Gene expression in brown Norway rat Leydig cells: Effects of age and of age-related germ cell loss

There is a marked reduction in circulating T and a commensurate decrease in Leydig cell function in males during aging. Aging is also accompanied by p rogressive loss of germ cells, leading to testicular atrophy. However, in a ged animals, there is no difference in T production by Leydig cells from no nregressed testes and from regressed testes. We hypothesize that there are changes in Leydig cell gene expression that accompany aging, and that diffe rent changes in gene expression result from testicular regression. To test this hypothesis, the expression of stress response genes was compared in Le ydig cells isolated from young rat testes, from aged testes that were not r egressed, and from aged testes that were regressed, using an array approach . Similar numbers of transcripts (n = 56-63) were detected in Leydig cells isolated from all three groups of rats. Among these, 21 transcripts were in creased in Leydig cells of testes from aged nonregressed animals compared w ith cells from young animals; 23 were increased with subsequent testicular regression. Only 3 of these transcripts were in common. Thus, age and testi cular regression affected Leydig cell transcripts in dramatically different ways. Furthermore, none of the transcripts that decreased when comparing L eydig cells of young and aged nonregressed animals were the same as those t hat decreased when comparing aged nonregressed and aged regressed animals. In individual gene families, the steady state concentrations of transcripts in Leydig cells from aging and aging regressed testes often differed. Thus , there are major differences in the expression of a wide variety of stress response genes in Leydig cells associated with aging and testicular regres sion.