Expression of the estrogen-inducible EGFP gene in aromatase-null mice reveals differential tissue responses to estrogenic compounds.
Aromatase is an enzyme responsible for the conversion of androgen to estrogen. We genetically engineered an aromatase-deficient mouse (Ar(-/-) mouse) to express an enhanced green fluorescent protein (EGFP) gene in the uterus, ovary, adrenal and pituitary glands in a 17beta-estradiol (E2)-inducible manner. In this study, we analyzed estrogenic activities of diethylstilbestrol, genistein, daidzein and E2 in the Ar(-/-) tissues by using the EGFP expression as an indicator. These analyses manifest differential responses of the tissues to the compounds and also allow to determine the relative estrogenic potency of the compounds to that of E2 in vivo. Furthermore, analyses of the EGFP expression in ERalpha-deficient mice suggested that the expression is ERalpha-dependent in the uterus and pituitary gland. In conclusion, the Ar(-/-) mouse carrying the E2-inducible EGFP gene is a valuable tool for quantitative analyses of natural and synthetic estrogenic compounds in vivo.
Toda
Katsumi
K
Department of Molecular Genetics, School of Medicine, Kochi University, Oko-cho, Nankoku, Kochi 783-8505, Japan. todak@med.kochi-u.ac.jp
Hayashi
Yoshihiro
Y
Okada
Teruhiko
T
Morohashi
Ken-ichirou
K
Saibara
Toshiji
T
D000311:Adrenal Glands / Q000187:drug effects / Q000201:enzymology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001141:Aromatase / Q000235:genetics / Q000502:physiology*; D004054:Diethylstilbestrol / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000502:physiology; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology; D005260:Female; D019833:Genistein / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism*; D006720:Homozygote; D007529:Isoflavones / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D010053:Ovary / Q000187:drug effects / Q000201:enzymology; D048789:Phytoestrogens / Q000494:pharmacology; D010902:Pituitary Gland / Q000187:drug effects / Q000201:enzymology; D014599:Uterus / Q000187:drug effects / Q000201:enzymology
D000970:Antineoplastic Agents; D047628:Estrogen Receptor alpha; D004968:Estrogens, Non-Steroidal; D007529:Isoflavones; D048789:Phytoestrogens; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D004958:Estradiol; C004742:daidzein; D004054:Diethylstilbestrol; D019833:Genistein; D001141:Aromatase