The aromatase inhibitor fadrozole and the 5-reductase inhibitor finasteride affect gonadal differentiation and gene expression in the frog Silurana tropicalis.
Aromatase (cyp19) and the 5alpha- and 5beta-reductases (srd5alpha and srd5beta) are important enzymes for vertebrate sexual development. We investigated the effects of inhibition of cyp19 by fadrozole (FAD), and srd5alpha and srd5beta by finasteride (FIN) during anuran larval development. Chronic exposures of Silurana (Xenopus) tropicalis from Nieuwkoop-Faber stage 12 until stage 60 were performed using either 2 microM FAD or 25 microM FIN. Histological analysis of exposed metamorphic frogs revealed that both treatments induced intersex individuals (presence of testicular oocytes). FAD treatment resulted in 55% male, 30% female and 15% intersex, while FIN treatment produced 27% male, 53% female and 20% intersex. Real-time RT-PCR analysis of hepatic sex steroid- and thyroid hormone-related gene expression demonstrated that FAD-induced intersex animals had higher srd5alpha1, srd5alpha2 and eralpha mRNA levels than control and FAD males. In contrast, FIN-induced intersex had low srd5alpha1, srd5alpha2, srd5beta and dio3 and high dio2 mRNA levels. FIN-treated males exhibited high trbeta, dio2 and a lower dio3 mRNA levels. We conclude that chemically induced intersex animals display different gene expression profiles than non-exposed animals and that, although morphologically similar, intersex animals produced by different chemicals have different endocrine pathophysiologies.
Centre for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa, Ottawa, Ont., Canada.
P
P
Duarte-Guterman
V S
VS
Langlois
K
K
Hodgkinson
B D
BD
Pauli
G M
GM
Cooke
M G
MG
Wade
V L
VL
Trudeau
D000818:Animals; D001141:Aromatase; D047072:Aromatase Inhibitors / Q000494:pharmacology; D017316:Fadrozole / Q000494:pharmacology*; D005260:Female; D018120:Finasteride / Q000494:pharmacology*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D012739:Gonadal Steroid Hormones / Q000235:genetics / Q000378:metabolism; D006066:Gonads / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008297:Male; D008675:Metamorphosis, Biological / Q000187:drug effects / Q000235:genetics; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012733:Sex Differentiation / Q000187:drug effects / Q000235:genetics*; D012744:Sex Ratio; D013963:Thyroid Hormones / Q000235:genetics / Q000378:metabolism; D014981:Xenopus / Q000235:genetics* / Q000254:growth & development
D047072:Aromatase Inhibitors; D012739:Gonadal Steroid Hormones; D012333:RNA, Messenger; D013963:Thyroid Hormones; D018120:Finasteride; D001141:Aromatase; D044925:Oxidoreductases Acting on CH-CH Group Donors; D017316:Fadrozole