Localization of aromatase and 5α-reductase to neuronal and non-neuronal cells in the fetal rat hypothalamus

Abstract

Experiments were designed to identify the neural cell type(s) responsible for the aromatization and 5α-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 5α-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 5α-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 5α-reductase is confined primarily to non-neuronal cells.