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Сродство дидрогестерона и других прогестинов к эстрогеновым, прогестероновым и другим типам стероидных рецепторов
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Аннотация
Обзор. Расчет энергий связывания позволяет оценить сродство различных естественных и синтетических прогестинов к разным типам стероидных рецепторов. Количественные характеристики сродства различных прогестинов к разным типам рецепторов – современная основа для подбора индивидуализированной заместительной гормональной терапии. Молекула дидрогестерона обладает максимальным сродством к рецептору прогестерона, а к другим стероидным рецепторам (эстрогенным, андрогенным, минерало- и глюкокортикоидным) – минимальным. Сравнительное биоинформационное исследование прогестинов, входящих в состав препаратов Анжелик, Ливиал, Премпро, Климонорм и Фемостон позволяет оценить баланс «эффективность-безопасность».
Ключевые слова: прогестины, заместительная гормональная терапия, дидрогестерон, энергия связывания, биоинформатика, Фемостон, Анжелик, Ливиал, Премпро, Климонорм (левоноргестрел).
Ключевые слова: прогестины, заместительная гормональная терапия, дидрогестерон, энергия связывания, биоинформатика, Фемостон, Анжелик, Ливиал, Премпро, Климонорм (левоноргестрел).
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A review. Estimations of binding energy allowed to evaluate the affinity of various natural and synthetic progestins to different steroid receptors. Current approach to individual tailoring of replacement hormone therapy is based on quantitative affinity characteristics of various progestins to different types of receptors. The dydrogesterone molecule has the maximal affinity to a progesterone-receptor and minimal – to other (estrogenic, androgenic, mineralocorticoid, and glucocorticoid) steroid receptors. Comparative bioinformatic study of progestins as active ingredients of Angeliq, Livial, Prempro, Klimonorm, and Femoston preparations allows to evaluate «efficiency-safety» balance for this compounds.
Key words: progestins, replacement hormone therapy, dydrogesterone, binding energy, bioinformatics, Femoston, Angeliq, Livial, Prempro, Klimonorm (levonorgestrel).
Полный текст
Список литературы
1. Rossouw J, Anderson G, Prentice R et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA 2002; 288 (3): 321–33.
2. Chlebowski R, Kuller L, Prentice R et al. Breast cancer after use of estrogen plus progestinin postmenopausal women. N Engl J Med 2009; 360 (6): 573–87.
3. George J, Colman R, Goldhaber S, Victor J. Marder (2006). Hemostasis and thrombosis: basic principles and clinical practice. Hagerstwon, MD: Lippincott Williams & Wilkins: 1239. ISBN 0781749964.
4. Anderson G, Limacher M, Assaf A, et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA 2004; 291 (14): 1701–12.
5. Manson J, Hsia J, Johnson K, Rossouw J et al. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med 2003; 349 (6): 523–34.
6. Torshin I Yu. Bioinformatics in the post-genomic era: physiology and medicine. Nova Biomedical, ISBN 9781600 217524. 2007.
7. Сухих Г.Т., Торшин И.Ю., Громова О.А. Молекулярные механизмы дидрогестерона (дюфастона). Ч. 1: исследование селективности взаимодействия дидрогестерона с прогестероновыми рецепторами методами молекулярной механики. Гинекология. 2009; 12: 62–7.
8. Торшин И.Ю., Громова О.А., Сухих Г.Т. Молекулярные механизмы дидрогестерона (дюфастона). Ч. 2: полногеномное исследование транскрипционных эффектов рецепторов прогестерона, андрогенов и эстрогенов. Гинекология. 2010; 1: 6–12.
9. Торшин И.Ю., Громова О.А. 25 мгновений молекулярной фармакологии: о развитии клинико-фармакологического мышления. А-Гриф, 2011.
10. Torshin I.Yu.. Bioinformatics in the Post-Genomic Era: The Role of Biophysics, 2006 Nova Biomedical Books, NY, ISBN: 1-60021-048.
11. Torshin IY. Computed energetics of nucleotides in spatial ribozyme structures: an accurate identification of functional regions from structure. ScientificWorldJournal 2004; 26 (4): 228–47.
12. Gadkar-Sable S, Shah C, Rosario G et al. Progesterone receptors: various forms and functions in reproductive tissues. Front Biosci 2005; 10: 2118–30.
13. Schindler A, Campagnoli C, Druckmann R et al. Classification and pharmacology of progestins. Maturitas 2003; 46 (l): 7–16.
14. van Amsterdam PH, Overmars H, Scherpenisse PM et al. Dydrogesterone: Metabolism in man. Eur J Drug Metab Pharmacokinet 1980; 5: 173–84.
15. Schindler A, Campagnoli C, Druckmann R et al.Classification and pharmacology of progestins. Maturitas 2008; 61 (1–2): 171–80.
16. Escande A, Servant N, Rabenoelina F et al. Regulation of activities of steroid hormone receptors by tibolone and its primary metabolites. J Steroid Biochem Mol Biol 2009; 116 (1–2): 8–14.
17. Al Kadri H, Hassan S, Al-Fozan H, Hajeer A. Hormone therapy for endometriosis and surgical menopause. Cochrane Database Syst Rev 2009; 1: CD005997.
18. Garefalakis M, Hickey M. Role of androgens, progestins and tibolone in the treatment of menopausal symptoms: a review of the clinical evidence. Clin Interv Aging 2008; 3 (1): 1–8.
19. Lazovic G, Radivojevic U, Marinkovic J. Tibolone: the way to beat many a postmenopausal ailments. Expert Opin Pharmacother 2008; 9 (6): 1039–47.
20. Dӧren M, Rübig A, Coelingh Bennink H, Holzgreve W. Differential effects on the androgen status of postmenopausal women treated with tibolone and continuous combined estradiol and norethindrone acetate replacement therapy. Fertil Steril 2001; 75 (3): 554–9.
21. Raobaikady B, Parsons M, Reed M, Purohit A. Tibolone and its delta-4, 7alpha-methyl norethisterone metabolite are reversible inhibitors of human aromatase. J Steroid Biochem Mol Biol 2007; 104 (3–5): 154–60.
22. Krattenmacher R. Drospirenone: pharmacology and pharmacokinetics of a unique progestogen. Contraception 2000; 62 (1): 29–38.
23. Pullen M, Laping N, Edwards R, Bray J. Determination of conformational changes in the progesterone receptor using ELISA-like assays. Steroids 2006; 71 (9): 792–8.
24. Edgren R, Stanczyk F. Nomenclature of the gonane progestins. Contraception 60 (6): 313.
25. Sitruk-Ware R. New progestagens for contraceptive use. Hum Reprod Update 12 (2): 169–78.
2. Chlebowski R, Kuller L, Prentice R et al. Breast cancer after use of estrogen plus progestinin postmenopausal women. N Engl J Med 2009; 360 (6): 573–87.
3. George J, Colman R, Goldhaber S, Victor J. Marder (2006). Hemostasis and thrombosis: basic principles and clinical practice. Hagerstwon, MD: Lippincott Williams & Wilkins: 1239. ISBN 0781749964.
4. Anderson G, Limacher M, Assaf A, et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA 2004; 291 (14): 1701–12.
5. Manson J, Hsia J, Johnson K, Rossouw J et al. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med 2003; 349 (6): 523–34.
6. Torshin I Yu. Bioinformatics in the post-genomic era: physiology and medicine. Nova Biomedical, ISBN 9781600 217524. 2007.
7. Сухих Г.Т., Торшин И.Ю., Громова О.А. Молекулярные механизмы дидрогестерона (дюфастона). Ч. 1: исследование селективности взаимодействия дидрогестерона с прогестероновыми рецепторами методами молекулярной механики. Гинекология. 2009; 12: 62–7.
8. Торшин И.Ю., Громова О.А., Сухих Г.Т. Молекулярные механизмы дидрогестерона (дюфастона). Ч. 2: полногеномное исследование транскрипционных эффектов рецепторов прогестерона, андрогенов и эстрогенов. Гинекология. 2010; 1: 6–12.
9. Торшин И.Ю., Громова О.А. 25 мгновений молекулярной фармакологии: о развитии клинико-фармакологического мышления. А-Гриф, 2011.
10. Torshin I.Yu.. Bioinformatics in the Post-Genomic Era: The Role of Biophysics, 2006 Nova Biomedical Books, NY, ISBN: 1-60021-048.
11. Torshin IY. Computed energetics of nucleotides in spatial ribozyme structures: an accurate identification of functional regions from structure. ScientificWorldJournal 2004; 26 (4): 228–47.
12. Gadkar-Sable S, Shah C, Rosario G et al. Progesterone receptors: various forms and functions in reproductive tissues. Front Biosci 2005; 10: 2118–30.
13. Schindler A, Campagnoli C, Druckmann R et al. Classification and pharmacology of progestins. Maturitas 2003; 46 (l): 7–16.
14. van Amsterdam PH, Overmars H, Scherpenisse PM et al. Dydrogesterone: Metabolism in man. Eur J Drug Metab Pharmacokinet 1980; 5: 173–84.
15. Schindler A, Campagnoli C, Druckmann R et al.Classification and pharmacology of progestins. Maturitas 2008; 61 (1–2): 171–80.
16. Escande A, Servant N, Rabenoelina F et al. Regulation of activities of steroid hormone receptors by tibolone and its primary metabolites. J Steroid Biochem Mol Biol 2009; 116 (1–2): 8–14.
17. Al Kadri H, Hassan S, Al-Fozan H, Hajeer A. Hormone therapy for endometriosis and surgical menopause. Cochrane Database Syst Rev 2009; 1: CD005997.
18. Garefalakis M, Hickey M. Role of androgens, progestins and tibolone in the treatment of menopausal symptoms: a review of the clinical evidence. Clin Interv Aging 2008; 3 (1): 1–8.
19. Lazovic G, Radivojevic U, Marinkovic J. Tibolone: the way to beat many a postmenopausal ailments. Expert Opin Pharmacother 2008; 9 (6): 1039–47.
20. Dӧren M, Rübig A, Coelingh Bennink H, Holzgreve W. Differential effects on the androgen status of postmenopausal women treated with tibolone and continuous combined estradiol and norethindrone acetate replacement therapy. Fertil Steril 2001; 75 (3): 554–9.
21. Raobaikady B, Parsons M, Reed M, Purohit A. Tibolone and its delta-4, 7alpha-methyl norethisterone metabolite are reversible inhibitors of human aromatase. J Steroid Biochem Mol Biol 2007; 104 (3–5): 154–60.
22. Krattenmacher R. Drospirenone: pharmacology and pharmacokinetics of a unique progestogen. Contraception 2000; 62 (1): 29–38.
23. Pullen M, Laping N, Edwards R, Bray J. Determination of conformational changes in the progesterone receptor using ELISA-like assays. Steroids 2006; 71 (9): 792–8.
24. Edgren R, Stanczyk F. Nomenclature of the gonane progestins. Contraception 60 (6): 313.
25. Sitruk-Ware R. New progestagens for contraceptive use. Hum Reprod Update 12 (2): 169–78.
________________________________________________
1. Rossouw J, Anderson G, Prentice R et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA 2002; 288 (3): 321–33.
2. Chlebowski R, Kuller L, Prentice R et al. Breast cancer after use of estrogen plus progestinin postmenopausal women. N Engl J Med 2009; 360 (6): 573–87.
3. George J, Colman R, Goldhaber S, Victor J. Marder (2006). Hemostasis and thrombosis: basic principles and clinical practice. Hagerstwon, MD: Lippincott Williams & Wilkins: 1239. ISBN 0781749964.
4. Anderson G, Limacher M, Assaf A, et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA 2004; 291 (14): 1701–12.
5. Manson J, Hsia J, Johnson K, Rossouw J et al. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med 2003; 349 (6): 523–34.
6. Torshin I Yu. Bioinformatics in the post-genomic era: physiology and medicine. Nova Biomedical, ISBN 9781600 217524. 2007.
7. Сухих Г.Т., Торшин И.Ю., Громова О.А. Молекулярные механизмы дидрогестерона (дюфастона). Ч. 1: исследование селективности взаимодействия дидрогестерона с прогестероновыми рецепторами методами молекулярной механики. Гинекология. 2009; 12: 62–7.
8. Торшин И.Ю., Громова О.А., Сухих Г.Т. Молекулярные механизмы дидрогестерона (дюфастона). Ч. 2: полногеномное исследование транскрипционных эффектов рецепторов прогестерона, андрогенов и эстрогенов. Гинекология. 2010; 1: 6–12.
9. Торшин И.Ю., Громова О.А. 25 мгновений молекулярной фармакологии: о развитии клинико-фармакологического мышления. А-Гриф, 2011.
10. Torshin I.Yu.. Bioinformatics in the Post-Genomic Era: The Role of Biophysics, 2006 Nova Biomedical Books, NY, ISBN: 1-60021-048.
11. Torshin IY. Computed energetics of nucleotides in spatial ribozyme structures: an accurate identification of functional regions from structure. ScientificWorldJournal 2004; 26 (4): 228–47.
12. Gadkar-Sable S, Shah C, Rosario G et al. Progesterone receptors: various forms and functions in reproductive tissues. Front Biosci 2005; 10: 2118–30.
13. Schindler A, Campagnoli C, Druckmann R et al. Classification and pharmacology of progestins. Maturitas 2003; 46 (l): 7–16.
14. van Amsterdam PH, Overmars H, Scherpenisse PM et al. Dydrogesterone: Metabolism in man. Eur J Drug Metab Pharmacokinet 1980; 5: 173–84.
15. Schindler A, Campagnoli C, Druckmann R et al.Classification and pharmacology of progestins. Maturitas 2008; 61 (1–2): 171–80.
16. Escande A, Servant N, Rabenoelina F et al. Regulation of activities of steroid hormone receptors by tibolone and its primary metabolites. J Steroid Biochem Mol Biol 2009; 116 (1–2): 8–14.
17. Al Kadri H, Hassan S, Al-Fozan H, Hajeer A. Hormone therapy for endometriosis and surgical menopause. Cochrane Database Syst Rev 2009; 1: CD005997.
18. Garefalakis M, Hickey M. Role of androgens, progestins and tibolone in the treatment of menopausal symptoms: a review of the clinical evidence. Clin Interv Aging 2008; 3 (1): 1–8.
19. Lazovic G, Radivojevic U, Marinkovic J. Tibolone: the way to beat many a postmenopausal ailments. Expert Opin Pharmacother 2008; 9 (6): 1039–47.
20. Dӧren M, Rübig A, Coelingh Bennink H, Holzgreve W. Differential effects on the androgen status of postmenopausal women treated with tibolone and continuous combined estradiol and norethindrone acetate replacement therapy. Fertil Steril 2001; 75 (3): 554–9.
21. Raobaikady B, Parsons M, Reed M, Purohit A. Tibolone and its delta-4, 7alpha-methyl norethisterone metabolite are reversible inhibitors of human aromatase. J Steroid Biochem Mol Biol 2007; 104 (3–5): 154–60.
22. Krattenmacher R. Drospirenone: pharmacology and pharmacokinetics of a unique progestogen. Contraception 2000; 62 (1): 29–38.
23. Pullen M, Laping N, Edwards R, Bray J. Determination of conformational changes in the progesterone receptor using ELISA-like assays. Steroids 2006; 71 (9): 792–8.
24. Edgren R, Stanczyk F. Nomenclature of the gonane progestins. Contraception 60 (6): 313.
25. Sitruk-Ware R. New progestagens for contraceptive use. Hum Reprod Update 12 (2): 169–78.
Авторы
И.Ю.Торшин1, О.А.Громова1, 2, К.В.Рудаков3
1. Российский сателлитный Центр международного института микроэлементов ЮНЕСКО, Москва;
2. ГОУ ВПО Ивановская государственная медицинская академия Минздравсоцразвития РФ;
3. Вычислительный центр РАН им. А.А.Дородницына, Москва
1. Российский сателлитный Центр международного института микроэлементов ЮНЕСКО, Москва;
2. ГОУ ВПО Ивановская государственная медицинская академия Минздравсоцразвития РФ;
3. Вычислительный центр РАН им. А.А.Дородницына, Москва
________________________________________________
I.Ju.Torshin1, O.A.Gromova1, 2, K.V.Rudakov3
1. Russian satellite Center of the International Institute of Microelements of UNESCO, Moscow
2. Ivanovo State medical academy of the Ministry of Public Health and social development of the Russian Federation
3. A.A.Dorodnitsyn Computer centre of the Russian Academy of Sciences, Moscow
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