Much is known about neuropeptides that stimulate the hypothalamic-pituitary-gonadal axis, however, less is known about peptides that may inhibit this pathway. Recently, a peptide (RFRP-3) was shown to act as a luteinizing hormone inhibitor in males. The purpose of this study was to investigate the effects of RFRP-3 on sex behavior and the estrus-related increase in luteinizing hormone levels in female rats. We hypothesized that central ICV administration of RFRP-3 (500 ng) would suppress both female sex behavior and LH levels in ovariectomized, hormone-primed female rats. Each animal received both RFRP-3 and vehicle, counterbalanced for order, with injections separated by at least one week. For the sex behavior study, after RFRP-3 or vehicle infusion the females were placed in a cage with an experienced male and sex behavior was recorded for one hour (i.e., lordosis, mounts, intromissions and ejaculations). For the measurement of LH levels, blood was collected by tail nick 30 minutes and 90 minutes after the RFRP-3 or vehicle infusion. LH levels were measured in the same animals that had been previously tested in the sex behavior study. Results indicate that RFRP-3 suppressed sexual receptivity in the female rat by significantly decreasing lordosis quotient between 45 and 90 minutes post-RFRP-3 injection, p<0.05. In addition, the LH surge was suppressed in RFRP-3 injected animals compared with vehicle-injected controls (p = 0.004). These results suggest that RFRP-3 may act as an important regulator of LH levels and sex behavior during estrus.
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