Abstract
The neuropeptide 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 either 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 (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 intravenous injections of RFRP-3 (6x50 μ g) in ovariectomized ewes had no effect on plasma LH pulsatility. In intact ewes a bolus injection (500 μ g) or an injection (250, 500 or 1000 μ g) followed by 4-hour perfusion (250, 500 or 1000 μ g h(-1)) of RFRP3 had no effect on the LH pulse induced by kisspeptin (6.5 μ g). In ovariectomized estrogen-replaced ewes the LH surge induced by estradiol benzoate was not modified by a 24-hour perfusion of RFRP-3 (500 μ g h(-1)). Finally, while treatment with RF9 induced a robust release of LH, treatment with a more selective RFRP-3 receptor antagonist, GJ14, resulted in no evident increase of LH. In contrast to the inhibitory effect previously suggested, our data are more consistent with the concept that RFRP-3 has no direct effect on LH secretion in ewes and that RF9 effect on LH release is likely not RFRP-3 receptor-mediated. Hence, RFRP-3 has probably a minor role on the control of LH secretion in the ewe.