There is mounting evidence that testosterone acts to maintain spermato-genesis through the interaction of this steroid with Sertoli cells. Thus, physiological situations which lead to a diminution of androgen concentration around Sertoli cells, or which lead to a reduction in the ability of these cells to respond to testosterone, could lead to a reduced production of testicular spermatozoa. In the male rat, testicular aging is characterized by a decline in sperm production and by a decrease in testosterone production by Leydig cells. We suggest that in the aged rat, decreased T production leads to decreased intratesticular testosterone concentration, and therefore, to diminished Sertoli cell function. While the consequences to spermatogenic cells of a hypofunctional Sertoli cells and a reduced number, or possibly reduced function, of stem spermatogonia. The experiments outlined in this application will test this hypothesis. First, wee will determine the effect of age and different intratesticular testosterone concentrations on the number and functions of rat Sertoli cells. Next, we will examine the effect of age on the number and rate of cell division of stem spermatogonia. Finally, we will examine how different intratesticular testosterone concentrations affect the number and function of stem spermatogonia in young and old rats.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG008321-03
Application #
3802776
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Type
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
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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
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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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