DOMESTIC ANIMAL ENDOCRINOLOGY Vol. 9(2):105-114,1992 ELICITATION OF RELEASE OF LUTEINIZlNG HORMONE BY N-METHYL -D,L-ASPARTIC ACID DURING THREE PARADIGMS OF SUPPRESSED SECRETION OF LUTEINIZlNG HORMONE IN THE FEMALE PIG L.A.C. Sesti and J.H. Britt 1 Department of Animal Science North Carolina State University Raleigh, North Carolina, 27695-7621 Received May 7, 1991 ABSTRACT Two experiments were conducted to determine the minimal effective dose during lactation and site of action of N-methyl-d,l-aspartic acid (NMA) for elicitation of release of luteinizing hormone (LH) in female pigs. In the first experiment, three doses of NMA were given to lactating primipa- rous sows in which endogenous LH was suppressed by suckling of litters. In the second experiment, ovariectomized gilts were pretreated with estradiol benzoate or porcine antisera against GnRH to suppress LH and then given NMA to determine if it elicited secretion of LH directly at the anterior pituitary or through release of GnRH. In experiment I, 3 lactating sows (17 + 1.5 d postpartum) were each given three doses of NMA (1.5, 3.0 and 5.0 mg/kg body weight [BW]; IV) on 3 consecutive days in a Latin Square design. Blood samples were collected every 10 min from -1 to 1 hr from in- jection of NMA. NMA at 1.5 and 3.0 mg/kg did not affect (p>.5) secretion of LH; however, 5 mg NMA/kg elicited a 114% increase (p<.001) in circulating levels of LH during 1 hr after treatment. In experiment 2, 8 ovariectomized gilts were given either estradiol benzoate (EB; 10 lag/kg BW; IM n = 4) to suppress release of GnRH or porcine antiserum against GnRH (GnRH-Ab; titer 1:8,000; 1 ml/kg BW; IV; n = 4) to neutralize endogenous GnRH. Gilts infused with GnRH-Ab were given a second dose of antiserum 24 hr after the first. Gilts were then given NMA (10 mg/kg BW; IV) 33 hr after EB or initial GnRH-Ab. Blood samples were drawn every 6 hr from -12 to 24 hr from EB or GnRH-Ab treatments, and every 10 min from -2 to 2 hr from NMA. Serum LH declined (p<.001) after EB (from 1.87 + .2 ng/ml at 12 hr before EB to 0.46 + .02 ng/mi during 24 hr after EB) and GnRH-Ab (from 1.97 +. 1 to 0.59 + .02 ng/ml). In gilts treated with EB, the area under the curve (AUC) for the LH response (ngml-~min) 1 hr after NMA (38.7 + 3) was significantly greater (p<.01) than the ! hr prior to NMA (21.3 + 1.5). Treatment with NMA had no effect (p>.5) on secretion of LH in gilts infused with GnRH-Ab. These results demonstrate that as little as 5 mg NMA/kg evokes LH secretion in female pigs and that NMA elicits LH release via stimulation of release of GnRH. INTRODUCTION Excitatory amino acids (EAA) such as 1-aspartic and 1-glutamic acid play important roles in synaptic transmission in the central nervous system (1). Neuronal communication via EAA represents at least 50% of all synaptic activity in the mammalian brain, and practically every neuron receives information coded through the release of an EAA (2). Studies have demonstrated that EAA and their potent agonist N-methyl-d,l-aspartic acid (NMA) enhance secretion of luteinizing hormone (LH) in the rat (3, 4, 5, 6,), monkey (7, 8) and Syrian ham- ster (9). Recently, it has been reported that NMA also can enhance LH release in estrogen- treated, ovariectomized ewes (10) and seasonally anestrous ewes (11), but not in castrated rams (12) and ovariectomized gilts (10). The mechanism by which NMA stimulates secre- tion of LH is apparently through the release of gonadotropin-releasing hormone (GnRH), because NMA has been reported to evoke GnRH release in explants of hypothalamus (13, 14) without affecting basal or GnRH-induced release of LH from pituitary glands in vitro (15). Moreover, pretreatment of monkeys with a potent GnRH receptor antagonist totally Copyright © 1992 Butterworth-Heinemann 105 0739-7240/92/$3.00