Acute Elevations of Serum Luteinizing Hormone Induced by Kainic Acid, N-Methyl Aspartic Acid or Homocysteic Acid

Abstract

It has been previously demonstrated that glutamate (GLU), a neuroexcitatory amino acid which destroys neurons in the arcuate nucleus of the hypothalamus (AH) when administered in high subcutaneous (s.c.) doses to rodents, induces an acute elevation of serum luteinizing hormone (LH) when administered in non-toxic doses, i.e., doses lower than those required to damage AH neurons. It is postulated that a neuroexcitatory mechanism (excitation of AH neurons) underlies the acute rise in serum LH induced by GLU. To explore this hypothesis, we administered several potent excitatory analogs of GLU – kainic acid (KA), N-methyl-aspartic acid (NMA) and homocysteic acid (HCA) -in low doses to 25-day-old male rats and found that each analog mimics GLU in producing acute elevations of serum LH. The lowest doses effective (LED) in inducing significant elevations in LH were: 0.03 μ M/g KA, 0.1 μ M/g NMA and 0.3 μ M/gHCA. Thus, the order of potencies (KA > NMA > HCA) for inducing LH elevations was the same as has been shown for either the neuroexcitatory or neurotoxic activities of these compounds. With the possible exception of KA, each compound induced LH elevations at 1/3–1/4 the lowest effective toxic doses (LETD). It is tentatively concluded that these potent neuroexcitatory analogs of GLU readily penetrate AH from blood and stimulate firing of AH neurons which triggers discharge of luteinizing hormone-releasing hormone (LH-RH) into portal blood to give rise to pituitary output of LH. This interpretation, if corroborated, suggests that these compounds may be useful tools for studying mechanisms of neuro-endocrine regulation.