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 μg 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 μg kg−1 IGF-1 (E−, 15%; E+, 11%) but were either unaltered (E−) or decreased (E+, -16%) after 150 μg 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 μg kg−1 IGF-1, but were decreased after 150 μg 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 μg 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 μg 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.