Effects of Long-Term Ovariectomy, Repeated Pregnancies and Naloxon&

Aging of the female reproductive system may be regulated by changes at the hypothalamic, pituitary, and ovarian levels. Long-term ovariectomy (LT-OVX) and/or multiple pregnancies delay age-related deterioration of several parameters of reproductive potential in rodents. We tested whether long-term suppression of cyclic ovarian hormone release that is normally associated with the 4- to 5-day estrous cycle decelerates age-related decreases in the frequency of luteinizing hormone (LH) pulses to assess whether hormonal milieu influences the rate of aging of the pulse generator. We determined thepercentageof rats exhibiting pulsatile LH secretion, mean LH levels, and amplitude and frequency of LH pulses in seven groups of ovariectomized (OVX) rats. Young (3-4 mo), middle-aged (8-10 mo), and old (18-22 mo) virgin rats, ovariectomized 4 wk (4WK-OVX) prior to experimentation, were used to determine the effect of age. The effect of long-term ovarian hormone deprivation was tested by ovariectomizing ratsat 2-3 mo of age and using them when they were middle-aged (8-10 months) or old (18-22 mo). The effect of deprivation of cyclic increases in ovarian hormones associated with repeated estrous cycles was tested by using retired breeder (RB) rats that had been ovariectomized 4 wk prior to experimentation. Each rat was implanted with a right atrial cannula and bled the next day at 10-mm intervals for 3 h. To test whether the pattern of LH pulses was affected by opiates, rats were bled at 10-mm intervals for I h and then treated with naloxone (2 or 10 mg/kg, iv.) and bled for an additional 3 h. A normal pulsatile pattern of LH release was observed in all young 4WK-OVX rats. In middle-aged 4WK-OVX rats, the percentage of rats exhibiting detectable pulses, the pulse frequency, and the pulse amplitude were significantly lower than in young 4WK-OVX rats. Old 4WK-OVX rats exhibited a further significant deterioration in all parameters assessed. Long-term ovariectomy attenuated the age-related decline in the proportion of middle-aged and old rats exhibiting pulsatile LH secretion, and the changes in mean LH and LH pulse amplitude. Repeated pregnancies also delayed age-related declines in the proportion of rats exhibiting a pulsatile pattern of LH secretion and mean LH levels. However, neither means of ovarian hormone deprivation delayed the agerelated decrease in pulse frequency. Naloxone administration to 4WK-OVX young and middle-aged and RB rats stimulated LH transiently, but it did not restore LH pulse amplitude or pulse frequency to values characteristic of young rats. Naloxone had no effect in old rats or LT-OVX rats of any age. The data demonstrate that aging involves a deterioration in several aspects of the pattern of LH secretion. Changes in responsiveness to naloxone do not account for the differences in the pattern of LH release. Only some of these parameters are influenced by exposure to estrogen. The age-related decrease in LH pulse frequency, which is thought to reflect the integrity of the neural pulse generator, is not prevented by ovarian hormone deprivation. The data suggest that age-related deterioration of the pulse generator cannot be attenuated by decreasing exposure to ovarian hormones.