Mouse conceptuses have a limited capacity to elevate the mRNA level of cellular retinoid binding proteins in response to teratogenic doses of retinoic acid.
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.
Harnish
D C
DC
Department of Biochemistry, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
Soprano
K J
KJ
Soprano
D R
DR
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*
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