INTERACTION BETWEEN BETA-ENDORPHIN AND ALPHA-MELANOCYTE-STIMULATING HORMONE IN THE CONTROL OF PROLACTIN AND LUTEINIZING-HORMONE SECRETION IN THE PRIMATE

The ability of αMSH, a POMC-derived peptide, to antagonize the effects of β-endorphin (βEP) on PRL and LH secretion was studied in the primate. Seven ovariectomized rhesus monkeys bearing chronic indwelling third ventricular catheters for peptide infusion were used for these studies. Peripheral blood samples for PRL and LH RIA were obtained every 15 min during a 3-h control period when saline was infused into the ventricle, followed by a 5-h period of peptide infusion at a rate of 25 μl/h. When βEP was infused at a dose of 5 μg/h, plasma PRL rose from a mean baseline of 3.5 ± 0.7 ng/ml to a peak of 21.3 ± 2.2 ng/ml. When the same animals were infused with 20 μg αMSH together with 5 μg βEP, the peak concentration of PRL was reduced to 8.2 ± 1.7 ng/ml (P < 0.001). When a higher dose of βEP (20 Mg/h) was infused, PRL rose to a peak of 38.2 ± 1.8 ng/ml. This response was again markedly blunted, and the peak PRL response was reduced to 7.3 ± 2.2 ng/ml when 20 μgβEP were infused together with 80 μg αMSH (P < 0.001). Analysis of the area under the plasma PRL concentration curves demonstrated a significant reduction in area during the 5-h infusion with βEP plus αMSH compared to that during infusion of βEP alone. The mean area was reduced from 3480 ± 570 ng min/ml after 5 μg βEP alone to 1030 ± 200 after 5 μg βEP plus 20 μg βMSH and from 6230 ± 990 after 20 μg βEP to 1020 ± 320 ng min/ml after 20 μg βEP plus 80 Mg αMSH (P < 0.01). Des-acetyl αMSH (80 μg) was also effective in reducing the PRL response to 830 ± 380 ng min/ml (P < 0.05). The suppression of pulsatile LH release by βEP was also attenuated by αMSH. During the 5-h infusion of βEP, total LH secretion was reduced to 65.9 ± 3.8% of that measured during the 3-h saline infusion compared to 87.2 ± 2.7% after infusion of βEP plus αMSH (P < 0.001) or 91.7 ± 4.1% after βEP plus des-acetyl αMSH (P < 0.05). The greatest suppression of LH release was seen during the last 2 h of infusion and was 44.6 ± 5.4% of baseline with βEP alone compared to 73.6 ± 3.9% after βEP plus αMSH (P < 0.001). We conclude that αMSH can effectively antagonize the actions of αMSH on pituitary PRL and LH release in the primate. This antagonism with respect to LH release differs from what has been reported in the rat and may be unique to the primate. These findings suggest that differential posttranslational processing of POMC may serve as a regulator of PRL and gonadotropin secretion in the primate. © 1990 by The Endocrine Society.