Subject(s)
Ganglioneuroma/genetics , Neurofibromatosis 1/genetics , Spinal Neoplasms/genetics , Child, Preschool , DNA Mutational Analysis , Family , Female , Frameshift Mutation , Ganglioneuroma/pathology , Humans , Introns/genetics , Mutation , Neurofibromatosis 1/pathology , Neurofibromin 1/genetics , RNA Splicing , Spinal Neoplasms/pathologySubject(s)
Health Maintenance Organizations/legislation & jurisprudence , Tax Exemption/legislation & jurisprudence , Eligibility Determination/legislation & jurisprudence , Government Agencies , Group Practice, Prepaid/economics , Group Practice, Prepaid/legislation & jurisprudence , Health Maintenance Organizations/economics , Health Maintenance Organizations/organization & administration , Medicaid , Tax Exemption/standards , United States , UtahABSTRACT
We evaluated the effects of a methanol extract from the leaves of the plant Rosmarinus officinalis L. (rosemary) on the metabolism and action of estradiol and estrone. Treatment of female CD-1 mice with 2% rosemary in AIN-76A diet for 3 weeks increased the liver microsomal 2-hydroxylation of estradiol and estrone by approximately 150%, increased their 6-hydroxylation by approximately 30% and inhibited the 16alpha-hydroxylation of estradiol by approximately 50%. Treatment of female CD-1 mice with 2% rosemary diet for 3 weeks also stimulated the liver microsomal glucuronidation of estradiol and estrone by 54-67% and 37-56%, respectively. In additional studies, feeding 2% rosemary diet to ovariectomized CD-1 mice for 3 weeks inhibited the uterotropic action of estradiol and estrone by 35-50% compared with animals fed a control diet. The results of this study showed that feeding female mice a 2% rosemary diet increased the liver microsomal oxidation and glucuronidation of estradiol and estrone and inhibited their uterotropic action.
Subject(s)
Estrogens/metabolism , Lamiaceae/chemistry , Microsomes, Liver/drug effects , Plant Extracts/pharmacology , Uterus/physiology , Animals , Diet , Estrogens/physiology , Female , Glucuronates/metabolism , Hydroxylation , Mice , Microsomes, Liver/metabolism , NADP/metabolism , Plant Extracts/administration & dosage , Steroid 16-alpha-HydroxylaseABSTRACT
Administration of 0.5 or 1% lyophilized green tea (5 or 10 mg tea solids per ml, respectively) as the sole source of drinking fluid to female Long-Evans rats for 18 days stimulated liver microsomal glucuronidation of estrone, estradiol and 4-nitrophenol by 30-37%, 15-27% and 26-60%, respectively. Oral administration of 0.5% lyophilized green tea to female CD-1 mice for 18 days stimulated liver microsomal glucuronidation of estrone, estradiol and 4-nitrophenol by 33-37%, 12-22% and 172-191%, respectively. The in vitro addition of a green tea polyphenol mixture, a black tea polyphenol mixture or (-)-epigallocatechin gallate inhibited rat liver microsomal glucuronidation of estrone and estradiol in a concentration-dependent manner and their IC50 values for inhibition of estrogen metabolism were approximately 12.5, 50 and 10 microg/ml, respectively. Enzyme kinetic analysis indicates that the inhibition of estrone glucuronidation by 10 microM (-)-epigallocatechin gallate was competitive while inhibition by 50 microM (-)-epigallocatechin gallate was noncompetitive. Similarly, several flavonoids (naringenin, hesperetin, kaempferol, quercetin, rutin, flavone, alpha-naphthoflavone and beta-naphthoflavone) also inhibited rat liver microsomal glucuronidation of estrone and estradiol to varying degrees. Naringenin and hesperetin displayed the strongest inhibitory effects (IC50 value of approximately 25 microM). These two hydroxylated flavonoids had a competitive mechanism of enzyme inhibition for estrone glucuronidation at a 10 microM inhibitor concentration and a predominantly noncompetitive mechanism of inhibition at a 50 microM inhibitor concentration.
Subject(s)
Estradiol/metabolism , Flavanones , Flavonoids/pharmacology , Hesperidin , Microsomes, Liver/drug effects , Phenols/pharmacology , Polymers/pharmacology , Tea/chemistry , Animals , Enzyme Inhibitors/pharmacology , Estrone/metabolism , Female , Glucuronates/metabolism , Glucuronosyltransferase/metabolism , Kinetics , Mice , Mice, Inbred Strains , Microsomes, Liver/enzymology , Nitrophenols/metabolism , Rats , Rats, Inbred Strains , Uridine Diphosphate Glucuronic Acid/metabolismABSTRACT
A sialoglycopeptide (SGP), isolated and purified from bovine cerebral cortex cells, was studied in regard to early signal transduction events associated with the cell cycle. Previously shown to be a potent antagonist to a variety of mitogens, the SGP abrogated the ability of 12-O-tetradecanoylphorbol-13 acetate (TPA) to elicit an alkalinization of 3T3 cell cytosol, but only when added minutes prior to, or simultaneously with, the tumor promoter. 3T3 cell TPA-mediated Ca2+ mobilization was also inhibited by the SGP although the inhibitor itself did not bind Ca2+ in a cell-free assay. The results are discussed in light of the already known kinetics of interaction between the SGP, various mitogens, and the calcium ionophore A23187 with regard to the pivotal events leading to the decision of a cell to divide or not to divide.