats. Prostate 16:225-33
Lee, C; Sherwood, E R; Sensibar, J A et al. (1989) Profile matching and profile subtraction: application of computer-based image analysis system for two-dimensional electrophoresis gels. Biotechniques 7:374-8
Lee, C; Hu, S E; Lok, M S et al. (1988) Microcomputer-based image analysis systems for two-dimensional electrophoresis gels. Biotechniques 6:216-24

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