Age-related changes in the male reproductive tract are of importance for a number of reasons, including: 1) the population of the U.S. is aging rapidly; 2) a number of diseases of aged men, such as benign prostatic hyperplasia and prostatic cancer, depend upon testicular hormones; 3) other endocrine diseases, such as osteoporosis, are likely to become major problems in geriatric males; 4) aga-related changes in drug and xenobiotic effects have been shown; and 5) couples are waiting until later in life to have children. The male reproductive tract offers many advantages for studies of age-related phenomena, including: 1) experimental manipulation of the tests/epididymides is unlikely to cause death or morbidity; 2) much is known about the regulation of the male tract; and 3) the male reproductive system is an excellent model for generalized aging because it is possible to study, at once, the influence of age on cells that have different proliferative capacities and are at different stages of differentiation. Thus, there are cells that are proliferating rapidly by mitosis (spermatogonia, prostatic epithelia cells), undergoing meiosis (spermatocytes), permanently postreplicative (Sertoli cells), slowly turning over (Leydig cells), differentiating (spermatids), terminally differentiated (spermatozoa), and exquisitely sensitive to hormones and to changes in testicular function (epididymal and prostatic epithelia cells). In the rat, as in the human, striking changes occur with aging, including reduced secretion of testosterone, diminished germ cell production, reduced numbers of testicular and epididymal sperm, atrophy of the seminiferous epithelium, and increased sensitivity of the prostate gland to androgens. The major objectives of this program project application are to elucidate the critical structural and functional changes associated with aging of Leydig (Drs. Zirkin and Wright, Project 1), prostatic (Dr. Brown, Project 2), Sertoli/germ (Drs. Zirkin and Wright, Project 1), spermatozoal (Dr. Robaire, Project 3) and epididymal (Dr. Robaire, Project 3) cells, and to determine the mechanism by which such changes occur.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG008321-10
Application #
6168060
Study Section
Special Emphasis Panel (ZAG1-BJB-4 (J1))
Program Officer
Bellino, Francis
Project Start
1994-05-12
Project End
2002-03-31
Budget Start
2000-04-15
Budget End
2001-03-31
Support Year
10
Fiscal Year
2000
Total Cost
$800,449
Indirect Cost
Name
Johns Hopkins University
Department
Type
Schools of Public Health
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Jervis, Kathryn M; Robaire, Bernard (2004) The effects of long-term vitamin E treatment on gene expression and oxidative stress damage in the aging Brown Norway rat epididymis. Biol Reprod 71:1088-95
Zubkova, Ekaterina V; Robaire, Bernard (2004) Effect of glutathione depletion on antioxidant enzymes in the epididymis, seminal vesicles, and liver and on spermatozoa motility in the aging brown Norway rat. Biol Reprod 71:1002-8
Anway, Matthew D; Folmer, Janet; Wright, William W et al. (2003) Isolation of sertoli cells from adult rat testes: an approach to ex vivo studies of Sertoli cell function. Biol Reprod 68:996-1002
Ezer, Nadine; Robaire, Bernard (2003) Gene expression is differentially regulated in the epididymis after orchidectomy. Endocrinology 144:975-88
Jervis, Kathryn M; Robaire, Bernard (2002) Changes in gene expression during aging in the Brown Norway rat epididymis. Exp Gerontol 37:897-906
Banerjee, Partha P; Banerjee, Subhadra; Brown, Terry R (2002) Bcl-2 protein expression correlates with cell survival and androgen independence in rat prostatic lobes. Endocrinology 143:1825-32
Chen, Haolin; Hardy, Matthew P; Zirkin, Barry R (2002) Age-related decreases in Leydig cell testosterone production are not restored by exposure to LH in vitro. Endocrinology 143:1637-42
Culty, Martine; Luo, Lindi; Yao, Zhi-Xing et al. (2002) Cholesterol transport, peripheral benzodiazepine receptor, and steroidogenesis in aging Leydig cells. J Androl 23:439-47
Luo, L; Chen, H; Zirkin, B R (2001) Leydig cell aging: steroidogenic acute regulatory protein (StAR) and cholesterol side-chain cleavage enzyme. J Androl 22:149-56
Jervis, K M; Robaire, B (2001) Dynamic changes in gene expression along the rat epididymis. Biol Reprod 65:696-703

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