title: A new in vivo analysis model to detect sexually dimorphic rat liver cytochrome P450 gene expression dependent on growth hormone secretory patterns.
abstract: Several drug-metabolizing cytochrome P450 (CYP) enzymes exhibit sexual dimorphism depending on the pituitary growth hormone (GH) secretory patterns. However, the mechanism underlying CYP sexual dimorphism remains unclear. We previously established a transgenic (Alb-DsRed2 Tg) rat that expressed red fluorescent DsRed2 protein, particularly in hepatocytes, to visualize cell differentiation and multiplication and found that hepatic DsRed2 expression exhibited sexual dimorphism that was limited to adult males. In this study, we compared the expression patterns between sexual dimorphic Cyps and DsRed2 in Tg rats after experimentally reversing the GH secretory patterns in males and females. Postnatal day 1 male and female Tg rats were gonadectomized and then testosterone propionate (0.25 mg/rat) was subcutaneously administered to ovariectomized females immediately after surgery. Cyp mRNA and DsRed2 expression levels were quantified using RT-PCR and an in vivo imaging system, respectively. GH-dependent Cyps and hepatic DsRed2 expression patterns were reversed in males and females at 9 weeks after birth and were significantly correlated (P<0.05). This suggested that DsRed2 expression in these Tg rats depended on GH secretory patterns. Based on DsRed2 fluorescence, this Tg rat model could become a tool to readily and effectively evaluate changes in GH-dependent Cyp expression.
authors.affiliation: Divison of Laboratory Animal Science, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
authors.forename: Motoyo
authors.initials: M
authors.lastname: Maruyama
authors.forename: Masahiko
authors.initials: M
authors.lastname: Fujisawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Yokosuka
authors.forename: Toru R
authors.initials: TR
authors.lastname: Saito
authors.forename: Shin-Ichi
authors.initials: SI
authors.lastname: Hayama
authors.forename: Toshio
authors.initials: T
authors.lastname: Akimoto
authors.forename: Yoji
authors.initials: Y
authors.lastname: Hakamata
mesh_terms: D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D000072467:Cytochrome P450 Family 2 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D013006:Growth Hormone / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008164:Luminescent Proteins / Q000737:chemistry; D008297:Male; D023421:Models, Animal; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D055647:Rats, Transgenic; D017208:Rats, Wistar; D012727:Sex Characteristics; D039181:Steroid 16-alpha-Hydroxylase / Q000235:genetics* / Q000378:metabolism; D013250:Steroid Hydroxylases / Q000235:genetics* / Q000378:metabolism; D000097573:Red Fluorescent Protein
chemical_list: D001189:Aryl Hydrocarbon Hydroxylases; D000072467:Cytochrome P450 Family 2; D013006:Growth Hormone; D008164:Luminescent Proteins; D012333:RNA, Messenger; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases; D000097573:Red Fluorescent Protein; C450279:CYP2C11 protein, rat; C034694:steroid 15-beta-hydroxylase