Developmental Expression and Regulation of Aromatase– and 5α‐Reductase Type 1 mRNA in the Male and Female Mouse Hypothalamus
pmid: 9630396
Developmental Expression and Regulation of Aromatase– and 5α‐Reductase Type 1 mRNA in the Male and Female Mouse Hypothalamus
Androgen metabolites synthesized by neural aromatase and 5α–reductase are implicated in many aspects of mammalian brain development and, in particular, in the masculinization of distinct central nervous system structures and brain functions. The present study was designed to determine (1) the developmental profile of aromatase‐ and 5α–reductase type I mRNA expression in the mouse hypothalamus and (2) to relate ontogenetic sex differences in aromatase activity which have been described in the past to sex‐specific aromatase gene expression. In addition, we analysed the effect of androgens on the perinatal regulation of hypothalamic aromatase and 5α–reductase type I mRNA expression. By applying semiquantitative reverse transcription‐polymerase chain reaction analysis, we found hypothalamic aromatase mRNA expression to be developmentally regulated and to display sex differences at birth and on postnatal day 15 with higher mRNA levels in males. Newborn males and females, which were treated in utero with the androgen receptor antagonist cyproterone actetate, exhibited significantly reduced aromatase mRNA levels compared with untreated controls. In contrast to aromatase, expression levels of hypothalamic 5α–reductase mRNA did not reveal a clear‐cut developmental profile or sex differences, and no regulatory role for androgens in controlling 5α–reductase mRNA expression was found. In conclusion, these results demonstrate perinatal sex differences in hypothalamic aromatase‐ but not 5α–reductase gene expression and suggest that sex differences in perinatal aromatase activity are reflected by corresponding differences in mRNA levels. Androgens are found to control brain estrogen formation pretranslationally at the level of aromatase gene expression. Our findings imply that sex differences in androgen availability and responsiveness are important regulatory factors for aromatase expression in the developing male hypothalamus.
- University of Ulm Germany
Male, Transcription, Genetic, Hypothalamus, Gene Expression Regulation, Developmental, Androgen Antagonists, Polymerase Chain Reaction, Embryonic and Fetal Development, Mice, Aromatase, 3-Oxo-5-alpha-Steroid 4-Dehydrogenase, Animals, Newborn, Linear Models, Animals, Female, RNA, Messenger, Cyproterone Acetate
Male, Transcription, Genetic, Hypothalamus, Gene Expression Regulation, Developmental, Androgen Antagonists, Polymerase Chain Reaction, Embryonic and Fetal Development, Mice, Aromatase, 3-Oxo-5-alpha-Steroid 4-Dehydrogenase, Animals, Newborn, Linear Models, Animals, Female, RNA, Messenger, Cyproterone Acetate
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