Diminished luteinizing hormone pulse frequency and amplitude with aging in the male rat

Abstract

Aging in the male rat is associated with a reduction in circulating testosterone levels. One possible cause of this decline is an age-related alteration of central nervous system-mediated LH secretion. To examine the effects of age on the hypothalamo-hypophyseal system, in the absence of gonadal steroid feedback, we studied the pattern of pulsatile LH secretion in castrate male Sprague-Dawley rats, aged 3 months (young), 8 months (middle-aged), and 26 months (old). All animals were castrated, and after 3 weeks, they were implanted with indwelling atrial catheters. One day later, duplicate 25 microliters blood samples were obtained at 4-min intervals for 4 h, while the animals were awake and unrestrained. Serum levels of LH, FSH, and testosterone were measured in animals before castration, and blood LH levels were measured in the postcastration, repeated sampling studies. After castration, middle-aged and old animals exhibited significantly lower mean serum LH levels, associated with a diminished amplitude of LH secretory episodes compared to young rats. In the oldest group, LH pulse frequency was significantly lower compared to middle-aged and young animals. Since the control of LH secretory episodes resides in the central nervous system, we propose that alterations in frequency of LH pulses observed in the aged, castrate male rat are the result of a diminished functional capacity of LHRH-containing neurons or of neurotransmitters that modulate their activity in the aging brain.