Opposite effects of glucocorticoid on hepatic 11 beta-hydroxysteroid dehydrogenase mRNA and activity in fetal and adult sheep. 1994

K Yang, and E T Berdusco, and J R Challis
Department of Obstetrics and Gynecology, Lawson Research Institute, University of Western Ontario, St Joseph's Health Centre, London, Canada.

The level of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) mRNA in the fetal sheep liver increases dramatically between day 130 and term (term = day 145), but the causal factors remain unknown. The present study was designed to determine the effects of exogenous glucocorticoid on the fetal hepatic 11 beta-HSD gene expression. Dexamethasone (dex; 2 micrograms/min over 15 min every 2 h) or saline was infused into chronically-catheterized fetal sheep at day 130 of gestation for 4 days. At the end of infusion, the lower right lobe of the liver was collected, total cellular RNA extracted and subjected to Northern blot analysis. It was found that the level of the hepatic 11 beta-HSD mRNA in dex-treated fetuses was about four times higher than that in the saline-treated controls. To examine whether changes occur in the response of hepatic 11 beta-HSD gene expression to glucocorticoids in adulthood, we also treated non-pregnant ewes with dex (10 mg/day) for 4 days. By contrast, this treatment regime in adult sheep produced a small but significant decrease in hepatic 11 beta-HSD mRNA levels. We also determined whether age-specific changes in the hepatic level of 11 beta-HSD mRNA following dex treatment were reflected in the level of 11 beta-HSD enzyme activity. Hepatic 11 beta-HSD activity was determined by a standard in vitro conversion assay using cortisol and cortisone as physiological substrates. In both fetal and adult livers, 11-oxoreductase activity (cortisone-->cortisol) was predominant.(ABSTRACT TRUNCATED AT 250 WORDS)

UI MeSH Term Description Entries
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D003348 Cortisone A naturally occurring glucocorticoid that has been used in replacement therapy for ADRENAL INSUFFICIENCY and as an anti-inflammatory agent. Cortisone itself is inactive; it is converted in the liver to the active metabolite HYDROCORTISONE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p726) 17-Hydroxy-3,11,20-trioxopregn-4-en-21-yl acetate,Adreson,Cortisone Acetate,Cortone Acetate
D003907 Dexamethasone An anti-inflammatory 9-fluoro-glucocorticoid. Hexadecadrol,Decaject,Decaject-L.A.,Decameth,Decaspray,Dexasone,Dexpak,Hexadrol,Maxidex,Methylfluorprednisolone,Millicorten,Oradexon,Decaject L.A.
D004789 Enzyme Activation Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D005260 Female Females
D006854 Hydrocortisone The main glucocorticoid secreted by the ADRENAL CORTEX. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions. Cortef,Cortisol,Pregn-4-ene-3,20-dione, 11,17,21-trihydroxy-, (11beta)-,11-Epicortisol,Cortifair,Cortril,Epicortisol,Hydrocortisone, (11 alpha)-Isomer,Hydrocortisone, (9 beta,10 alpha,11 alpha)-Isomer,11 Epicortisol
D006913 Hydroxysteroid Dehydrogenases Enzymes of the oxidoreductase class that catalyze the dehydrogenation of hydroxysteroids. (From Enzyme Nomenclature, 1992) EC 1.1.-. Hydroxysteroid Dehydrogenase,Dehydrogenase, Hydroxysteroid,Dehydrogenases, Hydroxysteroid
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D012756 Sheep Any of the ruminant mammals with curved horns in the genus Ovis, family Bovidae. They possess lachrymal grooves and interdigital glands, which are absent in GOATS. Ovis,Sheep, Dall,Dall Sheep,Ovis dalli

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