We have found that the maximal capacity of the testes of otherwise healthy Brown Norway rats to produce testosterone declines significantly with age, as do serum and intratesticular testosterone concentrations. Additionally, testicular production of spermatozoa declines, differentiating germ cells are lost, and the seminiferous tubules develop increasing degrees of atrophy. The objectives of this project are to address the possible mechanism(s) by which aging Leydig cell lose steroidogenic function, and the possible consequences of Leydig cell aging on spermatogenesis. In experiments proposed under Specific Aim 1, we will determine the extent to which changes in Leydig cell number and structure, diminished or lost Leydig cell steroidogenic enzymes and the steady state levels of their mRNAs, LH, account for age-related decreases in the ability of Leydig cells of aged rat testes to produce testosterone.
In Specific Aim 2, we will ask whether the Leydig cells that are restored to the testes of old rats after their experimental elimination from the aged testis have the structural and functional characteristics of those in young or aged rats, and when and how the restored Leydig cells become hypofunctional with respect to their ability to produce testosterone.
In Specific Aim 3, we will determine the extent to which are experimental elimination of LH-responsive Leydig cell products, or of Leydig cells themselves, affects age-related losses of germ cells from the seminiferous epithelium of aging rats. As a corollary, we will determine whether the exogenous administration of testosterone to rats as they age will prevent germ cell losses.
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