Biomaterial Database

Regulation of multidrug resistance gene mdr1b/mdr1 expression in isolated mouse uterine epithelial cells. 1995

M T Kuo, and J Julian, and F Husain, and R Song, and D D Carson

Department of Molecular Pathology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.

The mammalian uterine epithelium (UE) undergoes drastic physiological and morphological changes during pregnancy. Steady-state levels of murine mdr1b mRNA, transcribed from a multidrug resistance gene encoding a membrane protein which functions as a transporter of lipophilic cytotoxic agents, are low in nonpregnant, cycling UE, but drastically increase (about 1,500- to 2,000-fold) at day 8 of gestation. At day 16 of gestation, levels of mdr1b mRNA are 2,500- to 3,000-fold higher than those in the cycling UE cells. Levels of mdr1b mRNA were elevated to levels comparable to those observed during pregnancy, in the UE of ovariectomized mice following 5-8 days of estrogen and progesterone administration. Withdrawal of these hormones resulted in a drastic reduction of mdr1b mRNA within 36 hr. These results suggested that steroid hormones alone can account for increased mdr1b mRNA expression and do not require the presence of other placenta/embryo-derived factors. Moreover, the hormonal effect on uterine mdr1b mRNA biosynthesis during pregnancy apparently is a delayed phenomenon. Nuclear run-on assays demonstrated that the rate of mdr1b transcription in UE cells prepared from 15-day pregnant mice (d-15 UE cells) was about two- to three-fold higher than that in nonpregnant UE cells. This increased transcription rate alone cannot account for mdr1b mRNA accumulation during pregnancy. mdr1b mRNA expression was investigated in primary cultures of d-15 UE cells. mdr1b mRNA levels decayed by 50% within 3-4 hr of culture and reached a steady-state 0.5-2% of initial levels by 24 hr. The rate of mdr1b mRNA decay in primary d-15 UE cells was decreased by treatment with alpha-amanitin or cycloheximide, suggesting that the decay pathway requires both transcription and de novo protein synthesis. Our results suggest that multiple mechanisms are involved in the maintenance of the high levels of mdr1b mRNA in pregnant UE cells. Furthermore, these data suggest that increased mRNA stability may contribute to the accumulation of mdr1b transcript during pregnancy.

UI	MeSH Term	Description	Entries
D008815	Mice, Inbred Strains	Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.	Inbred Mouse Strains,Inbred Strain of Mice,Inbred Strain of Mouse,Inbred Strains of Mice,Mouse, Inbred Strain,Inbred Mouse Strain,Mouse Inbred Strain,Mouse Inbred Strains,Mouse Strain, Inbred,Mouse Strains, Inbred,Strain, Inbred Mouse,Strains, Inbred Mouse
D011247	Pregnancy	The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.	Gestation,Pregnancies
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D003513	Cycloheximide	Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis.	Actidione,Cicloheximide
D004847	Epithelial Cells	Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.	Adenomatous Epithelial Cells,Columnar Glandular Epithelial Cells,Cuboidal Glandular Epithelial Cells,Glandular Epithelial Cells,Squamous Cells,Squamous Epithelial Cells,Transitional Epithelial Cells,Adenomatous Epithelial Cell,Cell, Adenomatous Epithelial,Cell, Epithelial,Cell, Glandular Epithelial,Cell, Squamous,Cell, Squamous Epithelial,Cell, Transitional Epithelial,Cells, Adenomatous Epithelial,Cells, Epithelial,Cells, Glandular Epithelial,Cells, Squamous,Cells, Squamous Epithelial,Cells, Transitional Epithelial,Epithelial Cell,Epithelial Cell, Adenomatous,Epithelial Cell, Glandular,Epithelial Cell, Squamous,Epithelial Cell, Transitional,Epithelial Cells, Adenomatous,Epithelial Cells, Glandular,Epithelial Cells, Squamous,Epithelial Cells, Transitional,Glandular Epithelial Cell,Squamous Cell,Squamous Epithelial Cell,Transitional Epithelial Cell
D004848	Epithelium	The layers of EPITHELIAL CELLS which cover the inner and outer surfaces of the cutaneous, mucus, and serous tissues and glands of the body.	Mesothelium,Epithelial Tissue,Mesothelial Tissue,Epithelial Tissues,Mesothelial Tissues,Tissue, Epithelial,Tissue, Mesothelial,Tissues, Epithelial,Tissues, Mesothelial
D005260	Female		Females
D005786	Gene Expression Regulation	Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.	Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D005796	Genes	A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.	Cistron,Gene,Genetic Materials,Cistrons,Genetic Material,Material, Genetic,Materials, Genetic
D000546	Amanitins	Cyclic peptides extracted from carpophores of various mushroom species. They are potent inhibitors of RNA polymerases in most eukaryotic species, blocking the production of mRNA and protein synthesis. These peptides are important in the study of transcription. Alpha-amanitin is the main toxin from the species Amanitia phalloides, poisonous if ingested by humans or animals.	Amanitin