Alpha-fetoprotein protects the developing female mouse brain from masculinization and defeminization by estrogens


Autoria(s): Bakker, Julie; De Mees, Christelle; Douhard, Quentin; Balthazart, Jacques; Gabant, Philippe; Szpirer, Josiane; Szpirer, Claude
Data(s)

01/02/2006

Resumo

Two clearly opposing views exist on the function of alpha-fetoprotein (AFP), a fetal plasma protein that binds estrogens with high affinity, in the sexual differentiation of the rodent brain. AFP has been proposed to either prevent the entry of estrogens or to actively transport estrogens into the developing female brain. The availability of Afp mutant mice (Afp-/-) now finally allows us to resolve this longstanding controversy concerning the role of AFP in brain sexual differentiation, and thus to determine whether prenatal estrogens contribute to the development of the female brain. Here we show that the brain and behavior of female Afp-/- mice were masculinized and defeminized. However, when estrogen production was blocked by embryonic treatment with the aromatase inhibitor 1,4,6-androstatriene-3,17- dione, the feminine phenotype of these mice was rescued. These results clearly demonstrate that prenatal estrogens masculinize and defeminize the brain and that AFP protects the female brain from these effects of estrogens. © 2006 Nature Publishing Group.

SCOPUS: ar.j

info:eu-repo/semantics/published

Formato

No full-text files

Identificador

uri/info:doi/10.1038/nn1624

uri/info:pii/NN1624

uri/info:pmid/16388309

uri/info:pmid/16687103

local/VX-005538

http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/109975

Idioma(s)

en

Fonte

Nature neuroscience, 9 (2

Palavras-Chave #Biologie moléculaire #Animals #Aromatase Inhibitors -- pharmacology #Brain -- drug effects -- embryology #Estrogens -- metabolism #Female #Immunohistochemistry #Mice #Mice, Mutant Strains #Sex Differentiation -- drug effects -- physiology #Tyrosine 3-Monooxygenase -- biosynthesis #Vasopressins -- biosynthesis #alpha-Fetoproteins -- drug effects -- metabolism
Tipo

info:eu-repo/semantics/article

info:ulb-repo/semantics/articlePeerReview

info:ulb-repo/semantics/openurl/article