title: Mouse conceptuses have a limited capacity to elevate the mRNA level of cellular retinoid binding proteins in response to teratogenic doses of retinoic acid.
abstract: In these studies, we wished to determine the effect of teratogenic doses of retinoic acid on the expression of cellular retinoic acid binding protein I (CRABP-I) mRNA, cellular retinoic acid binding protein II (CRABP-II) mRNA, cellular retinol binding protein I (CRBP-I) mRNA, and cellular retinol binding protein II (CRBP-II) mRNA in mouse conceptuses. Levels of CRABP-II mRNA and CRBP-I mRNA were modestly elevated (2.5-fold and 1.5-fold, respectively) in 9-day gestation conceptuses following treatment of dams with 100 mg/kg b.w. of retinoic acid. These levels were elevated by 6 hr following treatment and remained elevated until 48 and 24 hr, respectively. Two other retinoids, etretinate and retinoyl beta-glucuronide, also moderately elevated CRABP-II mRNA and CRBP-I mRNA levels in conceptuses. In contrast, the levels of CRABP-I mRNA in the conceptuses remained unaffected by treatment with any of these three retinoids. These results demonstrate that conceptuses have a limited capacity to elevate the cellular retinoid binding proteins mRNA levels and presumably the synthesis of their respective proteins in response to high, teratogenic doses of retinoic acid. As a result, an excess of free retinoic acid becomes available to the nuclear retinoic acid receptors, which may lead to inappropriate gene expression and eventual maldevelopment.
authors.affiliation: Department of Biochemistry, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
authors.forename: D C
authors.initials: DC
authors.lastname: Harnish
authors.forename: K J
authors.initials: KJ
authors.lastname: Soprano
authors.forename: D R
authors.initials: DR
authors.lastname: Soprano
mesh_terms: D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005050:Etretinate / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D005865:Gestational Age; D051379:Mice; D008815:Mice, Inbred Strains / Q000196:embryology*; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D012333:RNA, Messenger / Q000235:genetics; D018168:Receptors, Retinoic Acid; D012177:Retinol-Binding Proteins / Q000235:genetics*; D054840:Retinol-Binding Proteins, Cellular; D014212:Tretinoin / Q000031:analogs & derivatives / Q000494:pharmacology*
chemical_list: D002352:Carrier Proteins; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D012177:Retinol-Binding Proteins; D054840:Retinol-Binding Proteins, Cellular; C026787:retinoyl glucuronide; D014212:Tretinoin; D005050:Etretinate