Cytochrome P450 aromatase (CYP19) in the non-human primate brain: distribution, regulation, and functional significance.
In adult male primates, estrogens play a role in both gonadotropin feedback and sexual behavior. Inhibition of aromatization in intact male monkeys acutely elevates serum levels of luteinizing hormone, an effect mediated, at least partially, within the brain. High levels of aromatase (CYP19) are present in the monkey brain and regulated by androgens in regions thought to be involved in the central regulation of reproduction. Androgens regulate aromatase pretranslationally and androgen receptor activation is correlated with the induction of aromatase activity. Aromatase and androgen receptor mRNAs display both unique and overlapping distributions within the hypothalamus and limbic system suggesting that androgens and androgen-derived estrogens regulate complimentary and interacting genes within many neural networks. Long-term castrated monkeys, like men, exhibit an estrogen-dependent neural deficit that could be an underlying cause of the insensitivity to testosterone that develops in states of chronic androgen deficiency. Future studies of in situ estrogen formation in brain in the primate model are important for understanding the importance of aromatase not only for reproduction, but also for neural functions such as memory and cognition that appear to be modulated by estrogens.
Roselli
C E
CE
Department of Physiology and Pharmacology, Oregon Health and Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97201-3098, USA. rosellic@ohsu.edu
Resko
J A
JA
D000728:Androgens / Q000378:metabolism; D000818:Animals; D001141:Aromatase / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000201:enzymology* / Q000502:physiology; D004351:Drug Resistance; D004967:Estrogens / Q000378:metabolism; D005246:Feedback; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007986:Luteinizing Hormone / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D012726:Sexual Behavior, Animal / Q000502:physiology; D013739:Testosterone / Q000378:metabolism / Q000494:pharmacology; D014018:Tissue Distribution
D000728:Androgens; D004967:Estrogens; D012333:RNA, Messenger; D011944:Receptors, Androgen; D013739:Testosterone; D007986:Luteinizing Hormone; D001141:Aromatase