FAILURE OF NALOXONE TO STIMULATE LUTEINIZING-HORMONE SECRETION DURING PREGNANCY AND STEROID TREATMENT OF OVARIECTOMIZED BEEF-COWS

The response of serum luteinizing hormone (LH) to naloxone, an opiate antagonist, and gonadotropin-releasing hormone (GnRH) was measured in cows in late pregnancy to assess opioid inhibition of LH. Blood samples were collected at 15-min intervals for 7 h. In a Latin Square arrangement, each cow (n = 6) received naloxone (0, 0.5, and 1.0 mg/kg BW, i.v.; 2 cows each) at Hour 2 on 3 consecutive days (9 ± 2 days prepartum). GnRH (7 ng/kg body weight, i.v.) was administered at Hour 5 to all cows on each day. Mean serum LH concentrations (x ± SE) before naloxone injection were similar (0.4 ± 0.1 ng/ml), with no serum LH pulses observed during the experiment. Mean serum LH concentrations post-naloxone were similar (0.4 ± 0.1 ng/ml) to concentrations pre-naloxone. Mean serum LH concentrations increased (p < 0.05) following GnRH administration (7 ng/kg) and did not differ among cows receiving different dosages of naloxone (0 mg/kg, 1.44 ± 0.20; 0.5 mg/kg, 1.0 ± 0.1; 1.0 mg/kg, 0.9 ± 0.1 ng/ml). In Experiment 2, LH response to naloxone and GnRH was measured in 12 ovariectomized cows on Day 19 of estrogen and progesterone treatment (5 μg/kg BW estrogen; 0.2 mg/kg BW progesterone) and on Days 7 and 14 after steroid treatment. On Day 19, naloxone failed to increase serum LH concentrations (Pre: 0.4 ± 0.1; Post: 0.4 ± 0.1 ng/ml) after 0, 0.5, or 1.0 mg/kg BW. Before administration of naloxone, mean serum LH concentration and LH pulse frequency were greater (p < 0.05) on Days 7 and 14 after steroid treatment than on Day 19 of steroid treatment. Naloxone increased (p < 0.05) serum LH concentrations to 5.5 ± 0.9 and 3.9 ± 0.4 on Day 7 and to 7.1 ± 0.8 and 6.1 ± 0.6 ng/ml on Day 14 after steroid treatment for 0.5- and 1.0-mg/kg doses, respectively. These results demonstrate that during pregnancy or ovarian steroid treatment, naloxone, at the dosage used, was either not sufficient to stimulate release of GnRH or endogenous GnRH released was insufficient to increase serum LH because of deficient pituitary stores or pituitary responsiveness. Naloxone antagonized opioid inhibition of LH secretion at 7 and 14 days after termination of steroid treatment and supports the hypothesis that ovarian steroids have residual effects on opioid inhibition of LH.