Development of Leydig Cell Tumors and Onset of Changes in the Reproductive and Endocrine Systems of Aging F344 Rats2

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Abstract
The age-dependent onset of spontaneous testicular interstitial cell tumors was examined in F344 male rats. Light microscopy of testes established that nodular interstitial cell hyperplasia was evident in 3 of 5 12-month-old rats and in 5 of 5 rats at 15, 18, 21, and 24 months of age. Involution of the seminiferous epithelium was evident in all testes exhibiting extensive interstitial cell proliferation. Striking increments in serum prolactin and estradiol levels were noted with advancing age, whereas serum levels of follicle-stimulating hormone were unequivocally lower at 21 and 24 months than at 6 months of age. No measurable changes were detected in serum testosterone concentrations between 6 and 18 months of age, but marked increments in this androgen, without any measurable change in circulating luteinizing hormone titers, were apparent in 21- and 24-month-old rats. These findings point to a dynamic relationship between testicular interstitial cell tumorigenesis and age-related changes in the synthesis and/or secretion of gonadal and adenohypophyseal hormones.