Biomaterial Database

Changes in progesterone binding and metabolism in liver microsomes from persistent hepatocyte nodules and hepatomas in male rats. 1986

G Feuer, and L Stuhne-Sekalec, and M W Roomi, and R G Cameron

Hepatocyte nodules that persist throughout chemical carcinogenesis are linked to carcinomas both as one site at which hepatomas are seen to arise and as a tissue which shows more than a dozen significant protein changes also found in liver cancers. In view of the differential stimulus to growth of these persistent nodules by progesterone, progesterone metabolism and binding to the microsomes of nodules and hepatomas were studied. Progesterone metabolizing enzyme activities in nodule microsomes showed striking shifts with a 42% decrease in 16 alpha-hydroxylase activity and a 2- to 3-fold increase in 6 beta-hydroxylase activity compared to control levels. Hepatomas had a dramatic 20-fold increase relative to nodules or controls in the reductive pathway for progesterone metabolism as measured by delta 4-5 alpha-hydrogenase activity. The rate and saturation of the specific binding of progesterone to microsomes of nodules and liver cancers were significantly decreased when compared either to the tissue surrounding the nodules or to their respective control microsomes. This change in progesterone binding of nodular microsomes may relate to an altered balance of progesterone content and its metabolites in the nodular cells or to alterations in the microsomal membrane binding site. The functional significance of reduced binding of progesterone for liver carcinogenesis is thus open to further inquiry.

UI	MeSH Term	Description	Entries
D007425	Intracellular Membranes	Thin structures that encapsulate subcellular structures or ORGANELLES in EUKARYOTIC CELLS. They include a variety of membranes associated with the CELL NUCLEUS; the MITOCHONDRIA; the GOLGI APPARATUS; the ENDOPLASMIC RETICULUM; LYSOSOMES; PLASTIDS; and VACUOLES.	Membranes, Intracellular,Intracellular Membrane,Membrane, Intracellular
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
D008114	Liver Neoplasms, Experimental	Experimentally induced tumors of the LIVER.	Hepatoma, Experimental,Hepatoma, Morris,Hepatoma, Novikoff,Experimental Hepatoma,Experimental Hepatomas,Experimental Liver Neoplasms,Hepatomas, Experimental,Neoplasms, Experimental Liver,Experimental Liver Neoplasm,Liver Neoplasm, Experimental,Morris Hepatoma,Novikoff Hepatoma
D008297	Male		Males
D008862	Microsomes, Liver	Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.	Liver Microsomes,Liver Microsome,Microsome, Liver
D011374	Progesterone	The major progestational steroid that is secreted primarily by the CORPUS LUTEUM and the PLACENTA. Progesterone acts on the UTERUS, the MAMMARY GLANDS and the BRAIN. It is required in EMBRYO IMPLANTATION; PREGNANCY maintenance, and the development of mammary tissue for MILK production. Progesterone, converted from PREGNENOLONE, also serves as an intermediate in the biosynthesis of GONADAL STEROID HORMONES and adrenal CORTICOSTEROIDS.	Pregnenedione,Progesterone, (13 alpha,17 alpha)-(+-)-Isomer,Progesterone, (17 alpha)-Isomer,Progesterone, (9 beta,10 alpha)-Isomer
D003577	Cytochrome P-450 Enzyme System	A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.	Cytochrome P-450,Cytochrome P-450 Enzyme,Cytochrome P-450-Dependent Monooxygenase,P-450 Enzyme,P450 Enzyme,CYP450 Family,CYP450 Superfamily,Cytochrome P-450 Enzymes,Cytochrome P-450 Families,Cytochrome P-450 Monooxygenase,Cytochrome P-450 Oxygenase,Cytochrome P-450 Superfamily,Cytochrome P450,Cytochrome P450 Superfamily,Cytochrome p450 Families,P-450 Enzymes,P450 Enzymes,Cytochrome P 450,Cytochrome P 450 Dependent Monooxygenase,Cytochrome P 450 Enzyme,Cytochrome P 450 Enzyme System,Cytochrome P 450 Enzymes,Cytochrome P 450 Families,Cytochrome P 450 Monooxygenase,Cytochrome P 450 Oxygenase,Cytochrome P 450 Superfamily,Enzyme, Cytochrome P-450,Enzyme, P-450,Enzyme, P450,Enzymes, Cytochrome P-450,Enzymes, P-450,Enzymes, P450,Monooxygenase, Cytochrome P-450,Monooxygenase, Cytochrome P-450-Dependent,P 450 Enzyme,P 450 Enzymes,P-450 Enzyme, Cytochrome,P-450 Enzymes, Cytochrome,Superfamily, CYP450,Superfamily, Cytochrome P-450,Superfamily, Cytochrome P450
D004052	Diethylnitrosamine	A nitrosamine derivative with alkylating, carcinogenic, and mutagenic properties.	Nitrosodiethylamine,N-Nitrosodiethylamine,N Nitrosodiethylamine
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
D013250	Steroid Hydroxylases	Cytochrome P-450 monooxygenases (MIXED FUNCTION OXYGENASES) that are important in steroid biosynthesis and metabolism.	Steroid Hydroxylase,Steroid Monooxygenases,Hydroxylase, Steroid,Hydroxylases, Steroid,Monooxygenases, Steroid