Recombinant porcine leptin reduces feed intake and stimulates growth hormone secretion in swine.

Two experiments (EXP) were conducted to test the hypothesis that porcine leptin affects GH, insulin-like growth factor-I (IGF-I), insulin, thyroxine (T4) secretion, and feed intake. In EXP I, prepuberal gilts received intracerebroventricular (i.c.v.) leptin injections. Blood was collected every 15 min for 4 hr before and 3 hr after i.c.v. injections of 0.9% saline (S; n = 3), 10 micrograms (n = 4), 50 micrograms (n = 4), or 100 micrograms (n = 4) of leptin in S. Pigs were fed each day at 0800 and 1700 hr over a 2-wk period before the EXP. On the day of the EXP, pigs were fed at 0800 hr and blood sampling started at 0900 h. After the last sample was collected, feeders were placed in all pens. Feed intake was monitored at 4, 20, and 44 hr after feed presentation. In EXP II, pituitary cells from prepuberal gilts were studied in primary culture to determine if leptin affects GH secretion at the level of the pituitary. On Day 4 of culture, 10(5) cells/well were challenged with 10(-12), 10(-10), 10(-8), or 10(-6) M [Ala15]-h growth hormone-releasing factor-(1-29)NH2 (GRF), 10(-14), 10(-13), 10(-12), 10(-11), 10(-10), 10(-9), 10(-8), 10(-7), or 10(-6) M leptin individually or in combinations with 10(-8) and 10(-6) M GRF. Secreted GH was measured at 4 hr after treatment. In EXP I, before injection, serum GH concentrations were similar. Serum GH concentrations increased (P < 0.01) after injection of 10 micrograms (21 +/- 1 ng/ml), 50 micrograms (9 +/- 1 ng/ml), and 100 micrograms (13 +/- 1 ng/ml) of leptin compared with S (1 +/- 2 ng/ml) treated pigs. The GH response to leptin was greater (P < 0.001) in 10 micrograms than 50 or 100 micrograms leptin-treated pigs. By 20 hr the 10, 50, and 100 micrograms doses of leptin reduced feed intake by 53% (P < 0.08), 76%, and 90% (P < 0.05), respectively, compared with S pigs. Serum IGF-1, insulin, T4, glucose, and free fatty acids were unaffected by leptin treatment. In EXP II, relative to control (31 +/- 2 ng/well), 10(-10), 10(-8), and 10(-6) M GRF increased (P < 0.01) GH secretion by 131%, 156%, and 170%, respectively. Only 10(-6) M and 10(-7) M leptin increased (P < 0.01) GH secretion. Addition of 10(-11) and 10(-9) M leptin in combination with 10(-6) M GRF or 10(-11) M leptin in combination with 10(-8) M GRF-suppressed (P < 0.05) GH secretion. These results indicate that leptin modulates GH secretion and, as shown in other species, leptin suppressed feed intake in the pig.