A physiological role for N-methyl-D-aspartic acid and non-N-methyl-D-aspartic acid receptors in pulsatile gonadotropin secretion in the adult female rat

L. Ping, V. B. Mahesh, D. W. Brann

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

The present study was designed to evaluate the physiological role of excitatory amino acids (EAAs) in the pulsatile secretion of LH and FSH. Specific antagonists for N-methyl-D-aspartic acid (NMDA) receptors and kainate/quisqualate (non-NMDA) receptors were used to achieve this aim. Adult female rats (250-280 g), ovariectomized for 2 weeks, were implanted with a cannula in the third ventricle of the brain. One week later, 2-amino-5-phosphono-pentanoic acid (AP-5; 10 μgrams/rat), a specific competitive NMDA receptor antagonist; 6, 7-dinitroquinoxaline-2, 3-dione (DNQX; 30 nM), a selective antagonist of non-NMDA receptors; or the same volume of saline, was injected via the third ventricle to conscious and unrestrained ovariectomized animals. Blood samples were collected from indwelling jugular catheters 20 min before and after injection and at 10-min intervals for 100 min for plasma LH and FSH determinations. The results revealed that the administration of either AP-5 or DNQX significantly suppressed mean as well as trough LH levels. This suppression was accompanied by a suppression of LH pulse frequency and LH pulse amplitude. AP-5 suppressed LH pulse amplitude, through LH levels, and mean LH levels to a greater degree than DNQX. The analysis of FSH pulses showed that AP-5 inhibited mean and trough FSH levels, and this appeared to be achieved by the suppression of FSH pulse amplitude, but not frequency. DNQX, on the other hand, did not significantly alter FSH pulse frequency, pulse amplitude, or trough or mean FSH levels. Taken as a whole, the present study provides evidence that endogenous EAAs, acting through both NMDA and non-NMDA receptors, play an important physiological role in the generation of pulsatile LH secretion in adult female rats. FSH pulse frequency was not significantly affected by the administration of either EAA receptor antagonist, although AP-5 did suppress FSH pulse amplitude and mean and trough FSH levels.

Original languageEnglish (US)
Pages (from-to)113-118
Number of pages6
JournalEndocrinology
Volume135
Issue number1
DOIs
StatePublished - Jul 1994

Fingerprint

D-Aspartic Acid
N-Methylaspartate
Gonadotropins
Excitatory Amino Acids
Third Ventricle
Pentanoic Acids
Quisqualic Acid
Excitatory Amino Acid Antagonists
Indwelling Catheters
Kainic Acid
Glutamate Receptors
Neck
aspartic acid receptor
FG 9041
Injections
Brain

ASJC Scopus subject areas

  • Endocrinology

Cite this

A physiological role for N-methyl-D-aspartic acid and non-N-methyl-D-aspartic acid receptors in pulsatile gonadotropin secretion in the adult female rat. / Ping, L.; Mahesh, V. B.; Brann, D. W.

In: Endocrinology, Vol. 135, No. 1, 07.1994, p. 113-118.

Research output: Contribution to journalArticle

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abstract = "The present study was designed to evaluate the physiological role of excitatory amino acids (EAAs) in the pulsatile secretion of LH and FSH. Specific antagonists for N-methyl-D-aspartic acid (NMDA) receptors and kainate/quisqualate (non-NMDA) receptors were used to achieve this aim. Adult female rats (250-280 g), ovariectomized for 2 weeks, were implanted with a cannula in the third ventricle of the brain. One week later, 2-amino-5-phosphono-pentanoic acid (AP-5; 10 μgrams/rat), a specific competitive NMDA receptor antagonist; 6, 7-dinitroquinoxaline-2, 3-dione (DNQX; 30 nM), a selective antagonist of non-NMDA receptors; or the same volume of saline, was injected via the third ventricle to conscious and unrestrained ovariectomized animals. Blood samples were collected from indwelling jugular catheters 20 min before and after injection and at 10-min intervals for 100 min for plasma LH and FSH determinations. The results revealed that the administration of either AP-5 or DNQX significantly suppressed mean as well as trough LH levels. This suppression was accompanied by a suppression of LH pulse frequency and LH pulse amplitude. AP-5 suppressed LH pulse amplitude, through LH levels, and mean LH levels to a greater degree than DNQX. The analysis of FSH pulses showed that AP-5 inhibited mean and trough FSH levels, and this appeared to be achieved by the suppression of FSH pulse amplitude, but not frequency. DNQX, on the other hand, did not significantly alter FSH pulse frequency, pulse amplitude, or trough or mean FSH levels. Taken as a whole, the present study provides evidence that endogenous EAAs, acting through both NMDA and non-NMDA receptors, play an important physiological role in the generation of pulsatile LH secretion in adult female rats. FSH pulse frequency was not significantly affected by the administration of either EAA receptor antagonist, although AP-5 did suppress FSH pulse amplitude and mean and trough FSH levels.",
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