Luteinizing Hormone Responses to N‐Methyl‐D,L‐Aspartate During a Photoperiodically‐lnduced Reproductive Cycle in the Ram

Abstract

Aspartate and glutamate represent a major class of excitatory amino-acid neurotransmitters in the vertebrate brain, and stimulation of glutaminergic receptors by the specific agonist N-methyl-D,L-aspartate (NMDA) induces luteinizing hormone-releasing hormone (LHRH) and LH secretion. In this study, we used NMDA as a probe to investigate the hypothalamic regulation of LH secretion at different stages of a reproductive cycle in Soay rams induced by exposure to alternating 16-week periods of long and short days. NMDA (20 mg/kg) injected intravenously caused an acute increase in blood plasma concentrations of LH, with a significant increase within 2 to 4 min, and peak levels within 20 min. The magnitude of the response changed markedly during the cycle; it was greatest in the sexually inactive phase under long days (with a linear dose-response over the range 1 to 20 mgikg NMDA) and least in the sexually active phase under short days (only 20 mg/kg NMDA produced a small response). Pituitary responsiveness to a standard dose of LHRH (5.3 ng/kg iv) varied only slightly at the different stages and could not account for the observed changes in the LH response to NMDA. There were the expected changes in the endogenous pattern of LH secretion during the cycle, with high frequency LH pulses occurring during the sexually active phase. There was an inverse relationship between the frequency of LH pulses and the LH response to NMDA. Pretreatment of rams with an LHRH antagonist (36 pg/kg iv; Syntex, RS18286) totally blocked the LH response to both NMDA and LHRH, while in a separate study, treatment with dexamethasone (synthetic glucocorticoid, 133.4 pglkg iv) partially blocked the LH responses. The overall results indicate that NMDA stimulates LHRH secretion in the ram and the response is independent of the activation of the hypothalamo-pituitary-adrenal axis. The variation in the LH response during the reproductive cycle may reflect changes in the releasable stores of LHRH in the median eminence. These appear to be depleted in the sexually active phase, when LHRH is secreted in pulses at high frequency. The variation in the response to NMDA may also reflect changes in release of endogenous excitatory amino-acids, which act via NMDA receptors to form part of the physiological regulation of the reproductive cycle in the ram.The dicarboxylic amino-acids aspartate and glutamate represent a major class of excitatory neurotransmitters in the vertebrate brain ( I ) . These amino-acids have excitatory effects through at least three classes of receptors of which the N-methyl-D,Laspartate (NMDA) receptor class is best characterized, and these receptors are apparently involved in the neural control of reproduction (2). Studies in the rat have shown that the administration of NMDA causes the release of luteinizing hormone (LH) from the anterior pituitary gland by inducing the secretion of LHreleasing hormone (LHRH) from the hypothalamus (3, 4), and there is evidence that both NMDA and non-NMDA excitatory amino-acid receptors are in...

The effect of nutrition on the neural mechanisms potentially involved in melatonin-stimulated LH secretion in female Mediterranean goats

“…The response to the naloxone injection before melatonin implantation suggests that endogenous opioids are not involved in the inhibition of LH secretion by long days since no response was observed, as previously reported (Zarazaga et al 2011a). The injection of NMDA increased the LH concentration in both the H and L groups, indicating that nutritional level does not modify the response to EAA and that this mechanism is involved in LH secretion during the period of its photo-induced inhibition (Lincoln & Wu 1991).…”

“…In support of this, the administration of NMDA, a glutamatergic receptor agonist, acutely stimulates LH secretion (Viguié et al 1995b). This stimulatory effect is larger during the period of photoinhibition of LH secretion than during the photostimulation, suggesting that EAA are involved in the photoperiodic regulation of LH secretion (Lincoln & Wu 1991). In bucks, the stimulatory effect of NMDA on LH secretion is more pronounced when subjected to long days than short days (Gazal et al 2002).…”

“…Acting through N-methyl-D,L-aspartate (NMDA) receptors, in sheep, these amino acids modulate the secretion of LH (Estienne et al 1990, Lincoln & Wu 1991. In support of this, the administration of NMDA, a glutamatergic receptor agonist, acutely stimulates LH secretion (Viguié et al 1995b).…”

The neuroendocrine timing of puberty

“…For example, treatment with the glutamate agonist N-methyl-D-aspartate (NMDA) rapidly induces LH secretion in a wide range of prepubertal species including primates, sheep and rodents (Plant et al 1989, Ebling & Cronin 1998. Concurrent treatment with GnRH receptor antagonists blocks the effect of NMDA indicating a likely action on GnRH release rather than an action directly upon the pituitary gland (Lincoln & Wu 1991). Moreover, in adult sheep, NMDA has been shown to increase GnRH concentrations in the portal capillaries draining the median eminence (Viguie et al 1995).…”

Melatonin and the seasonal control of reproduction

“…This inhibitory effect of serotonin is mediated by 5-HT2 A receptors [34] and interestingly a photoperiod-induced change in the density of 5-HT2 A receptors in the ventrolateral posterior hypothalamus was described [35,54]. 4 [28,42,70]. Also, in male hamsters, the inhibitory effect of short days on testicular activity can be blocked by chronic treatment with NMDA [66].…”