title: Intrasplenic transplantation of isolated adult rat hepatocytes: sex-reversal and/or suppression of the major constituent isoforms of cytochrome P450.
abstract: Adult male and female rat hepatocytes were individually transplanted into the spleens of adult male and female rats. The recipients were euthanized at either eight, sixteen, thirty, or forty-five weeks following transplantation, at which time hepatic and splenic levels of liver-specific rat albumin mRNA as well as sex-dependent transcript levels of CYP2C11, -2C12, -2C7, -2A1, and -3A2-which accounts for > 60% of the total concentration of hepatic constituent cytochrome P450-were determined. Whereas the pre-infused hepatocytes expressed their expected cytochrome P450 sexual dimorphisms (female-specific CYP2C12, male-specific CYP3A2, and female-predominant CYP2A1), their post-transplantational competence now reflected the sexual dimorphisms of the recipient (as observed in the host's liver), which supports the concept that the sex-dependent growth hormone circulating profiles are the determinants regulating the expression levels of hepatic cytochrome P450. Also expressed at normal concentrations in the pre-infused hepatocytes, male-specific CYP2C11 and female-predominant CYP2C7 were inexplicably undetectable in the spleens of both recipient males and females, regardless of the sex of the donor hepatocytes, almost one year after transplantation.
authors.affiliation: Laboratories of Biochemistry, University of Pennsylvania, School of Veterinary Medicine, Philadelphia, Pennsylvania 19104-6048, USA.
authors.forename: Meena R
authors.initials: MR
authors.lastname: Sharma
authors.forename: Wojciech
authors.initials: W
authors.lastname: Dworakowski
authors.forename: Bernard H
authors.initials: BH
authors.lastname: Shapiro
mesh_terms: D000418:Albumins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D022781:Hepatocytes / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism / Q000637:transplantation*; D007527:Isoenzymes; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012727:Sex Characteristics; D013154:Spleen / Q000166:cytology / Q000201:enzymology / Q000378:metabolism / Q000601:surgery
chemical_list: D000418:Albumins; D007527:Isoenzymes; D012333:RNA, Messenger; D001189:Aryl Hydrocarbon Hydroxylases
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