Luteinizing hormone pulse frequency is increased by arginine infusion in prepubertal sheep

Puberty in sheep is initiated by a complex neuroendocrine interplay which cascades into an increased LH pulsatility at this time. Blood-borne amino acids have been proposed as metabolic signals for the stimulation of GnRH/LH secretion, a mandatory requirement for pubertal onset. In previous experiments we have demonstrated that a 1 h infusion of L-arginine (ARG) was capable of stimulating the LH secretion in prepubertal ewes. The aim of the present study was to further examine the effect of an intravenous infusion of ARG on LH secretion. Prepubertal ewes were infused for 6 h with 15 (Group ARG15, n = 5) or 30 g (Group ARG30, n = 5) of L-ARG dissolved in 500 mL saline (pH 7.4), while saline was administered as control (Group S, n = 5). Since ARG is metabolized to ornithine (ORN), equimolar doses of L-ORN were additionally tested (Group ORN12 and ORN24, n = 5, respectively). Blood samples were obtained at 15 minute intervals during and after experimental infusions to characterize the LH pulsatile secretion. The resulting hormone data arrays were searched for significant fluctuations by the PULSAR program. The LH pulse frequency was found to be higher in groups of ARG treated than in saline or ORN infused sheep during the 6-h infusion period: 5.6 +/- 1.0 (ARG15) vs. 5.0 +/- 0.5 (ARG30) vs. 2.0 +/- 0.9 (S, p < 0.01) vs. 3.4 +/- 0.9 (ORN12) vs. 3.4 +/- 0.9 pulses/6 h (ORN24, p < 0.05). The total number of pulses was higher in ARG infused lambs than in saline or ORN infused animals: 11.2 +/- 1.2 (ARG15) vs. 10 +/- 1.1 (ARG30) vs. 13.8 +/- 1.4 (S) vs. 5.8 +/- 1.7 (ORN12) vs. 5.8 +/- 2.0 pulses/12h (ORN24), respectively. The LH mean secretion was comparable during both 6-h periods in all groups. Results of our experiments demonstrate increased LH pulse frequencies during ARG infusions, suggesting an action of ARG to stimulate hypothalamic GnRH release. Thus, ARG may be a critical determinant for enhanced LH pulsatility as a prerequirement for the onset of puberty in the sheep.