The Brown Norway rat as a model of male reproductive aging: evidence for both primary and secondary testicular failure.

Abstract

In man, aging is associated with both primary and secondary testicular dysfunction. In contrast, most studies in male rat models of aging have demonstrated only secondary testicular failure. We previously reported that testes from aging male F344 rats secrete excessive progesterone (P), which may suppress gonadotropin secretion and confound aging studies. To determine whether the male Brown Norway (BN) rat is a more suitable aging model, trunk blood was collected from intact (sham-operated) and orchidectomized young (3 mo), middle-aged (13 mo), old (23 mo), and senescent (28-30 mo) animals. Testosterone (T), estradiol (E2), P, prolactin (PRL), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured by RIA. In intact rats, T levels declined with aging, while LH was unchanged, and FSH increased progressively with aging. In contrast to F344 rats, no age-related increases in P or E2 occurred, nor did PRL or other steroid hormones increase. In the absence of testicular feedback (orchidectomized rats), FSH and LH declined progressively with aging. These findings suggest that, as in men, aging male BN rats manifest both primary and secondary testicular failure, and do not exhibit decreased gonadotropin levels secondary to excessive steroid or PRL secretion. Therefore, the BN rat appears to be the best available rat model for studies of male reproductive aging.