Π”ΠΈΠΏΠ»ΠΎΠΌ, курсовая, ΠΊΠΎΠ½Ρ‚Ρ€ΠΎΠ»ΡŒΠ½Π°Ρ Ρ€Π°Π±ΠΎΡ‚Π°
ΠŸΠΎΠΌΠΎΡ‰ΡŒ Π² написании студСнчСских Ρ€Π°Π±ΠΎΡ‚

РСгуляторноС дСйствиС 17 ?-эстрадиола ΠΈ 1, 25-дигидроксивитамина D3 Π² ΠΊΠ»Π΅Ρ‚ΠΊΠ°Ρ… Π½Π΅ΠΊΠΎΡ‚ΠΎΡ€Ρ‹Ρ… Ρ€Π°ΠΊΠΎΠ²Ρ‹Ρ… Π»ΠΈΠ½ΠΈΠΉ

Π”ΠΈΡΡΠ΅Ρ€Ρ‚Π°Ρ†ΠΈΡΠŸΠΎΠΌΠΎΡ‰ΡŒ Π² Π½Π°ΠΏΠΈΡΠ°Π½ΠΈΠΈΠ£Π·Π½Π°Ρ‚ΡŒ ΡΡ‚ΠΎΠΈΠΌΠΎΡΡ‚ΡŒΠΌΠΎΠ΅ΠΉ Ρ€Π°Π±ΠΎΡ‚Ρ‹

Π Π°ΠΊΠΈ ΠΌΠΎΠ»ΠΎΡ‡Π½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ‹ Ρ‚Π°ΠΊΠΆΠ΅ ΡΠ²Π»ΡΡŽΡ‚ΡΡ вСсьма частым онкологичСским Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠ΅ΠΌ. Π’ Ρ€Π°Π·Π²ΠΈΡ‚Ρ‹Ρ… странах Ρ€Π°ΠΊ ΠΌΠΎΠ»ΠΎΡ‡Π½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ‹ Π·Π°Π½ΠΈΠΌΠ°Π΅Ρ‚ ΠΏΠ΅Ρ€Π²ΠΎΠ΅ ΠΈΠ»ΠΈ Π²Ρ‚ΠΎΡ€ΠΎΠ΅ мСсто ΠΏΠΎ Ρ‡Π°ΡΡ‚ΠΎΡ‚Π΅ онкологичСских Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ Ρƒ ΠΆΠ΅Π½Ρ‰ΠΈΠ½ (20βˆ’25% всСх случаСв) (Π’Ρ€Π°ΠΏΠ΅Π·Π½ΠΈΠΊΠΎΠ², Π­ΠΊΡ…Π°Ρ€Π΄Ρ‚, 1981). Π’ ΠΏΡ€ΠΎΡ‚ΠΈΠ²ΠΎΠΏΠΎΠ»ΠΎΠΆΠ½ΠΎΡΡ‚ΡŒ l, 25(OH)2D3, 17Ρ€-эстрадиол стимулируСт процСссы Π²ΠΎ ΠΌΠ½ΠΎΠ³ΠΈΡ… Ρ€Π°ΠΊΠΎΠ²Ρ‹Ρ… ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½Ρ‹Ρ… линиях, Π² ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎΡΡ‚ΠΈ ΠΏΡ€ΠΈ Ρ€Π°ΠΊΠ΅ ΠΌΠΎΠ»ΠΎΡ‡Π½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ‹… Π§ΠΈΡ‚Π°Ρ‚ΡŒ Π΅Ρ‰Ρ‘ >

Π‘ΠΎΠ΄Π΅Ρ€ΠΆΠ°Π½ΠΈΠ΅

  • Π“Π»Π°Π²Π° 1. ΠžΠ‘Π—ΠžΠ  Π›Π˜Π’Π•Π ΠΠ’Π£Π Π«
    • 1. 1. ЭстрогСновый Ρ€Π΅Ρ†Π΅ΠΏΡ‚ΠΎΡ€ ΠΈ Π΄Π΅ΠΉΡΡ‚Π²ΠΈΠ΅ 17(3-эстрадиола
    • 1. 2. Π’ΠΈΡ‚Π°ΠΌΠΈΠ½ D3 ΠΈ Π΅Π³ΠΎ Ρ€Π΅Ρ†Π΅ΠΏΡ‚ΠΎΡ€
    • 1. 3. Π“Π΅Π½ Ρ„Π°ΠΊΡ‚ΠΎΡ€Π° роста ΠΊΠ΅Ρ€Π°Ρ‚ΠΈΠ½ΠΎΡ†ΠΈΡ‚ΠΎΠ² — ΠΏΡ€Π΅Π΄ΡΡ‚Π°Π²ΠΈΡ‚Π΅Π»ΡŒ сСмСйства Π³Π΅Π½ΠΎΠ² Ρ„Π°ΠΊΡ‚ΠΎΡ€ΠΎΠ² роста фибробластов
    • 1. 4. БСмСйство ΠΏΡ€ΠΎΡ‚Π΅ΠΈΠ½-ΠΊΠΈΠ½Π°Π· ΠΈ ΠœΠΠ -ΠΊΠΈΠ½Π°Π·
  • Π“Π»Π°Π²Π° 2. ΠœΠΠ’Π•Π Π˜ΠΠ›Π« И ΠœΠ•Π’ΠžΠ”Π«
    • 2. 1. Π‘Π°ΠΊΡ‚Π΅Ρ€ΠΈΠ°Π»ΡŒΠ½Ρ‹Π΅ ΡˆΡ‚Π°ΠΌΠΌΡ‹ ΠΈ ΠΏΠ»Π°Π·ΠΌΠΈΠ΄Ρ‹
    • 2. 2. ΠšΠ»Π΅Ρ‚ΠΎΡ‡Π½Ρ‹Π΅ ΠΊΡƒΠ»ΡŒΡ‚ΡƒΡ€Ρ‹ ΠΈ Π²Ρ‹Π΄Π΅Π»Π΅Π½ΠΈΠ΅ РНК
    • 2. 3. ΠžΡ†Π΅Π½ΠΊΠ° ΠΏΡ€ΠΎΠ»ΠΈΡ„Π΅Ρ€Π°Ρ‚ΠΈΠ²Π½ΠΎΠΉ способности ΠΊΠ»Π΅Ρ‚ΠΎΠΊ
    • 2. 4. ΠŸΡ€ΠΈΠ³ΠΎΡ‚ΠΎΠ²Π»Π΅Π½ΠΈΠ΅ ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½ΠΎΠ³ΠΎ Π»ΠΈΠ·Π°Ρ‚Π°
    • 2. 5. Π’Ρ‹Π΄Π΅Π»Π΅Π½ΠΈΠ΅ Π±Π΅Π»ΠΊΠ° ΠΈ ΠΈΠΌΠΌΡƒΠ½ΠΎΠΏΡ€Π΅Ρ†ΠΈΠΏΠΈΡ‚ация
    • 2. 6. ΠœΠΈΠΊΡ€ΠΎΡ‡ΠΈΠΏΠΎΠ²Ρ‹ΠΉ Π°Π½Π°Π»ΠΈΠ·
    • 2. 7. ВСстСрн-Π±Π»ΠΎΡ‚-Π°Π½Π°Π»ΠΈΠ·
    • 2. 8. Π Π΅Π²Π΅Ρ€Ρ‚Π°Π·Π½ΠΎ-транскрипционная рСакция
    • 2. 9. ΠšΠΎΠ»ΠΈΡ‡Π΅ΡΡ‚Π²Π΅Π½Π½Π°Ρ полимСразная цСпная рСакция Π² Ρ€Π΅Π°Π»ΡŒΠ½ΠΎΠΌ Π²Ρ€Π΅ΠΌΠ΅Π½ΠΈ
    • 2. 10. ΠšΠ»ΠΎΠ½ΠΈΡ€ΠΎΠ²Π°Π½ΠΈΠ΅ Ρ„Ρ€Π°Π³ΠΌΠ΅Π½Ρ‚Π° Π² ΠΏΠ»Π°Π·ΠΌΠΈΠ΄Π½Ρ‹ΠΉ Π²Π΅ΠΊΡ‚ΠΎΡ€ PGEM-T Easy
    • 2. 11. Π’Ρ‹Π΄Π΅Π»Π΅Π½ΠΈΠ΅ ΠΏΠ»Π°Π·ΠΌΠΈΠ΄Ρ‹
    • 2. 12. БиквСнс
    • 2. 13. Π˜Π·ΠΌΠ΅Ρ€Π΅Π½ΠΈΠ΅ МАР-ΠΊΠΈΠ½Π°Π·Π½ΠΎΠΉ активности
    • 2. 14. ΠœΠ΅Ρ‚ΠΎΠ΄ Π°Π½Π°Π»ΠΈΠ·Π° РНК ΠΏΡ€ΠΈ ΠΏΠΎΠΌΠΎΡ‰ΠΈ Π·Π°Ρ‰ΠΈΡ‚Ρ‹ ΠΎΡ‚ Ρ€Π°ΡΡ‰Π΅ΠΏΠ»Π΅Π½ΠΈΡ РНКазами
    • 2. 15. ΠŸΡ€ΠΎΠ³Ρ€Π°ΠΌΠΌΠ½ΠΎΠ΅ обСспСчСниС ΠΈ Π±Π°Π·Ρ‹ Π΄Π°Π½Π½Ρ‹Ρ…
    • 2. 16. Π Π΅Π°ΠΊΡ‚ΠΈΠ²Ρ‹ ΠΈ ΠΌΠ°Ρ‚Π΅Ρ€ΠΈΠ°Π»Ρ‹
  • Π“Π»Π°Π²Π° 3. РЕЗУЛЬВАВЫ
    • 3. 1. ИсслСдованиС рСгуляции Π³Π΅Π½Π°
  • /"17Π -эстрадиолом ΠΈ 1,25-дигидроксивитамином D
    • 3. 1. 1. ИсслСдованиС экспрСссии Ρ€Π΅Ρ†Π΅ΠΏΡ‚ΠΎΡ€Π° Π²ΠΈΡ‚Π°ΠΌΠΈΠ½Π° D3 Π² ΠΊΠ»Π΅Ρ‚ΠΊΠ°Ρ… Π»ΠΈΠ½ΠΈΠΈ MCF
    • 3. 1. 2. ΠšΠΎΠΌΠΏΡŒΡŽΡ‚Π΅Ρ€Π½Ρ‹ΠΉ Π°Π½Π°Π»ΠΈΠ· ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°Ρ‚Π΅Π»ΡŒΠ½ΠΎΡΡ‚Π΅ΠΉ Π² 5"-Ρ„Π»Π°Π½ΠΊΠΈΡ€ΡƒΡŽΡ‰Π΅ΠΉ области Π³Π΅Π½Π° kgf
    • 3. 1. 3. ИсслСдованиС дСйствия 1,25-дигидроксивитамина D3 ΠΏΡ€ΠΈ ΠΏΠΎΠΌΠΎΡ‰ΠΈ ΠΌΠ΅Ρ‚ΠΎΠ΄Π° ΠΌΠΈΠΊΡ€ΠΎΡ‡ΠΈΠΏΠΎΠ²ΠΎΠ³ΠΎ Π°Π½Π°Π»ΠΈΠ·Π°
    • 3. 1. 4. ΠžΡ†Π΅Π½ΠΊΠ° ΠΌΠ΅Ρ‚ΠΎΠ΄ΠΎΠΌ количСствСнной ПНР ΠΏΡ€ΠΎΠ΄ΡƒΠΊΡ†ΠΈΠΈ РНК Π³Π΅Π½ΠΎΠΌ kgf ΠΏΠΎΠ΄ воздСйствиСм 1,25-дигидроксивитамина D3 ΠΈ 17Π -эстрадиола
    • 3. 1. 5. ВСстСрн-Π±Π»ΠΎΡ‚-Π°Π½Π°Π»ΠΈΠ· ΡƒΡ€ΠΎΠ²Π½Π΅ΠΉ экспрСссии Π³Π΅Π½Π° kgf Π² ΠΊΠ»Π΅Ρ‚ΠΊΠ°Ρ… Π»ΠΈΠ½ΠΈΠΉ MCF7 ΠΈ LNCaP
    • 3. 2. ВлияниС 1,25-дигидроксивитамина D3 ΠΈ 17(3-эстрадиола Π½Π° ΠΏΡ€ΠΎΠ»ΠΈΡ„Π΅Ρ€Π°Ρ†ΠΈΡŽ исслСдуСмых Ρ€Π°ΠΊΠΎΠ²Ρ‹Ρ… ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½Ρ‹Ρ… Π»ΠΈΠ½ΠΈΠΉ ΠΈ ΡΠ»Π΅ΠΌΠ΅Π½Ρ‚Ρ‹ МАР-ΠΊΠΈΠ½Π°Π·Π½ΠΎΠ³ΠΎ каскада
    • 3. 2. 1. ΠŸΡ€ΠΎΠ»ΠΈΡ„Π΅Ρ€Π°Ρ†ΠΈΡ ΠΊΠ»Π΅Ρ‚ΠΎΠΊ Π»ΠΈΠ½ΠΈΠΉ MCF7 ΠΈ LNCaP возрастаСт ΠΏΠΎΠ΄ воздСйствиСм 17Ρ€-эстрадиола ΠΈ Ρ‚ормозится ΠΏΠΎΠ΄ воздСйствиСм 1,25-дигидроксивитамина D
    • 3. 2. 2. ΠšΡ€Π°Ρ‚ΠΊΠΎΠ²Ρ€Π΅ΠΌΠ΅Π½Π½Ρ‹Π΅ воздСйствия 17(3-эстрадиола ΠΈ 1,25-дигидроксивитамина D3 Π°ΠΊΡ‚ΠΈΠ²ΠΈΡ€ΡƒΡŽΡ‚ МАР-ΠΊΠΈΠ½Π°Π·Ρ‹ Π² ΠΊΠ»Π΅Ρ‚ΠΊΠ°Ρ…
  • MCF7 ΠΈ LNCaP
    • 3. 2. 3. Π”Π»ΠΈΡ‚Π΅Π»ΡŒΠ½ΠΎΠ΅ воздСйствиС 1,25-дигидроксивитамина D3 подавляСт 17Π -эстрадиол-Π·Π°Π²ΠΈΡΠΈΠΌΡƒΡŽ Π°ΠΊΡ‚ΠΈΠ²Π°Ρ†ΠΈΡŽ МАР-ΠΊΠΈΠ½Π°Π· Π² ΠΊΠ»Π΅Ρ‚ΠΊΠ°Ρ… Π»ΠΈΠ½ΠΈΠΈΠΈ LNCaP
  • ΠžΠ‘Π‘Π£Π–Π”Π•ΠΠ˜Π•
  • Π’Π«Π’ΠžΠ”Π«

РСгуляторноС дСйствиС 17 ?-эстрадиола ΠΈ 1, 25-дигидроксивитамина D3 Π² ΠΊΠ»Π΅Ρ‚ΠΊΠ°Ρ… Π½Π΅ΠΊΠΎΡ‚ΠΎΡ€Ρ‹Ρ… Ρ€Π°ΠΊΠΎΠ²Ρ‹Ρ… Π»ΠΈΠ½ΠΈΠΉ (Ρ€Π΅Ρ„Π΅Ρ€Π°Ρ‚, курсовая, Π΄ΠΈΠΏΠ»ΠΎΠΌ, ΠΊΠΎΠ½Ρ‚Ρ€ΠΎΠ»ΡŒΠ½Π°Ρ)

Π›ΠΈΠ³Π°Π½Π΄Ρ‹ ядСрных Ρ€Π΅Ρ†Π΅ΠΏΡ‚ΠΎΡ€ΠΎΠ² — это нСбольшиС Π»ΠΈΠΏΠΎΡ„ΠΈΠ»ΡŒΠ½Ρ‹Π΅ ΠΌΠΎΠ»Π΅ΠΊΡƒΠ»Ρ‹, ΠΊΠΎΡ‚ΠΎΡ€Ρ‹Π΅ бСспрСпятствСнно ΠΏΡ€ΠΎΠ½ΠΈΠΊΠ°ΡŽΡ‚ Ρ‡Π΅Ρ€Π΅Π· ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½ΡƒΡŽ ΠΈ ΡΠ΄Π΅Ρ€Π½ΡƒΡŽ ΠΌΠ΅Π±Ρ€Π°Π½Ρ‹, ΠΈ ΡΠ²ΡΠ·Ρ‹Π²Π°ΡŽΡ‚ся со ΡΠ²ΠΎΠΈΠΌΠΈ Ρ€Π΅Ρ†Π΅ΠΏΡ‚ΠΎΡ€Π°ΠΌΠΈ, Π»ΠΎΠΊΠ°Π»ΠΈΠ·ΠΎΠ²Π°Π½Π½Ρ‹ΠΌΠΈ Π² ΡΠ΄Ρ€Π΅ ΠΊΠ»Π΅Ρ‚ΠΊΠΈ (Beato et al., 1995; Mangelsdorf et al., 1995; Perlman, Evans- 1997). Π›ΠΈΠ³Π°Π½Π΄, ΡΠ²ΡΠ·Ρ‹Π²Π°ΡΡΡŒ с Π±Π΅Π»ΠΊΠΎΠΌ (ядСрным Ρ€Π΅Ρ†Π΅ΠΏΡ‚ΠΎΡ€ΠΎΠΌ), ΠΏΠ΅Ρ€Π΅Π²ΠΎΠ΄ΠΈΡ‚ Π΅Π³ΠΎ Π² Π°ΠΊΡ‚ΠΈΠ²Π½ΡƒΡŽ Ρ„ΠΎΡ€ΠΌΡƒ (Sone et al., 1989; Hughes et al., 1991). АктивированныС ядСрныС Ρ€Π΅Ρ†Π΅ΠΏΡ‚ΠΎΡ€Ρ‹, ΠΊΠ°ΠΊ Π² Ρ„ΠΎΡ€ΠΌΠ΅ ΠΌΠΎΠ½ΠΎΠΌΠ΅Ρ€Π½Ρ‹Ρ…, Ρ‚Π°ΠΊ ΠΈ Π΄ΠΈΠΌΠ΅Ρ€Π½Ρ‹Ρ… структур, ΠΏΡ€ΠΈΠΎΠ±Ρ€Π΅Ρ‚Π°ΡŽΡ‚ ΡΠΏΠΎΡΠΎΠ±Π½ΠΎΡΡ‚ΡŒ ΡΠ²ΡΠ·Ρ‹Π²Π°Ρ‚ΡŒΡΡ с ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°Ρ‚Π΅Π»ΡŒΠ½ΠΎΡΡ‚ΡΠΌΠΈ Π”ΠΠš, ΠΈΠΌΠ΅ΡŽΡ‰ΠΈΠΌΠΈ Π² ΡΠ²ΠΎΠ΅ΠΌ составС ΠΏΠΎΠ΄ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°Ρ‚Π΅Π»ΡŒΠ½ΠΎΡΡ‚ΡŒ AGGTCA ΠΈ Π΅Π΅ Π²Π°Ρ€ΠΈΠ°Ρ†ΠΈΠΈ, Ρ…Π°Ρ€Π°ΠΊΡ‚Π΅Ρ€Π½Ρ‹Π΅ для ΠΏΡ€ΠΎΠΌΠΎΡ‚ΠΎΡ€ΠΎΠ² Π³Π΅Π½ΠΎΠ² (Umensono et al., 1991; Mangelsdorf et al., 1995). Π’Π°ΠΊΠΎΠ³ΠΎ Ρ€ΠΎΠ΄Π° элСмСнты Π»ΠΎΠΊΠ°Π»ΠΈΠ·ΠΎΠ²Π°Π½Ρ‹ Π² ΠΈΠ½Ρ‚Ρ€ΠΎΠ½Π°Ρ… ΠΈ 5'- Ρ„Π»Π°Π½ΠΊΠΈΡ€ΡƒΡŽΡ‰ΠΈΡ… областях Π³Π΅Π½ΠΎΠ² (Koop, Hood, 1994). ПослС связывания ядСрных Ρ€Π΅Ρ†Π΅ΠΏΡ‚ΠΎΡ€ΠΎΠ² с Π”ΠΠš, ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ ΡƒΡ€ΠΎΠ²Π½Π΅ΠΉ транскрипции мРНК происходит Π·Π° ΡΡ‡Π΅Ρ‚ прямого ΠΈΠ»ΠΈ опосрСдованного Π±Π΅Π»ΠΎΠΊ-Π±Π΅Π»ΠΊΠΎΠ²ΠΎΠ³ΠΎ взаимодСйствия с Ρ‚ранскрипционным комплСксом, Π² Ρ€Π΅Π·ΡƒΠ»ΡŒΡ‚Π°Ρ‚Π΅ Ρ‡Π΅Π³ΠΎ происходит ΡƒΠ²Π΅Π»ΠΈΡ‡Π΅Π½ΠΈΠ΅ ΠΈΠ»ΠΈ ΡƒΠΌΠ΅Π½ΡŒΡˆΠ΅Π½ΠΈΠ΅ ΡƒΡ€ΠΎΠ²Π½Π΅ΠΉ транскрипции мРНК ΠΈ, соотвСтствСнно, ΠΏΡ€ΠΎΠ΄ΡƒΠΊΡ†ΠΈΠΈ Π±Π΅Π»ΠΊΠ°, ΠΊΠΎΠ΄ΠΈΡ€ΡƒΠ΅ΠΌΠΎΠ³ΠΎ Ρ‚Π΅ΠΌ ΠΈΠ»ΠΈ ΠΈΠ½Ρ‹ΠΌ Π³Π΅Π½ΠΎΠΌ Π² ΠΊΠ»Π΅Ρ‚ΠΊΠ΅ (Gronemeyer, Laudet, 1995; Mangelsdorf et al., 1995). ВсС ядСрныС Ρ€Π΅Ρ†Π΅ΠΏΡ‚ΠΎΡ€Ρ‹ ΠΈΠΌΠ΅ΡŽΡ‚ ΡΡ…ΠΎΠΆΡƒΡŽ Π΄ΠΎΠΌΠ΅Π½Π½ΡƒΡŽ структуру Π±Π΅Π»ΠΊΠΎΠ²ΠΎΠΉ ΠΌΠΎΠ»Π΅ΠΊΡƒΠ»Ρ‹ ΠΈ ΠΏΠΎ ΡΡ‚ΠΎΠΌΡƒ ΠΏΡ€ΠΈΠ·Π½Π°ΠΊΡƒ ΠΎΠ±ΡŠΠ΅Π΄ΠΈΠ½Π΅Π½Ρ‹ Π² ΠΎΠ΄Π½ΠΎ сСмСйство (Mangelsdorf et al., 1995).

Π˜Π·ΡƒΡ‡Π΅Π½ΠΈΠ΅ процСссов ΠΈ ΠΌΠ΅Ρ…Π°Π½ΠΈΠ·ΠΌΠΎΠ² влияния Π»ΠΈΠ³Π°Π½Π΄ΠΎΠ² ядСрных Ρ€Π΅Ρ†Π΅ΠΏΡ‚ΠΎΡ€ΠΎΠ² ΠΈ ΡΠ°ΠΌΠΈΡ… Π±Π΅Π»ΠΊΠΎΠ² этих Ρ€Π΅Ρ†Π΅ΠΏΡ‚ΠΎΡ€ΠΎΠ² Π½Π° Ρ€Π΅Π³ΡƒΠ»ΡΡ‚ΠΎΡ€Π½Ρ‹Π΅ каскады ΠΈ Ρ‚Ρ€Π°Π½ΡΠΊΡ€ΠΈΠΏΡ†ΠΈΡŽ Π³Π΅Π½ΠΎΠ² являСтся Π²Π°ΠΆΠ½Ρ‹ΠΌ Π½Π°ΠΏΡ€Π°Π²Π»Π΅Π½ΠΈΠ΅ΠΌ Π² ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡΡ… ΠΊΠ°Π½Ρ†Π΅Ρ€ΠΎΠ³Π΅Π½Π΅Π·Π°. Одним ΠΈΠ· ΠΊΠ»ΡŽΡ‡Π΅Π²Ρ‹Ρ… элСмСнтов Π² Ρ€Π΅Π³ΡƒΠ»ΡΡ†ΠΈΠΈ этих процСссов являСтся взаимодСйствиС ядСрных Ρ€Π΅Ρ†Π΅ΠΏΡ‚ΠΎΡ€ΠΎΠ² с ΠΎΠΏΡ€Π΅Π΄Π΅Π»Π΅Π½Π½Ρ‹ΠΌΠΈ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°Ρ‚Π΅Π»ΡŒΠ½ΠΎΡΡ‚ΡΠΌΠΈ Π”ΠΠš, Π½Π°Π·Ρ‹Π²Π°Π΅ΠΌΡ‹ΠΌΠΈ Π³ΠΎΡ€ΠΌΠΎΠ½-Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡ‚Π²ΡƒΡŽΡ‰ΠΈΠΌΠΈ элСмСнтами (HRE) (Pabo, Sauer, 1994).

Одним ΠΈΠ· ΠΏΠΎΠ΄Ρ…ΠΎΠ΄ΠΎΠ² ΠΊ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠ½ΠΎΠΉ Ρ‚Π΅Ρ€Π°ΠΏΠΈΠΈ онкологичСских Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ являСтся использованиС Π³ΠΎΡ€ΠΌΠΎΠ½ΠΎΠ² ΠΈ Π³ΠΎΡ€ΠΌΠΎΠ½ΠΎΠΏΠΎΠ΄ΠΎΠ±Π½Ρ‹Ρ… соСдинСний, Π° Ρ‚Π°ΠΊΠΆΠ΅ соСдинСний, ΠΈΡ… ΠΈΠ½Π³ΠΈΠ±ΠΈΡ€ΡƒΡŽΡ‰ΠΈΡ…, для подавлСния ΠΏΡ€ΠΎΠ»ΠΈΡ„Π΅Ρ€Π°Ρ†ΠΈΠΈ Ρ€Π°ΠΊΠΎΠ²Ρ‹Ρ… ΠΊΠ»Π΅Ρ‚ΠΎΠΊ посрСдством ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠΉ Π² Ρ€Π΅Π³ΡƒΠ»ΡΡ‚ΠΎΡ€Π½Ρ‹Ρ… путях ΠΈ ΡƒΡ€ΠΎΠ²Π½ΡΡ… транскрипции Π³Π΅Π½ΠΎΠ² с ΠΏΠΎΠΌΠΎΡ‰ΡŒΡŽ Π»ΠΈΠ³Π°Π½Π΄ΠΎΠ² Π±Π΅Π»ΠΊΠΎΠ² ядСрных Ρ€Π΅Ρ†Π΅ΠΏΡ‚ΠΎΡ€ΠΎΠ² (Resche-Rigon, Gronemeyer, 1998).

Π’ Π΄Π°Π½Π½ΠΎΠΉ Ρ€Π°Π±ΠΎΡ‚Π΅ ΠΈΡΡΠ»Π΅Π΄ΡƒΡŽΡ‚ΡΡ Π½Π΅ΠΊΠΎΡ‚ΠΎΡ€Ρ‹Π΅ аспСкты Π³Π΅Π½ΠΎΠΌΠ½ΠΎΠ³ΠΎ ΠΈ Π½Π΅ Π³Π΅Π½ΠΎΠΌΠ½ΠΎΠ³ΠΎ дСйствия Π»ΠΈΠ³Π°Π½Π΄ΠΎΠ² ядСрных Ρ€Π΅Ρ†Π΅ΠΏΡ‚ΠΎΡ€ΠΎΠ² — 17Π ~эстрадиола ΠΈ 1,25-дигидроксивитамина D3 (l, 25(OH)2D3) Π² ΠΊΠ»Π΅Ρ‚ΠΊΠ°Ρ… Π»ΠΈΠ½ΠΈΠΉ LNCaP ΠΈ MCF7 (соотвСтствСнно, Ρ€Π°ΠΊΠ° простаты ΠΈ Ρ€Π°ΠΊΠ° ΠΌΠΎΠ»ΠΎΡ‡Π½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ‹).

Π Π°ΠΊ простаты являСтся ΠΎΠ΄Π½ΠΈΠΌ ΠΈΠ· Π½Π°ΠΈΠ±ΠΎΠ»Π΅Π΅ распространСнных злокачСствСнных Π½ΠΎΠ²ΠΎΠΎΠ±Ρ€Π°Π·ΠΎΠ²Π°Π½ΠΈΠΉ Ρƒ ΠΌΡƒΠΆΡ‡ΠΈΠ½ ΠΈ ΡΡ‚ΠΎΠΈΡ‚ Π½Π° Π²Ρ‚ΠΎΡ€ΠΎΠΌ мСстС послС Ρ€Π°ΠΊΠ° Π»Π΅Π³ΠΊΠΈΡ… Π² Ρ€ΡΠ΄Ρƒ ΠΏΡ€ΠΈΡ‡ΠΈΠ½ смСртности Π² Ρ€Π΅Π·ΡƒΠ»ΡŒΡ‚Π°Ρ‚Π΅ онкологичСских Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ (Ficazzola, Taneja, 1997). Π‘Ρ‹Π»Π° ΠΏΠΎΠΊΠ°Π·Π°Π½Π° коррСляция уровня Π²ΠΈΡ‚Π°ΠΌΠΈΠ½Π° D3 Π² ΡΡ‹Π²ΠΎΡ€ΠΎΡ‚ΠΊΠ΅ ΠΊΡ€ΠΎΠ²ΠΈ с Ρ€ΠΈΡΠΊΠΎΠΌ заболСвания Ρ€Π°ΠΊΠΎΠΌ ΠΏΡ€Π΅Π΄ΡΡ‚Π°Ρ‚Π΅Π»ΡŒΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ‹: ΠΌΡƒΠΆΡ‡ΠΈΠ½Ρ‹ с ΠΏΠΎΠ½ΠΈΠΆΠ΅Π½Π½Ρ‹ΠΌ ΡƒΡ€ΠΎΠ²Π½Π΅ΠΌ Π²ΠΈΡ‚Π°ΠΌΠΈΠ½Π° D3 (Π½ΠΈΠΆΠ΅ 50 Π½ΠΌ/Π») ΠΈΠΌΠ΅ΡŽΡ‚ Π² 1.7 Ρ€Π°Π·Π° больший риск заболСвания Ρ€Π°ΠΊΠΎΠΌ простаты ΠΏΠΎ ΡΡ€Π°Π²Π½Π΅Π½ΠΈΡŽ с ΠΌΡƒΠΆΡ‡ΠΈΠ½Π°ΠΌΠΈ, Ρƒ ΠΊΠΎΡ‚ΠΎΡ€Ρ‹Ρ… ΡƒΡ€ΠΎΠ²Π΅Π½ΡŒ 25-дигидроксивитамина D3 Π²Ρ‹ΡˆΠ΅ срСднСго (Frick et al., 1987; Tuohimaa et al., 2001).

Π Π°ΠΊΠΈ ΠΌΠΎΠ»ΠΎΡ‡Π½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ‹ Ρ‚Π°ΠΊΠΆΠ΅ ΡΠ²Π»ΡΡŽΡ‚ΡΡ вСсьма частым онкологичСским Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠ΅ΠΌ. Π’ Ρ€Π°Π·Π²ΠΈΡ‚Ρ‹Ρ… странах Ρ€Π°ΠΊ ΠΌΠΎΠ»ΠΎΡ‡Π½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ‹ Π·Π°Π½ΠΈΠΌΠ°Π΅Ρ‚ ΠΏΠ΅Ρ€Π²ΠΎΠ΅ ΠΈΠ»ΠΈ Π²Ρ‚ΠΎΡ€ΠΎΠ΅ мСсто ΠΏΠΎ Ρ‡Π°ΡΡ‚ΠΎΡ‚Π΅ онкологичСских Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ Ρƒ ΠΆΠ΅Π½Ρ‰ΠΈΠ½ (20−25% всСх случаСв) (Π’Ρ€Π°ΠΏΠ΅Π·Π½ΠΈΠΊΠΎΠ², Π­ΠΊΡ…Π°Ρ€Π΄Ρ‚, 1981). Π’ ΠΏΡ€ΠΎΡ‚ΠΈΠ²ΠΎΠΏΠΎΠ»ΠΎΠΆΠ½ΠΎΡΡ‚ΡŒ l, 25(OH)2D3, 17Ρ€-эстрадиол стимулируСт процСссы Π²ΠΎ ΠΌΠ½ΠΎΠ³ΠΈΡ… Ρ€Π°ΠΊΠΎΠ²Ρ‹Ρ… ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½Ρ‹Ρ… линиях, Π² ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎΡΡ‚ΠΈ ΠΏΡ€ΠΈ Ρ€Π°ΠΊΠ΅ ΠΌΠΎΠ»ΠΎΡ‡Π½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ‹, ΠΈ ΠΏΠΎΠ΄Π°Π²Π»Π΅Π½ΠΈΠ΅ Π΅Π³ΠΎ активности с ΠΏΠΎΠΌΠΎΡ‰ΡŒΡŽ Ρ€Π°Π·Π»ΠΈΡ‡Π½Ρ‹Ρ… ΠΌΠ΅Ρ‚ΠΎΠ΄ΠΎΠ², срСди ΠΊΠΎΡ‚ΠΎΡ€Ρ‹Ρ… сущСствСнноС мСсто Π·Π°Π½ΠΈΠΌΠ°Π΅Ρ‚ ΠΏΡ€ΠΈΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ антиэстрогСнов, способствуСт замСдлСнию роста Π³ΠΎΡ€ΠΌΠΎΠ½-зависимых ΠΎΠΏΡƒΡ…ΠΎΠ»Π΅ΠΉ (Santen et al., 1990). Π’ΠΏΠ΅Ρ€Π²Ρ‹Π΅ эффСкт 17(3-эстрадиола Π±Ρ‹Π» описан Π² Ρ€Π°Π±ΠΎΡ‚Π΅ Π›ΠΈΠΏΠΏΠΌΠ°Π½Π° ΠΈ Π‘ΠΎΠ»Π°Π½Π° (Lippman, Bolan, 1975). Π­Ρ‚ΠΈ Π°Π²Ρ‚ΠΎΡ€Ρ‹ ΠΏΠΎΠΊΠ°Π·Π°Π»ΠΈ, Ρ‡Ρ‚ΠΎ ΠΏΠΎΠ΄Π°Π²Π»Π΅Π½Π½Ρ‹ΠΉ антиэстрогСном тамоксифСном рост ΠΊΠ»Π΅Ρ‚ΠΎΠΊ Π»ΠΈΠ½ΠΈΠΈ MCF7 — Ρ€Π°ΠΊΠ° ΠΌΠΎΠ»ΠΎΡ‡Π½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ‹ (эстрогСн-Ρ€Π΅Ρ†Π΅ΠΏΡ‚ΠΎΡ€ ΠΏΠΎΠ·ΠΈΡ‚ΠΈΠ²Π½ΠΎΠΉ) возобновлялся ΠΏΡ€ΠΈ Π΄ΠΎΠ±Π°Π²Π»Π΅Π½ΠΈΠΈ 17[3-эстрадиола. Π‘ Ρ‚Π΅Ρ… ΠΏΠΎΡ€ Π±Ρ‹Π»ΠΎ ΠΏΡ€ΠΎΠ²Π΅Π΄Π΅Π½ΠΎ мноТСство исслСдований Π² ΡΡ‚ΠΎΠΌ Π½Π°ΠΏΡ€Π°Π²Π»Π΅Π½ΠΈΠΈ.

Π’ Ρ€Π°Π±ΠΎΡ‚Π΅ ΠΏΠΎΠ΄Ρ€ΠΎΠ±Π½ΠΎ описываСтся домСнная структура, Ρ„ΡƒΠ½ΠΊΡ†ΠΈΠΈ ΠΈ Π±ΠΈΠΎΡ…имичСскиС свойства Π±Π΅Π»ΠΊΠΎΠ² сСмСйства ядСрных Ρ€Π΅Ρ†Π΅ΠΏΡ‚ΠΎΡ€ΠΎΠ² (Π½Π° ΠΏΡ€ΠΈΠΌΠ΅Ρ€Π΅ 17Π -эстрадиола) ΠΈ Ρ€Π°ΡΡΠΌΠ°Ρ‚Ρ€ΠΈΠ²Π°ΡŽΡ‚ΡΡ особСнности l, 25(OH)2D3 ΠΊΠ°ΠΊ прСдставитСля этого ΠΆΠ΅ сСмСйства. ΠžΠΏΠΈΡΡ‹Π²Π°ΡŽΡ‚ΡΡ Ρ‚Π°ΠΊΠΆΠ΅ Ρ„Π°ΠΊΡ‚ΠΎΡ€ роста ΠΊΠ΅Ρ€Π°Ρ‚ΠΈΠ½ΠΎΡ†ΠΈΡ‚ΠΎΠ² ΠΈ ΠΌΠΈΡ‚ΠΎΠ³Π΅Π½-Π°ΠΊΡ‚ΠΈΠ²ΠΈΡ€ΡƒΠ΅ΠΌΡ‹Π΅ ΠΏΡ€ΠΎΡ‚Π΅ΠΈΠ½-ΠΊΠΈΠ½Π°Π·Ρ‹, ΠΏΠΎΡΠΊΠΎΠ»ΡŒΠΊΡƒ ΠΎΠ½ΠΈ ΡΠ²Π»ΡΡŽΡ‚ΡΡ основными мишСнями дСйствия 1,25(OH)2D3h 17(3-эстрадиола, исслСдуСмого Π² Π΄Π°Π½Π½ΠΎΠΉ Ρ€Π°Π±ΠΎΡ‚Π΅.

ЦСль Π΄Π°Π½Π½ΠΎΠΉ Ρ€Π°Π±ΠΎΡ‚Ρ‹ Π·Π°ΠΊΠ»ΡŽΡ‡Π°Π»Π°ΡΡŒ Π² Ρ‚ΠΎΠΌ, Ρ‡Ρ‚ΠΎΠ±Ρ‹ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Ρ‚ΡŒ дСйствиС l, 25(OH)2D3 ΠΈ 17(3-эстрадиола Π½Π° ΠΊΠ»Π΅Ρ‚ΠΊΠΈ Π»ΠΈΠ½ΠΈΠΈ Ρ€Π°ΠΊΠ° Π³Ρ€ΡƒΠ΄ΠΈ ΠΈ Ρ€Π°ΠΊΠ° простаты, ΠΈ Π²Ρ‹ΡΠ²ΠΈΡ‚ΡŒ ΠΈΡ… ΡƒΡ‡Π°ΡΡ‚ΠΈΠ΅ Π² Ρ€Π΅Π³ΡƒΠ»ΡΡ†ΠΈΠΈ Π³Π΅Π½Π° Ρ„Π°ΠΊΡ‚ΠΎΡ€Π° роста ΠΊΠ΅Ρ€Π°Ρ‚ΠΈΠ½ΠΎΡ†ΠΈΡ‚ΠΎΠ² (kg/), Π° Ρ‚Π°ΠΊΠΆΠ΅ ΠΈΡ… Π²Π»ΠΈΡΠ½ΠΈΠ΅ Π½Π° Π½Π΅ΠΊΠΎΡ‚ΠΎΡ€Ρ‹Π΅ ΠΊΠΎΠΌΠΏΠΎΠ½Π΅Π½Ρ‚Ρ‹ МАР-ΠΊΠΈΠ½Π°Π·Π½ΠΎΠ³ΠΎ ΠΏΡƒΡ‚ΠΈ.

Π’ Ρ€Π°Π±ΠΎΡ‚Π΅ Π±Ρ‹Π»ΠΈ поставлСны ΡΠ»Π΅Π΄ΡƒΡŽΡ‰ΠΈΠ΅ Π·Π°Π΄Π°Ρ‡ΠΈ:

1. Π’Ρ‹ΡΠ²ΠΈΡ‚ΡŒ ΠΏΡ€ΠΈ ΠΏΠΎΠΌΠΎΡ‰ΠΈ Ρ€Π°Π·Π»ΠΈΡ‡Π½Ρ‹Ρ… молСкулярно-биологичСских ΠΌΠ΅Ρ‚ΠΎΠ΄ΠΈΠΊ влияниС 1,25-дигидроксивитамина D3 ΠΈ 17(3-эстрадиола Π½Π° Ρ€Π΅Π³ΡƒΠ»ΡΡ†ΠΈΡŽ Π³Π΅Π½Π° Ρ„Π°ΠΊΡ‚ΠΎΡ€Π° роста ΠΊΠ΅Ρ€Π°Ρ‚ΠΈΠ½ΠΎΡ†ΠΈΡ‚ΠΎΠ² (kgf), Π° Ρ‚Π°ΠΊΠΆΠ΅ ΠΎΠΏΡ€Π΅Π΄Π΅Π»ΠΈΡ‚ΡŒ ΡΠΊΡΠΏΡ€Π΅ΡΡΠΈΡŽ Ρ€Π΅Ρ†Π΅ΠΏΡ‚ΠΎΡ€Π° Π²ΠΈΡ‚Π°ΠΌΠΈΠ½Π° D Π² ΠΊΠ»Π΅Ρ‚ΠΊΠ°Ρ… Ρ€Π°ΠΊΠ° ΠΌΠΎΠ»ΠΎΡ‡Π½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ‹ (Π»ΠΈΠ½ΠΈΠΈ MCF7).

2. Найти ΠΏΠΎΡ‚Π΅Π½Ρ†ΠΈΠ°Π»ΡŒΠ½Ρ‹Π΅ рСгуляторныС элСмСнты (HRE) Π² 5'-Ρ„Π»Π°Π½ΠΊΠΈΡ€ΡƒΡŽΡ‰Π΅ΠΉ области Π³Π΅Π½Π° kgf с ΠΏΠΎΠΌΠΎΡ‰ΡŒΡŽ ΠΊΠΎΠΌΠΏΡŒΡŽΡ‚Π΅Ρ€Π½Ρ‹Ρ… ΠΏΡ€ΠΎΠ³Ρ€Π°ΠΌΠΌ ΠΈ Π±Π°Π· Π΄Π°Π½Π½Ρ‹Ρ….

3. Π˜Π·ΡƒΡ‡ΠΈΡ‚ΡŒ влияниС l, 25(OH)2D3 ΠΈ 17Π -эстрадиола Π½Π° ΡƒΡ€ΠΎΠ²Π½ΠΈ ΠΏΡ€ΠΎΠ»ΠΈΡ„Π΅Ρ€Π°Ρ†ΠΈΠΈ Π² ΠΊΠ»Π΅Ρ‚ΠΊΠ°Ρ… Π»ΠΈΠ½ΠΈΠΉ Ρ€Π°ΠΊΠ° Π³Ρ€ΡƒΠ΄ΠΈ (линия MCF7) ΠΈ Ρ€Π°ΠΊΠ° простаты (линия LNCaP).

4. ΠžΠΏΡ€Π΅Π΄Π΅Π»ΠΈΡ‚ΡŒ влияниС l, 25(OH)2D3 ΠΈ 17(3-эстрадиола Π½Π° Π°ΠΊΡ‚ΠΈΠ²Π°Ρ†ΠΈΡŽ ΠΈ ΠΈΠ½Π³ΠΈΠ±ΠΈΡ€ΠΎΠ²Π°Π½ΠΈΠ΅ Π½Π΅ΠΊΠΎΡ‚ΠΎΡ€Ρ‹Ρ… ΠΊΠΎΠΌΠΏΠΎΠ½Π΅Π½Ρ‚ΠΎΠ² МАР-ΠΊΠΈΠ½Π°Π·Π½ΠΎΠ³ΠΎ каскада, ΠΏΠ΅Ρ€Π΅Π΄Π°ΡŽΡ‰Π΅Π³ΠΎ сигнал ΠΎΡ‚ ΠΏΠΎΠ²Π΅Ρ€Ρ…ности ΠΊΠ»Π΅Ρ‚ΠΊΠΈ Π²Π½ΡƒΡ‚Ρ€ΠΈΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½Ρ‹ΠΌ структурам.

Π²Ρ‹Π²ΠΎΠ΄Ρ‹.

1. ΠŸΡ€ΠΎΠ΄ΡƒΠΊΡ†ΠΈΡ РНК ΠΈ Π±Π΅Π»ΠΊΠ° KGF Π³Π΅Π½ΠΎΠΌ Ρ„Π°ΠΊΡ‚ΠΎΡ€Π° роста ΠΊΠ΅Ρ€Π°Ρ‚ΠΈΠ½ΠΎΡ†ΠΈΡ‚ΠΎΠ² kgf возрастаСт ΠΏΠΎΠ΄ дСйствиСм 1,25-дигидроксивитамина D3 (l, 25(OH)2D3) ΠΈ 17(3-эстрадиола.

2. Π’ 5″ -Ρ„Π»Π°Π½ΠΊΠΈΡ€ΡƒΡŽΡ‰Π΅ΠΉ области Π³Π΅Π½Π° kgf Π½Π°ΠΉΠ΄Π΅Π½Ρ‹ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°Ρ‚Π΅Π»ΡŒΠ½ΠΎΡΡ‚ΠΈ, ΠΏΠΎΡ‚Π΅Π½Ρ†ΠΈΠ°Π»ΡŒΠ½ΠΎ отвСтствСнныС Π·Π° Ρ€Π΅Π³ΡƒΠ»ΡΡ†ΠΈΡŽ Π³Π΅Π½Π° kgf стСроидными Π³ΠΎΡ€ΠΌΠΎΠ½Π°ΠΌΠΈ ΠΈ Π²ΠΈΡ‚Π°ΠΌΠΈΠ½ΠΎΠΌ D3.

3. Π”Π»ΠΈΡ‚Π΅Π»ΡŒΠ½ΠΎΠ΅ (Π² Ρ‚Π΅Ρ‡Π΅Π½ΠΈΠ΅ 1−6 сут) дСйствиС l, 25(OH)2D3 ΠΈ 17)3-эстрадиола ΠΏΠΎ-Ρ€Π°Π·Π½ΠΎΠΌΡƒ мСняСт ΠΏΡ€ΠΎΠ»ΠΈΡ„Π΅Ρ€Π°Ρ†ΠΈΡŽ ΠΊΠ»Π΅Ρ‚ΠΎΠΊ MCF7 ΠΈ LNCaP. 17Π -эстрадиол Π°ΠΊΡ‚ΠΈΠ²ΠΈΡ€ΡƒΠ΅Ρ‚, a l, 25(OH)2D3 ΠΈΠ½Π³ΠΈΠ±ΠΈΡ€ΡƒΠ΅Ρ‚ ΠΏΡ€ΠΎΠ»ΠΈΡ„Π΅Ρ€Π°Ρ†ΠΈΡŽ ΠΊΠ»Π΅Ρ‚ΠΎΠΊ MCF7 ΠΈ LNCaP.

4. Быстрым ΠΎΡ‚Π²Π΅Ρ‚ΠΎΠΌ (Π² Ρ‚Π΅Ρ‡Π΅Π½ΠΈΠ΅ ΠΌΠΈΠ½ΡƒΡ‚) Π½Π° ΡΡ‚ΠΈΠΌΡƒΠ»ΡΡ†ΠΈΡŽ l, 25(OH)2D3 являСтся активация элСмСнтов МАР-ΠΊΠΈΠ½Π°Π·Π½ΠΎΠ³ΠΎ каскада Π² ΠΊΠ»Π΅Ρ‚ΠΊΠ°Ρ… ΠΎΠ±Π΅ΠΈΡ… исслСдованных Π»ΠΈΠ½ΠΈΠΉ. Π”Π»ΠΈΡ‚Π΅Π»ΡŒΠ½Π°Ρ ΠΏΡ€Π΅Π΄Π²Π°Ρ€ΠΈΡ‚Π΅Π»ΡŒΠ½Π°Ρ ΠΎΠ±Ρ€Π°Π±ΠΎΡ‚ΠΊΠ° (Π² Ρ‚Π΅Ρ‡Π΅Π½ΠΈΠ΅ Π½Π΅ΡΠΊΠΎΠ»ΡŒΠΊΠΈΡ… суток) 1,25-дигидроксивитамином D3 подавляСт быстрый ΠΎΡ‚Π²Π΅Ρ‚ ΠΊΠ»Π΅Ρ‚ΠΎΠΊ — фосфорилированиС МАР-ΠΊΠΈΠ½Π°Π· ΠΏΡ€ΠΈ дСйствии 17{3-эстрадиола.

ΠŸΠΎΠΊΠ°Π·Π°Ρ‚ΡŒ вСсь тСкст

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