ABSTRACT
The effect of different concentrations of N-stearoylethanolamine (NSE 18:0) on fragmentation of DNA in the tumoural and extratumour tissues of the adrenal glands in vitro was studied. In this work the following types of tissue were investigated: extratumoural tissue from patients with hormonally active tumours, benign tumour tissue (hormonally active and hormonally inactive), tissue of malignant tumours and hyperplasic tissue of the adrenal glands (Itsenko-Cushing disease). It has been established that the NSE increases the intensity of DNA fragmentation only in the tissue of hormonally inactive tumours. Benign hormonally active tumours, malignant tumours and hyperplastic tissue of the adrenal glands were resistant to the NSE. The possible mechanisms of resistance to the drug are discussed.
Subject(s)
Adrenal Glands/drug effects , Antineoplastic Agents/pharmacology , Antioxidants/pharmacology , DNA Fragmentation/drug effects , Ethanolamines/pharmacology , Stearic Acids/pharmacology , Adrenal Cortex Hormones/metabolism , Adrenal Gland Neoplasms/drug therapy , Adrenal Gland Neoplasms/metabolism , Adrenal Gland Neoplasms/pathology , Adrenal Glands/metabolism , Adrenal Glands/pathology , Cushing Syndrome/drug therapy , Cushing Syndrome/metabolism , Cushing Syndrome/pathology , Drug Resistance, Neoplasm , Humans , Hyperplasia/drug therapy , Hyperplasia/metabolism , Hyperplasia/pathology , Microtomy , Neoplasms/drug therapy , Neoplasms/metabolism , Neoplasms/pathology , Organ Specificity , Tissue Culture Techniques , Tumor MicroenvironmentABSTRACT
The effect of different potassium concentrations on changes in steroidogenic acute regulatory protein (StAR) and cytochrome P-450(SCC) in human adrenal cortex tissue was studied. A rise in K+ concentration in incubation medium to 8.5 mM caused an increase in StAR and cytochrome P-450(SCC) mRNA level in adrenocorticocytes by 70 and 76%, respectively, compared with control. Thus, potassium ions caused an enhancement of minerocorticoid synthesis in the adrenal cortex, which is associated with mechanisms that regulate the intensity of expression of StAR and cytochrome P-450(SCC) on a transcriptional level.
Subject(s)
Adrenal Cortex/drug effects , Cholesterol Side-Chain Cleavage Enzyme/genetics , Phosphoproteins/genetics , Potassium/pharmacology , Adrenal Cortex/metabolism , Cholesterol/metabolism , Cholesterol Side-Chain Cleavage Enzyme/metabolism , Electrophoresis, Agar Gel , Gene Expression , Humans , Phosphoproteins/metabolism , Polymerase Chain Reaction , Potassium/metabolism , RNA, Messenger/analysis , RNA, Messenger/biosynthesis , Tissue Culture TechniquesABSTRACT
A comparative analysis of the expression of both, RET/PTC1 and RET/PTC3 oncogenes in papillary thyroid carcinomas (PTC) of patients from different age groups was carried out. Those were the following groups: children (mean age - 13 years, mean latency period - 13 years), young adults (mean age - 24 years, mean latency period - 14 years), adults (mean age - 38 years, mean latency period - 22 years). The presence of RET/PTC oncogenes was detected using polymerase chain reaction. In all cases the samples of both tumor and normal thyroid tissue were studied. It was established that induction of both, RET/PTC1 and RET/PTC3 rearrangements was present only in carcinoma samples. In PTCs the percentage of RET/PTC-positive tumors with increasing the age of patients has been decreasing. It should be noted that the part of carcinomas with induction of RET/PTC1 did not change with increasing the age of patients. At the same time the frequency of RET/PTC3 rearrangements with the increasing both the latency period and age of patients, significantly decreased. In conclusion, our data can evidence for the presence of correlation between the age of patients, latency period and induction of RET/PTC3 oncogenes.
Subject(s)
Neoplasms/genetics , Protein Isoforms/genetics , Proto-Oncogene Proteins c-ret/genetics , Adolescent , Adult , Age Factors , Carcinoma , Carcinoma, Papillary , Causality , Chernobyl Nuclear Accident , Female , Gene Expression Regulation, Neoplastic , Humans , Male , Neoplasms/epidemiology , Neoplasms/metabolism , Neoplasms/pathology , Polymerase Chain Reaction , Protein Isoforms/metabolism , Proto-Oncogene Proteins c-ret/metabolism , Thyroid Cancer, Papillary , Thyroid Neoplasms/epidemiology , Thyroid Neoplasms/genetics , Thyroid Neoplasms/metabolism , Thyroid Neoplasms/pathology , Tumor Microenvironment , Ukraine , Young AdultABSTRACT
The data on the role of protein kinase C enzymes family in regulation of biochemical processes in adrenocortical cells and other types of steroid-producing cells were analyzed. The involvement of these protein kinase reactions in signal transduction of main regulators of adrenocortical function--ACTH, angiotensin II and potassium ions was considered. Data about interactions and transregulation influences between different secondary messenger systems, which mediate intracellular signal transduction of agonists and provide functional activity of adrenocortical cells are discussed. The participation of protein kinase C is shown in changing of the steroidogenic genes expression. The role of protein kinase C isoforms in tumorogenesis is described.
Subject(s)
Adrenal Cortex , Protein Kinase C , Adrenal Cortex/cytology , Adrenal Cortex/enzymology , Adrenal Cortex/metabolism , Adrenocorticotropic Hormone/metabolism , Angiotensin II/metabolism , Animals , Humans , Potassium/metabolism , Protein Kinase C/classification , Protein Kinase C/metabolism , Protein Kinase C/physiologyABSTRACT
The messenger mechanisms mediating K+ regulatory signals in human adrenocorticocytes were studied. It was shown that potassium ions initiated decay of polyphosphoinositides to inositolphosphates and obviously diacylglycerol. The latter compounds activate protein kinase C as affected by different agonists. Using western blotting method we showed translocation of PKCalpha from cytosol to membranes after adrenal tissue preincubation in the medium with increased K+ content (8.5 mM). Translocation means activation of the enzyme. Activity of PKC increased in the microsomal fraction and did not change in cytosol. Increased concentration of K+ in the incubation medium also activates protein kinase A, although to a lesser extent compared to PKC. Unlike PKC activity of PKA was changed in cytosol as well. The possibility of involvement of several messenger systems in K+ signal transduction in human adrenocortical cells as well as the hypothesis on cross-talk between messenger mechanisms for main physiological agonists controlling aldosterone biosynthesis in the adrenals are discussed.
