Registration Number
0211U005219,
0107U012348
, R & D reports
Title
The studying of hormonal signal transduction including in mitotic and apoptotic processes in adrenal glands in physiological and pathological conditions
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Head
Tronko Mykola Dmytrovуch,
Registration Date
04-03-2011
Organization
State Institution "V.P. Komisarenko Institute of Endocrinology and Metabolism оf the Academy of Medical Scienses of Ukraine"
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Object of the study: Biochemical mechanisms of regulation of adrenocortical function, carcinogenesis and apoptosis in endocrine tissues. Aim of the study: To establish the role of signaling pathways of proliferative orientation and the role of programmed adrenal cell death in the development of abnormalities in their functional status, in particular, the role of modulators of both positive and negative effect in the regulation of steroidogenesis, metabolic processes in adrenocorticocytes and links of hypothalamic-pituitary axis. Results: The features of signaling networks of proliferative orientation in adrenocortical cells have been studied. It has been shown that the effect of such regulators of adrenocortical function as ACTH, estrogens and potassium ions is realized with involvement of a transcription factor AP-1. Estradiol induces a decreased expression of mRNA of a proapoptotic factor Bax and an impaired intensity of DNA fragmentation in human adrenocorticocytes. The antiapoptotic effect is accompanied by an increased expression of mRNA of a protein-regulator of rapid phase of steroidogenesis StAR and main enzyme of steroidogenesis Cytochrome P450scc. This may be due to the fact that estrogens activate not only those specific metabolic processes that lead to an intensification of steroidogenesis, but also adrenocorticocyte metabolism as a whole. A study of the effects of N-acylated ethanolamines in central links of hypothalamic-pituitary-adrenocortical axis has been continued. Administration of N-acylethanolamines led to a decrease in angiotensin-transforming enzyme activity in the hippocamp and adenohypophysis. The antimitotic drug Taxol enhanced apoptosis in the tissue of hormonally non-active adrenal tumours, but Taxol used as a single agent is not promising for the treatment of hormonally active tumours, because as a result of Taxol effect apoptotic processes in adrenocortical tissue remained unchanged. Under the effect of Taxol the synthesis of nucleic acids and protein in adrenocortical cells was decreasing, as well as cAMP level. Involvement of MDRI gene in adrenocortical cell resistivity to an adrenocoticolytic drug Chloditane has been established: use of PGP - an inhibitor of P-glycoprotein which is a product derived from MDRI gene - led to a significant increase in cytotoxic effect of adrenocoticolytic and antimitotic drugs on adrenocortical cells. Field of application: endocrinology, oncology
Product Description
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Гончар І.В.
Калинська Л.М.
Ковзун О.І.
Крохіна Т.І.
Левчук Н.І.
Лукашеня О.С.
Матасова С.Г.
Микоша О.С.
Пушкарьов В.М.
Тронько М.Д.
Цимбал Л.Т.
Шестакова В.В.
Яцко Н.В.
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2020-04-02
