Effects of insulin-like growth factor-1 on luteinizing hormone secretion in sheep

Circulating insulin-like growth factor-1 (IGF-1) may be involved in nutritional modulation of reproductive status. Acute effects of IGF-1 on luteinizing hormone (LH) secretion were studied in two experiments, each using eight castrate male sheep surgically prepared with an elevated carotid artery, four with (E+) and four without (E-) subcutaneous oestradiol implants. Blood samples were taken every 12 min for 8 h at weekly intervals, with IGF-1 given at 4 h. In Experiment 1, sheep were fed to maintain live weight (maintenance) and IGF-1 doses tested were 25, 50, 100 and 150 micrograms kg-1 given via the carotid (i.c.). Plasma LH concentrations were 6.2 +/- 0.35 (E-) and 4.2 +/- 0.49 (E+) ng ml-1 pre-IGF-1, were increased after 25 micrograms kg-1 IGF-1 (E-, 15%; E+, 11%) but were either unaltered (E-) or decreased (E+, -16%) after 150 micrograms kg-1; thus, mean LH response was negatively related to IGF-1 dose (E-, b = -0.007, P < 0.01; E+, b = -0.011, P < 0.05). LH pulse frequencies (p.f.) were 4.6 +/- 0.42 (E-) and 3.9 +/- 0.35 (E+) pulses per 4 h pre-IGF-1, were unaltered after 25 micrograms kg-1 IGF-1, but were decreased after 150 micrograms kg-1 (E-, -33%; E+, -51%); thus, p.f. was also negatively related to IGF-1 dose (E-, b = -0.016, P < 0.01; E+, b = -0.019, P > 0.05). LH pulse amplitude and baseline were not significantly altered by IGF-1. Plasma glucose concentrations decreased after 100 and 150 micrograms kg-1 IGF-1 from 3.40 to 2.50 and 2.34 mmol l-1, respectively (SED 0.314, P < 0.001), but were not significantly altered after lower doses. Thus, hypoglycaemia caused LH inhibition after higher doses of IGF-1, which counteracted (E-) or overcame (E+) the stimulatory effects on LH seen after lower doses. In Experiment 2, sheep were fed 50% maintenance; saline vehicle i.c., then IGF-1 doses 25 and 50 micrograms kg-1 given i.c. or i.v. were tested. In E- and E+ sheep, respectively, mean LH pre-IGF-1 was 8.7 +/- 0.97 and 1.9 +/- 0.16 ng ml-1, p.f. was 3.8 +/- 0.44 and 0.8 +/- 0.44 pulses per 4 h, and amplitude was 3.6 +/- 0.49 and 0.4 +/- 0.08 ng ml-1. Saline vehicle had no effect on LH. IGF-1 at both doses and by both administration routes in E- sheep increased mean LH (22-29%, P < 0.001), and in E+ sheep increased mean LH (12-36%, P < 0.001), p.f. (94-219%, P < 0.001) and amplitude (125-803%, P < 0.01). Thus, low doses of peripherally-administered IGF-1 stimulated LH output in sheep, consistent with its putative physiological role as a nutritional modulator of reproduction.