Effects of androgen on the expression of brain aromatase cytopigment and nerve growth factor in neonatal rats with hypoxic-ischemic brain damage.
OBJECTIVE
To study the effects of androgen on the expression of aromatase cytopigment P450 (AROM) and nerve growth factor (NGF) in the brain and brain ultrastructure in neonatal rats with hypoxic-ischemic brain damage (HIBD) in order to investigate the mechanism underlying the protective effect of androgen against HIBD.


METHODS
Ninety-six seven-day-old Sprague-Dawley rats were randomly divided into three groups: sham-operation, HIBD and androgen treatment (n=32 each). HIBD was induced by the ligation of left common carotid artery and hypoxia exposure. The rats in the androgen treatment and the HIBD groups were injected intraperitoneally with testosterone propionate (25 mg/kg) and arachis oil respectively immediately after hypoxia-ischemia (HI). After 24 and 72 hrs and 7 and 10 days of HI, AROM and NGF expression in the cortex and the hippocampus was detected with the immunohistochemical method. The ultrastructural changes of neurons in the cortex and the hippocampus were observed under a transmission electron microscope.


RESULTS
Nerve cells of the HIBD group showed obvious injuries including cell organ decreasing, cellularoedema, nuclear swelling, chromatic agglutination, mitochondria decreasing and swelling, as well as an increase in apoptotic cells. Compared with the HIBD group, the nerve cells in the androgen treatment group had integrated nuclear membrane, well-distributed chromatin and abundant cell organs, and less cell apoptosis and increased axon regeneration. There was a positive expression of NGF and AROM in the brain cortex and the hippocampus in the HIBD group 24 hrs after HI. The expression of NGF and AROM increased significantly 72 hrs after HI, peaked 7 days after HI and then began to decrease but remained at a higher level than that in the sham-operation group 10 days after HI. The NGF and AROM expression in the cortex and the hippocampus in the androgen treatment group was significantly higher than that in the sham-operation and the HIBD groups 72 hrs, and 7 and 10 days after HI.


CONCLUSIONS
Androgen treatment can promote axon regeneration and morphous recovery of neurons and decrease neural apoptosis in neonatal rats with HIBD. The neuroprotection of androgen is produced possibly through an increase in the expression of NGF and AROM in the brain.
Li
Zhan-Kui
ZK
Department of Neonatology, Maternal and Child Health Care Hospital of Shanxi Province, Xi'an 710003, China. lzk@mail.xjtu.edu.cn
Shen
Ling
L
Ke
Hua
H
Li
Fei
F
Ni
Li-Ming
LM
Li
Qing-Hong
QH
D000728:Androgens / Q000627:therapeutic use*; D000818:Animals; D000831:Animals, Newborn; D001141:Aromatase / Q000032:analysis*; D001921:Brain / Q000201:enzymology*; D005260:Female; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D020932:Nerve Growth Factor / Q000032:analysis*; D009474:Neurons / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley
D000728:Androgens; D020932:Nerve Growth Factor; D001141:Aromatase