ASPARTATE AND GLUTAMATE MODULATION OF GROWTH-HORMONE SECRETION IN THEPIG - POSSIBLE SITE OF ACTION

The influence of excitatory amino acids (EAA) on growth hormone (GH) s ecretion and thr possible site of action was investigated in the pig. In Experiment (Exp) I three replicates were conducted with 30 prepuber al gilts, 130 d of age and averaging 70.6 +/- 1.3 kg body weight (BW). Six gilts each received intravenously (iv) 0, 50, 100, or 150 mg/kg B W of aspartate (ASP) or glutamate (GLU) in saline. Blood samples were collected every 15 min for 2 hr before and 3 hr after treatment. In Ex p II, mature ovariectomized gilts (163 +/- 10 kg BW) that had been imm unized against growth hormone releasing factor (GRF) conjugated to hum an serum albumin (GRFi; n = 4) or against human serum albumin alone (H SAi; n = 5) received 150 mg/kg BW ASP or GLU iv in a 2 x 2 factorial a rrangement of treatments, which was then repeated in a crossover desig n. One week later, all animals received 10 mg/kg N-methyl-D,L-aspartat e (NMA; EAA agonist) in saline iv. Blood samples were collected as des cribed above. In Exp III, cultures of anterior pituitary cells from ma rket-weight (averaging 105 kg BW) gilts were studied. On Day 4 of cult ure, cells (10(5) seeded/well) were challenged with 10(-8), 10(-6), or 10(-4) M ASP or GLU, 10(-6) M [Ala(15)]-human GRF (1-29)-NH2, or the EAA antagonist, 2-amino-5-phosphonopentanoic acid (10(-4) M; AP5), alo ne or in combination with ASP or GLU. In Exp I, all doses of ASP and t he 100- and 150-mg doses of GLU increased (P < 0.05) GH secretion when compared with Time 0. However, serum GH concentrations were higher (P < 0.01) after 150 mg/kg of ASP when compared with those after 150 mg/ kg of GLU. In Exp II, serum GH concentrations increased (P < 0.05) in HSAi but not in GRFi pigs (averaging 1.2 +/- 0.2 ng/ml before and 8.2 +/- 0.7, 6.3 +/- 0.5, and 9.2 +/- 0.5 ng/ml by 15 min after ASP, GLU, and NMA, respectively). In Exp III, relative to controls (40 +/- 6 ng/ ml), GH increased (P < 0.05) 1.6-, 1.9-, and 1.9-fold and 1.7-, 1.8-, and 2.0-fold after 10(-8), 10(-6), and 10(-4) M ASP and GLU, respectiv ely. The EAA receptor antagonist AP5 failed to prevent the GH response to ASP or GLU, except for 10(-8) M ASP. In summary, ASP is a more pot ent secretagogue of GH secretion than is GLU in vivo, whereas each is equipotent in vitro. Because no stimulation of GH by EAA was observed in GRFi pigs and no specific dose-response effect of EAA was found in vitro, it may be concluded that modulation by EAA is mediated primaril y at the level of the hypothalamus or higher brain centers.