REPRODUCTIVE AGING IN THE MALE BROWN-NORWAY RAT - A MODEL FOR THE HUMAN

Previous studies in the Sprague-Dawley rat have demonstrated that male reproductive aging is primarily a neuroendocrine dysfunction characte rized by decreased pulsatile LH secretion leading to low serum testost erone (T) levels, whereas sperm production is relatively well maintain ed. In contrast to the Sprague-Dawley rat, the Brown-Norway (BN) rat h as a longer life span, does not become obese, and experiences fewer ag e-related tumors of the endocrine or reproductive system, thus providi ng a disease-free model for studying male reproductive aging. We studi ed the changes in serum hormone levels and related these alterations t o testicular T production, Leydig cell morphometry, and spermatogenesi s in young (6 months), aging (22 months), and old (30 months) BN rats. Low serum T levels were associated with decreased LH levels in the 22 -month-old (T, 0.58 +/- 0.08 ng/ml; LH, 0.45 +/- 0.06 ng/ml) and 30-mo nth-old rats (T, 0.63 +/- 0.10 ng/ml; LH, 0.34 +/- 0.04 ng/ml) compare d to those in young rats (T, 1.35 +/- 0.30 ng/ml; LH, 0.79 +/- 0.10 ng /ml). In vitro Leydig cell T production, basally and after stimulation by LH, was similar in young and old rats. The total testicular T cont ent was lower in 30- than in 6-month-old rats. Testicular morphometry showed smaller Leydig cell volume in the old (857 +/- 97 mum3) than in the young rats (1387 +/- 103 mum3), although their number per testis remained unchanged (6 months, 22.7 +/- 1.6 x 10(6)/testis; 30 months, 25.2 +/- 3.1 X 10(6)/testis). In contrast, a marked (68.4%) reduction in the total number of Sertoli cell per testis was noted in the 30-mon th-old rats. The proportion of the testis occupied by seminiferous tub ules was also reduced in the old rats. Significant (P < 0.05) age-rela ted reductions occurred in tubule diameter, length of tubules, and vol ume of tubules and their lumens. The testicular sperm concentration an d total sperm production were significantly reduced in the 22- and 30- month-old rats. These changes in seminiferous tubule function in the o ld rats were associated with low serum and testicular inhibin and high serum FSH levels. We conclude that aging in the reproductive axis of the BN rat is manifested by 1) lower serum T levels due to decreased p ituitary LH stimulation of endogenous T production, and 2) decreased s eminiferous tubule function accompanied by elevated FSH levels indicat ive of a primary testicular disorder. Because of the coexisting testic ular and hypothalamic pituitary dysfunction with aging, the BN rat is a better model to study human male reproductive aging than the Sprague -Dawley rat.