Effects of Chronic Luteinizing Hormone-Releasing Hormone Administration on Gonadotropin Dynamics of Adult Male Rats 1

Abstract

The studies reported herein were conducted to determine the sequential effects of chronic luteinizing hormone-releasing hormone (LHRH) or D-Trp⁶-Pro⁹-NEt-LHRH (LHRH_a) administration on LH, FSH, and T dynamics. Adult male rats (n = 6/group) were injected subcutaneously with 1 μg of LHRH or LHRH_a once daily at 8:00 am for 1 through 7 days. The rats were decapitated at various times postinjection and their blood, pituitaries, and testes collected. When measured 24 hr after each injection, significant (P ≤ 0.01) decreases were observed in concentrations of serum T and pituitary LH and FSH as well as testicular volume; whereas basal serum concentrations of LH and FSH were significantly (P ≤ 0.01) elevated from Days 3 through 7 in both LHRH and LHRH_a-treated rats. LH was secreted in a large single peak 1 hr after each LHRH injection, increasing 54-fold above preinjection concentrations on Day 1 and lessening to a 34-fold increase on Days 3 through 7. The magnitude of the FSH response was not altered with chronic LHRH treatment. The peak responses of both LH and FSH were blunted with LHRH_a treatment. When rats were castrated after 5 days of LHRH treatment, the castration-induced rise in serum FSH concentration was normal, whereas the LH rise was delayed and blunted. These data indicate that: (1) Chronic treatment with LHRH or LHRH_a results in elevated basal serum gonadotropin concentrations and reduced basal serum testosterone concentrations and pituitary LH and FSH concentrations. (2) Chronic treatment with LHRH reduces the serum LH response (but not the FSH response) to subsequent LHRH injections. Furthermore, chronic treatment with essentially an equimolar dose of a potent LHRH agonist (d-Trp⁶-Pro⁹-NEt-LHRH) blunts both the LH and the FSH response to subsequent LHRH agonist injections. Furthermore, chronic treatment with essentially an equimolar dose of a potent LHRH agonist (D-Trp⁶-Pro⁹-NEt-LHRH) blunts both the LH and the FSH response to subsequent LHRH agonist injections. (3) FSH responses to castration are not altered by chronic LHRH treatment, whereas LH responses to castration are decreased. Treatment with a potent LHRH agonist prevents the normal rise in serum LH and FSH concentrations following castration.