Sex-specific aromatization of testosterone in mouse hypothalamic neurons.
Conversion of androgens to oestrogens by neural aromatase during brain development appears to be a prerequisite for sexual differentiation of the mammalian central nervous system. In order to investigate the pre- and perinatal patterns of testosterone (T) aromatization in the male and female mouse brain, aromatase activity (AA) was measured in hypothalamic and cerebral homogenates of embryonic day (ED) 17 fetuses and neonates using an in vitro 3H2O product formation microassay. In addition, AA was examined in gender-specific neuronal cell cultures prepared from ED 15 mouse cerebral hemisphere and hypothalamus at 3 and 6 days in vitro (DIV), and this was compared with enzyme activities in homogenates. The aromatase has also been evaluated in glial-enriched cultures from ED 20 mouse hypothalamus and cortex as well as in ED 15 cultures treated with the neurotoxin kainic acid in order to localize AA to neurons and/or glial cells. Significant sex differences in AA were observed in hypothalamic tissue homogenates as early as ED 17, becoming even more distinct in neonates, AA being always higher in males compared to females. Similar AA was also found in cells from both sexes from cultured ED 15 hypothalamus after 3 DIV. However, significantly higher AA was observed after 6 DIV in ED 15 male hypothalamic cultures compared to female. ED 20 glial-enriched hypothalamic cultures (purity > 95%) from both brain regions exhibited very low AA after 6 DIV, and no sex differences were found.(ABSTRACT TRUNCATED AT 250 WORDS)
Beyer
C
C
AFRC BABRAHAM Institute, MRC Neuroendocrine Development and Behaviour Group, Cambridge, UK.
Wozniak
A
A
Hutchison
J B
JB
D000818:Animals; D000831:Animals, Newborn; D001141:Aromatase / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D007031:Hypothalamus / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D007150:Immunohistochemistry; D007700:Kinetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000201:enzymology / Q000378:metabolism*; D012727:Sex Characteristics; D013739:Testosterone / Q000378:metabolism*
D013739:Testosterone; D001141:Aromatase