The Journal of Neurophysiology Vol. 86 No. 5 November 2001, pp. 2374-2380
Copyright ©2001 by the American Physiological Society

Prenatal Exposure of Testosterone Prevents SDN-POA Neurons of Postnatal Male Rats From Apoptosis Through NMDA Receptor

 ¹Department of Physiology, Kaohsiung Medical College, Kaohsiung 807; and  ²School of Nursing, Mei-Ho Institute of Technology, Pingtung 900, Taiwan

Hsu, Hseng-Kuang, Rei-Cheng Yang, Huei-Chuan Shih, Ya-Lun Hsieh, U-Yang Chen, and Chin Hsu. Prenatal Exposure of Testosterone Prevents SDN-POA Neurons of Postnatal Male Rats From Apoptosis Through NMDA Receptor. J. Neurophysiol. 86: 2374-2380, 2001. The role of N-methyl-D-aspartate (NMDA) receptor in mediating the effect of testosterone exposure prenatally on neuronal apoptosis in the sexual dimorphic nucleus of the preoptic area (SDN-POA) of rats was studied. The endogenous testosterone was diminished by prenatal stress (PNS) or simulated by testosterone exposure (TE) to understand the effect of testosterone on NR₁ (a functional subunit protein of NMDA receptor) expression and neuronal apoptosis. To further study whether the testosterone, after being converted into estradiol, modulates NR₁ expression, 4-androstein-4-ol-3,17-dione (ATD; an aromatase inhibitor) was used to block the conversion of estradiol from testosterone. The expressions of the NR₁ mRNA and NR₁ subunit protein were quantified by RT-PCR and western blotting analysis, respectively. In addition, a noncompetitive antagonist of NMDA receptor, MK-801, was used to find out whether blockage of NMDA receptor affects the naturally occurring apoptosis in SDN-POA. The results showed the following. 1) Expression of perinatal NR₁ subunit protein in the central part of the medial preoptic area of male rats was significantly higher than that of females, especially on postnatal days 1 and 3. 2) The testosterone level of male fetuses on embryonic day 18 was significantly higher than that of females, while the testosterone level of TE females or PNS males was similar to that of intact males or intact females, respectively. 3) The apoptotic incidence of intact male rats was significantly less than that of females, and the apoptosis was stimulated by PNS in male or inhibited by TE in female. 4) The expression of NR₁ subunit protein could be inhibited by PNS or ATD-treatment in male, while stimulated by TE in female. 5) NR₁ mRNA showed no significant difference among intact male, PNS male, ATD-treated male, TE female and intact female rats. 6) The low apoptotic incidence of male rats was significantly increased when NMDA receptor was blocked by MK-801. These results suggest that testosterone, after being converted to estradiol, may prevent the SDN-POA neurons of male rats from apoptosis through enhancing the expression of NR₁ at the posttranscriptional level.