Structural specificity of steroids in stimulating DNA synthesis and protooncogene expression in primary rat hepatocyte cultures
| Autor: | Anthony M. Edwards, Chow H. Lee |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
DNA Replication
Male medicine.medical_specialty Anabolism Endocrinology Diabetes and Metabolism medicine.medical_treatment Clinical Biochemistry Stimulation Biology Biochemistry Structure-Activity Relationship Endocrinology Internal medicine Proto-Oncogenes medicine Structure–activity relationship Animals Rats Wistar Molecular Biology Cells Cultured DNA synthesis Cell Biology Rats Steroid hormone medicine.anatomical_structure Gene Expression Regulation Hepatocyte Pregnenolone Hepatocytes Molecular Medicine Steroids Anabolic steroid medicine.drug |
| Zdroj: | The Journal of steroid biochemistry and molecular biology. 81(1) |
| ISSN: | 0960-0760 |
| Popis: | Among the chemical compounds of varied structure which possess liver tumour-promoting are steroids, such as estrogens, pregnenolone derivatives and anabolic steroids. Although the mechanism(s) of tumour promotion in liver by these xenobiotics is not well understood, it is clear that growth stimulation is one important element in their action. As a basis for better defining whether steroids stimulate growth by a common mechanism or fall into sub-groups with differing actions, the effects of 46 steroids on DNA synthesis and the expression of protooncogenes c-fos and c-myc were examined in primary cultures of normal rat hepatocytes. Tentative groupings of steroids have been identified based on apparent structural requirements for stimulation of DNA synthesis, and effects of auxiliary factors in modulating this growth stimulus. For a "progestin" group, insulin appeared to be permissive for stimulation of DNA synthesis, and presence of an ester or hydroxyl group at 17alpha-position in combination with a non-polar group at C(6) appeared to be required for stimulation. For the pregnenes, dexamethasone was stimulatory. Structural requirements include a non-polar substitution at 16alpha-position and presence of a 6alpha-methyl group. Androgens were weak or ineffective stimulators of DNA synthesis. Anabolic steroids were weak to strong stimulators and alteration to A ring structure in combination with non-polar substitution at 17alpha-position appeared to be required for the activity. With the exception of the anabolic steroid, dianabol, there do not appear to be strong correlation between ability to stimulate DNA synthesis and ability to induce protooncogene expression among the steroids. This study provides a starting point for future more detailed examination of growth-stimulatory mechanism(s) of action of steroids in the liver. |
| Databáze: | OpenAIRE |
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