Alpha-fetoprotein protects the developing female mouse brain from masculinization and defeminization by estrogens (Nat Neurosci, 2006, 9:220-226)

報告日期: 2006/05/12
報告時間: 15:10/16:00
報告學生: 林長儀 (英文報告)
講評老師: 蔡美玲
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Alpha-fetoprotein protects the developing female mouse brain from masculinization and defeminization by estrogens

Nat. Neurosci., 8(2005), p346-353

Speaker:Lin, Chang-Yi                      Date/Time:2006/5/12

Commentator:Dr. Tsai, Mei-Ling             Room602

Abstract

In many mammalian species, aggressive tendencies and indiscriminate sexual interests of male are adaptive for male reproductive strategies to help him to compete with other males for mates. But aggressive responses are maladaptive for female reproductive success, that is, defeminization. So for females, testosterone exposure during development might lead to display male behaviors, that is, masculinization. How do females avoid testosterone exposure, especially in mammalian species with high litters where almost every female fetus shares the uterus with brothers? Previous studies suggested that a-fetoprotein (AFP) could controversially either keep out1 or escort2 estrogens derived form the neural aromatization of testosterone into specific neurons and play and important role in brain sexual differentiation3. Here, the authors used Afp-/- female mice to demonstrate the AFP function in brain sexual differentiation. They found that Afp-/- female mice dramatically decreased the number of lordosis responses. And both Afp-/- and Afp+/- female mice increased the mount frequency. Besides sexual behavior, Afp-/- female mice were also affected at the neurochemical level which is sexually dimorphic. However, masculinization and defeminization of Afp-/- female mice were rescued by the inhibition of estrogen production with the aromatase inhibitor, 1,4,6-androstatrience-3,17-dione. These results indicated that prenatal estrogens could masculinize and defeminize the female brain and AFP could protect the female brain from these effects.

References

1.        Baum, M. J. Differentiation of coital behavior in mammals: a comparative analysis. Neurosci Biobehav Rev 3, 265-84 (1979).

2.         Toran-Allerand, C. D. Sex differences in the brain: the relation between structure and function. Proceedings of the 13th International School of Brain Research. Amsterdam, The Netherlands, 22-26 August 1983. Prog Brain Res 61, 1-516 (1984).

3.         Gabant, P. et al. Alpha-fetoprotein, the major fetal serum protein, is not essential for embryonic development but is required for female fertility. Proc Natl Acad Sci U S A 99, 12865-70 (2002).