19-Nortestosterone influences neural stem cell proliferation and neurogenesis in the rat brain.
Abuse of androgenic anabolic steroids can affect brain function leading to behavioural changes. In this study, the effects of the testosterone analogue, 19-nortestosterone, on rat neural stem cells was examined. The androgen receptor is expressed by cultured embryonic and adult neural stem cells, and is also present in the ventricular epithelium during development and in the adult brain in, among others, dentate gyrus. In neural stem cells stimulated with epidermal growth factor, nandrolone reduced cell proliferation, especially in adult ones. The decrease was abolished by flutamide, a receptor antagonist. Nandrolone also decreased the BrdU labelling of neural stem cells in the dentate gyrus, demonstrating an effect of the hormone on cell proliferation in vivo. The effect of nandrolone was observed with both female and male rats but it was more pronounced in pregnant rats, indicating an involvement of oestrogen in nandrolone action. Nandrolone also decreased the number of newly born neuronal cells in the dentate gyrus of male rats. The results show that nandrolone has important effects on the proliferation and differentiation of neural stem cells expressing the cognate androgen receptor. The data show that the use of nandrolone may severely affect the formation of neural stem cells and could therefore have long-term negative consequences in the brain.
Brännvall
Karin
K
Department of Neuroscience, Unit of Neurobiology, Uppsala University, Biomedical Center, Husargatan 3, Box 587, S-75123 Uppsala, Sweden.
Bogdanovic
Nenad
N
Korhonen
Laura
L
Lindholm
Dan
D
D000367:Age Factors; D000726:Androgen Antagonists / Q000494:pharmacology; D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000166:cytology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004347:Drug Interactions; D004622:Embryo, Mammalian; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D005485:Flutamide / Q000494:pharmacology; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D009277:Nandrolone / Q000494:pharmacology*; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012737:Sex Factors; D013234:Stem Cells / Q000187:drug effects*
D000726:Androgen Antagonists; D000728:Androgens; D004967:Estrogens; D012333:RNA, Messenger; D011944:Receptors, Androgen; D004815:Epidermal Growth Factor; D009277:Nandrolone; D005485:Flutamide; D010751:Phosphopyruvate Hydratase; D001973:Bromodeoxyuridine