No Evidence That RFamide-Related Peptide 3 Directly Modulates LH Secretion in the Ewe

The neuropeptide RFamide-related peptide 3 (RFRP-3) has been implicated in the control of gonadotropin secretion in both birds and mammals. However, in mammals, depending on species, sex and photoperiod, inhibitory, excitatory, or no effect of RFRP-3 on the plasma concentration of LH has been reported. In the ewe, treatment with RFRP-3 either reduced LH concentration or had no effect, and treatment with an RFRP-3 receptor antagonist (ie, RF9) resulted in increased concentration of plasma LH. To clarify these conflicting results in the present study, a set of experiments was performed in ewes. Multiple iv injections of RFRP-3 (6 × 50 μg) in ovariectomized ewes had no effect on plasma LH pulsatility. In intact ewes a bolus injection (500 μg) or an injection (250, 500, or 1000 μg) followed by a 4-hour perfusion (250, 500, or 1000 μg · h−1) of RFRP-3 had no effect on the LH pulse induced by kisspeptin (6.5 μg). In ovariectomized, estrogen-replaced ewes, the LH surge induced by estradiol benzoate was not modif...