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Gene Expression in Brown Norway Rat Leydig Cells: Effects of Age and of Age-Related Germ Cell Loss

Departments of Pharmacology and Therapeutics, and Obstetrics and Gynecology, McGill University (P.S., B.R.), Montréal, Québec, Canada H3G 1Y6; and Division of Reproductive Biology, Department of Biochemistry and Molecular Biology, The Johns Hopkins University School of Hygiene and Public Health (H.C., B.R.Z.), Baltimore, Maryland 21205

Address all correspondence and requests for reprints to: Dr. B. Robaire, Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir William Osler, Montréal, Québec, Canada H3G 1Y6. E-mail: brobaire{at}pharma.mcgill.ca

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 progressive loss of germ cells, leading to testicular atrophy. However, in aged animals, there is no difference in T production by Leydig cells from nonregressed testes and from regressed testes. We hypothesize that there are changes in Leydig cell gene expression that accompany aging, and that different changes in gene expression result from testicular regression. To test this hypothesis, the expression of stress response genes was compared in Leydig cells isolated from young rat testes, from aged testes that were not regressed, 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 increased in Leydig cells of testes from aged nonregressed animals compared with cells from young animals; 23 were increased with subsequent testicular regression. Only 3 of these transcripts were in common. Thus, age and testicular regression affected Leydig cell transcripts in dramatically different ways. Furthermore, none of the transcripts that decreased when comparing Leydig cells of young and aged nonregressed animals were the same as those that 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 regression.

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