RECOMBINANT PORCINE LEPTIN REDUCES FEED-INTAKE AND STIMULATES GROWTH-HORMONE SECRETION IN SWINE

Two experiments (EXP) were conducted to test the hypothesis that porci ne leptin affects GH, insulin-like growth factor-I (IGF-I), insulin, t hyroxine (T-4,) secretion, and feed intake. In EXP I, prepuberal gilts received intracerebroventricular (ICV) leptin injections. Blood was c ollected every 15 min for 4 hr before and 3 hr after ICV injections of 0.9% saline (S; n = 3), 10 mu g (n = 4), 50 mu g (it = 4), or 100 mu g (n = 4) of leptin in S. Pigs were fed each day at 0800 and 1700 hr o ver 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 sampl e was collected, feeders were placed in all pens. Feed intake was moni tored at 4, 20, and 44 hr after feed presentation. In EXP II, pituitar y cells from prepuberal gilts were studied in primary culture to deter mine 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(-1 0), 10(-8), or 10(-6) M [Ala(15)]-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 treatm ent. In EXP I, before injection, serum GH concentrations were similar. Serum GH concentrations increased (P < 0.01) after injection of 10 mu g (21 +/- ng/ml), 50 mu g (9 +/- 1 ng/ml), and 100 mu g (13 +/- 1 ng/ ml) of leptin compared with S (1 +/-: 2 ng/ml) treated pigs. The GH re sponse to leptin was greater (P < 0.001) in 10 mu g than 50 or 100 mu g leptin-treated pigs. By 20 hr the 10, 50, and 100 mu g doses of lept in reduced feed intake by 53% (P < 0.08), 76%, and 90% (P < 0.05), res pectively, compared with S pigs. Serum IGF-I, insulin, T-4, glucose, a nd free fatty acids were unaffected by leptin treatment. In EXP II, re lative to control (31 +/- 2 ng/well), 10(-10), 10(-8), and 10(-6) M GR F increased (P < 0.01) GH secretion by 131%, 156%, and 170%, respectiv ely. Only 10(-6) M and 10(-7) M leptin increased (P < 0.01) GH secreti on. 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 i ntake in the pig. (C) Elsevier Science Inc. 1998.