Blockage of N-methyl-D-aspartate receptors decreases testosterone levels and enhances postnatal neuronal apoptosis in the preoptic area of male rats

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#animals #animals-newborn #apoptosis #child #dizocilpine-maleate

Blockage of N-methyl-D-aspartate receptors decreases testosterone levels and enhances postnatal neuronal apoptosis in the preoptic area of male rats

Hsu et al., 2000 | Neuroendocrinology | Other

Citation

Hsu C, Hsieh Y L, ... Hsu H K. Blockage of N-methyl-D-aspartate receptors decreases testosterone levels and enhances postnatal neuronal apoptosis in the preoptic area of male rats. Neuroendocrinology. 2000-May;71(5):301-7

Abstract

Sexual dimorphism has been found in the preoptic area of the hypothalamus (POA), a major site of glutamate actions via N-methyl-D-aspartate (NMDA) receptors. The sexually dimorphic nucleus of the preoptic area (SDN-POA) of male rats exhibits about seven-fold greater nuclear volume than that of females. A naturally occurring neonatal neuronal apoptosis, that can be prevented by testosterone, may contribute to this sexual difference in SDN-POA nuclear volume. Since activation of NMDA receptors in the POA induces GnRH secretion, it may be involved in both elevation of serum testosterone and prevention of neuronal death in the SDN-POA. In the present study, protein expression of NMDA receptors in the POA of male and female fetuses was quantified on the day preceding the fetal testosterone peak (embryonic day 16; ED 16). Rats were then distributed in four groups: (1) untreated males, (2) untreated females, (3) males pretreated with MK-801 (a noncompetitive NMDA receptor antagonist), and (4) females pretreated with MK-801. Serum levels of testosterone were estimated on the afternoon of ED 18. Expression of Bcl-2 and Bax, as well as neuronal apoptosis in SDN-POA, were observed on postnatal day 8. The results showed that (1) expression of NMDA receptors in the POA of male fetuses was higher than that of females on ED 16; (2) levels of testosterone were lower in MK-801 pretreated male fetuses than in intact males on ED 18; (3) expression of Bcl-2 in the POA of MK-801 pretreated male rats was significantly less than that of control males; (4) the apoptotic incidence in the SDN-POA of MK-801 pretreated male rats was significantly greater than in control males, while there was no significant difference in apoptotic incidence in the SDN-POA between MK-801 pretreated and intact females. These results suggest that the NMDA receptor is highly expressed in prenatal male fetuses, and that it might play an important role in the elevation of testosterone levels. Moreover, activation of NMDA receptors may protect SDN-POA neurons from naturally occurring neuronal death, by modulating testosterone and/or Bcl-2 expression.

Key Findings

Moreover, activation of NMDA receptors may protect SDN-POA neurons from naturally occurring neuronal death, by modulating testosterone and/or Bcl-2 expression.

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population See abstract
Sample Size See abstract
Age Range See abstract
Condition See abstract

MeSH Terms

  • Animals
  • Animals, Newborn
  • Apoptosis
  • Child
  • Dizocilpine Maleate
  • Embryonic and Fetal Development
  • Female
  • Fetus
  • Gestational Age
  • Humans
  • Male
  • Neurons
  • Preoptic Area
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Rats
  • Rats, Long-Evans
  • Receptors, N-Methyl-D-Aspartate
  • Sex Characteristics
  • Testosterone
  • bcl-2-Associated X Protein

Evidence Classification

  • Level: Other
  • Publication Types: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.
  • Vertical: d-aspartic-acid

Provenance

  • PMID: 10859492
  • DOI: (not available)
  • PMCID: Not in PMC
  • Verified: 2026-04-12 via PubMed E-utilities API

Source extracted via PubMed E-utilities API on 2026-04-12