N-Methyl-D, L-aspartate modulation of luteinizing hormone and growth hormone secretion from pig pituitary cells in culture

Administration of n-methyl-d, l-aspartate (NMA) to pigs in vivo increased GH and suppressed LH secretion. Cultures of anterior pituitary cells from pigs in the follicular phase (FOL; n=3) and luteal phase (LUT; n=3) of the estrous cycle, and ovariectomized (OVX; n=10) pigs were treated with NMA (10-4, 10-6 or 10-8 M) or the NMA antagonist, 2-amino-5-phosphonopentanoic acid (AP5; 10-4, 10-6 or 10-8 M), to determine if NMA affects the pituitary directly. Secreted LH and GH were measured at 4 h after treatment. Basal LH and GH secretion (control; C) were 1.1 ± 0.6, 4.4 ±2.1 and 5.6 ±1.3 ng/well and 5.2 ± 1.2, 7.5 ± 1.2 and 5.2 ± 1.7 ng/well for FOL, LUT and OVX, respectively. Relative to C, 10-4 M NMA increased (P<0.001) LH secretion 2.4-, 2.2- and 5.1-fold in FOL, LUT and OVX cultures, respectively. The effect of 10-4 M NMA was inhibited by 10-4 M AP5 (P<0.05) in FOL cultures, but not in OVX cultures. GnRH increased P<0.001) LH levels 3.1-, 2.3- and 3.8-fold in FOL, LUT and OVX cultures, respectively. Relative to C, 10-4, 10-6 and 10-8 M NMA increased (P<0.03) GH secretion 1.5- and 2.3-fold in LUT and 1.7-, 2.3- 2.0-fold in OVX cultures, respectively. AP5 alone or in combination with NMA failed to alter basal GH secretion. Growth hormone releasing factor (GRF) increased (P<0.03) GH secretion 1.9-, 2.5- and 2.6-fold in FOL, LUT and OVX cultures, respectively. Therefore, excitatory amino acids modulate LH and GH secretion directly at the pituitary, while this was not apparent in FOL cultures for GH.