Gonadotropin regulation in middle-aged male rats.

Gonadotropin regulation was compared in middle-aged (13 months old) and young adult (3 months old) male rats. Two experiments were conducted on castrated animals given testosterone in Silastic capsules; the dimensions were adjusted to insure equivalent circulating testosterone levels in the two age groups, as validated by RIA. Plasma LH and FSH were also measured by RIA. In Exp 1, each animal was implanted immediately after castration with multiple capsules sufficient to maintain tonic suppression of LH. One capsule was removed each week, thereby reducing testosterone levels in 0.4 ng/ml steps, in order to determine the testosterone level (threshold) at which LH is released from tonic suppression. Middle-aged animals had a threshold 50% lower than young animals, requiring much less testosterone to maintain tonic LH levels. They also showed an attenuated rise in LH and FSH after release from tonic suppression. In Exp 2, long term castrates were given capsules which produced plasma testosterone levels of approximately 1.5 ng/ml in order to evaluate the negative feedback effects of testosterone on elevated LH levels. The testosterone was more effective in suppressing LH in middle-aged rats than in young animals. These results indicate that: 1) middle-aged male rats develop an increased sensitivity to the feedback effects of testosterone, and this increased sensitivity is operative within the normal physiological range of LH and testosterone; and 2) middle-aged animals have a reduced capacity to increase LH and FSH levels after release from tonic suppression. These changes in gonadotropin regulation can account, to a large extent, for the pituitary-testicular decline which develops during middle age in male rats.