Localization of aromatase and 5 alpha-reductase to neuronal and non-neuronal cells in the fetal rat hypothalamus.
Experiments were designed to identify the neural cell type(s) responsible for the aromatization and 5 alpha-reduction of androgens in the rat hypothalamus. Primary cultures of fetal rat hypothalamic cells, which had enhanced neuronal morphology, were treated at various times after plating with kainic acid (KA), a neurotoxic agent which selectively destroys neuronal cells. Neuronal morphology was disrupted in a time (0-6 days)- and dose (10(-4)-10(-2) M)-dependent fashion after KA treatment, with no apparent change in the appearance of the flattened, underlying non-neuronal cells. KA treatment for 4 days decreased aromatization by 94% in a dose-dependent fashion (10(-4)-10(-2) M KA), while 5 alpha-reduction declined by no more than 25%. A 6-day time course with 10(-3) M KA showed a dramatic decline in aromatization and no alteration in 5 alpha-reduction. In control experiments, substance P, a neuronal peptide, declined after KA treatment while the activity of glutamine synthetase, a glial enzyme, did not change. We conclude from these results that aromatase is localized primarily to neuronal cells in the hypothalamus while 5 alpha-reductase is confined primarily to non-neuronal cells.
Canick
J A
JA
Vaccaro
D E
DE
Livingston
E M
EM
Leeman
S E
SE
Ryan
K J
KJ
Fox
T O
TO
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism*; D000818:Animals; D001141:Aromatase / Q000378:metabolism*; D046508:Culture Techniques; D005333:Fetus; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D007031:Hypothalamus / Q000201:enzymology*; D007608:Kainic Acid / Q000494:pharmacology; D009457:Neuroglia / Q000201:enzymology; D009474:Neurons / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D013373:Substance P / Q000032:analysis
D013373:Substance P; D001141:Aromatase; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; D005974:Glutamate-Ammonia Ligase; D007608:Kainic Acid