Altered luteinizing hormone and prolactin responses to excitatory amino acids during lactation

Rula Abbud, M (Susan) Smith

Research output: Contribution to journalArticle

Abstract

We have used excitatory amino acids as tools to elucidate changes in hypothalamic function associated with lactation, focusing on the regulation of luteinizing hormone (LH) and prolactin secretion. In these studies, we have compared the responsiveness to NMA (N-methyl- D, L-aspartate), an agonist for the N-methyl-D-aspartate (NMDA) receptor, with that of kai- nate, an agonist for another type of glutamate receptor, the kainate receptor. To address the issue of the permeability of the blood-brain barrier to either NMA or kainate, systemic and central administration of the drugs were compared. Four injections of either drug were administered at 10-min intervals to cycling or lactating rats suckling 8 pups. All of these treatment significantly stimulated LH secretion in cycling rats. However, neither systemic injections of NMA (40 mg/kg) or kainate (2.5-3.5 mg/kg), nor third-ventricular administration of NMA (2 μg/2 μl) or kainate (0.2-0.3 μg/2 μl) stimulated LH secretion during lactation. In contrast, LH responses to NMA were observed in lactating animals suckling 2 pups. These data demonstrate that the intensity of the suckling stimulus determines the degree of gonadotropin-releasing hormone (GnRH) neuronal inhibition during lactation. Recovery of the LH response to NMA in animals suckling 8 pups was not observed after treatment with RU 486 to block the effects of progesterone. Thus, the elevated levels of progesterone during lactation do not appear to play a role in inhibiting GnRH neuronal responsiveness. Removal of the 8-pup suckling stimulus for 24 h also did not restore the LH response to NMA, However, treatment with RU 486 and removal of the suckling stimulus for 24 h did restore LH responses to NMA, suggesting that progesterone may play a role in prolonging the recovery of GnRH neuronal responsiveness. The prolactin responses to NMA and kainate changed with the reproductive state of the animal and the site of administration. Central injections of either drug stimulated prolactin release in both cycling and lactating animals. In contrast, whereas systemic administration of NMA stimulated prolactin secretion in cycling animals, kainate had no effect. In the lactating animals, systemic administration of either drug inhibited prolactin secretion. Thus, the difference in the prolactin responses to systemic administration of the drugs may not only be due to a difference in the distribution of kainate and NMDA receptors but also to the steady state level of activity of the prolactin-releasing and -inhibiting factors which is determined by the reproductive state of the animal. In conclusion, lactation alters the responsiveness of several neuronal populations to stimulation by excitatory amino acids. It appears to inhibit GnRH neuronal reponsiveness, as well as to alter the responsiveness of other neurons involved in the regulation of prolactin secretion.

Original languageEnglish (US)
Pages (from-to)454-464
Number of pages11
JournalNeuroendocrinology
Volume58
Issue number4
DOIs
StatePublished - 1993
Externally publishedYes

Fingerprint

Excitatory Amino Acids
Luteinizing Hormone
Lactation
Prolactin
Kainic Acid
Gonadotropin-Releasing Hormone
Suckling Animals
Progesterone
Mifepristone
Pharmaceutical Preparations
N-Methyl-D-Aspartate Receptors
Injections
Kainic Acid Receptors
Glutamate Receptors
N-Methylaspartate
Blood-Brain Barrier
Aspartic Acid
Permeability
Therapeutics
Neurons

Keywords

  • Kainate
  • L-aspartate
  • Lactation
  • Luteinizing hormone
  • N-methy1-D
  • Prolactin

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Cellular and Molecular Neuroscience
  • Endocrine and Autonomic Systems
  • Neuroscience(all)

Cite this

Altered luteinizing hormone and prolactin responses to excitatory amino acids during lactation. / Abbud, Rula; Smith, M (Susan).

In: Neuroendocrinology, Vol. 58, No. 4, 1993, p. 454-464.

Research output: Contribution to journalArticle

Abbud, Rula ; Smith, M (Susan). / Altered luteinizing hormone and prolactin responses to excitatory amino acids during lactation. In: Neuroendocrinology. 1993 ; Vol. 58, No. 4. pp. 454-464.
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