다운 증후군과 임신 합병증에서 임신 제 2삼분기 양수내 Activin A, Inhibin A 와 B 의 농도와 이들 비율의 의의 = Midtrimester Amniotic Fluid Levels and Each Ratio of Activn A, Inhibin A and B in Down`s Syndrome and Other Complicated Pregnancies

국문 초록 (Abstract)

목적 : 모성 연령, 임신 주수, 성별에 따른 activin A, inhibin A와 B의 변화와 다운 증후곤과 임신 합병증이 동반된 임신에서 이들 단백질의 농도와 비율의 변화를 조사하고자 하였다.
연구 방법 : 임신 제 2삼분기에 양수천자술을 시행한 71예를 대상으로 하였으며, 임신 예후는 의무기록을 통하여 후향적으로 조사하였다. 다운 증후군 10예를 연구군으로, 정상 염색체 소견을 보인 61예를 비교군으로 하였다. 임신 합병증군은 정상 염색체 소견을 보인 61예 중 15예였으며, 자간전중 (preeclamsia), 임신성 당뇨, 조산, 자궁내 발육지연, 사산 등이 포함되어 있다. 양수내 activin A, inhibin A와 B의 농도는 효소결합면역흡착검사(ELISA)를 통해 측정하였으며, 통계분석을 Mann-Whitney U test와 regression analysis를 시행하였다.
결과 : activin A/inhibin B 비율과 산모 연령사이에 유의한 상관관계 (r=0.277, p=0.011)가 있었으며, inhibin A/inhibin B와 산모 연령사이에도 유의한 상관관계 9r=0.261, p=0.015)가 있었다. inhibin A 농도와 임신주수 사이에 유의한 상관관계 (r=0.474, p<0.001)가 있었다. 양수내 inhibin A와 inhibin B 농도는 다운증후군 군에서 유의하게 낮았으나 (p<0.05), activin A/inhibin B 비율과 inhibin A/inhibin B 비율에서는 유의한 차이를 보이지 않았다. 임신 합병증이 동반된 정상 염색체 군에서 양수내 inhibin A와 B, activin A의 농도와 이들 사이의 비율은 합병증이 동반되지 않은 군과 비교하여 유의한 차이가 없었다.
결론 : 본 연구에서는 다운 증후군 임신시 제 2삼분기 양수내 inhibin a와 B는 유의하게 감소하였으나, activin A와 이들 사이의 비율은 변화하지 않았다. 이러한 사실은 다운 증후군 임신시 양수내 inhibin의 감소와 함계 activin A의 상대적 감소가 동반될 수 있음을 의미한다.

다국어 초록 (Multilingual Abstract)

Objective : To evaluate the amniotic fluid levels and each ratio of activin A, inhin A and B in Down`s syndrome and other complicated pregnancies. Methods : This study was performed in 71 women who had undergone a midtrimester amniocentesis with the clinical indications and whose pregnancy outcome was retropsectively determined. Ten Down`s syndrome, 15 complicated pregnancies including, preeclamsia, gestational diabetesis mellitus, preterm labor, intrauterine growth restriction (IUGR), and 46 noncomplicated pregnancies with normal chromosome were included in this study. Amniotic fluid activin A, inhibin A and B were measure using enzyme linked immunosorbent assays (ELISA). Statistical analysis was performed with Mann-Whitney U test and regression analysis. Results : There were significant positive correlation (r=0.277, p=0.011) between the ratio activin A/inhibin B level and maternal age and significant positive correlation (r=0.261, p=0.015) between maternal age and the ratio inhibin A/inhibin B level. There were also significant positive correlation (r=0.202, p=0.045) between gestational weeks and inhibin A levels and significant positive correlation (r=0.474, p<0.001_ between gestational weeks and inhibin B levels. Amniotic fluid inhibin A and inhibin B levels were significantly (p<0.05) decreased in Down`s syndrome compared with the normal chromosomal groups but there was no difference in the ratio activin A/inhibin A and in the ratio activin A/inhibin B between these groups. The amniotic fluid levels of activin A, inhibins (A and B), each ratio of complicated pregnancies groups with normal chromosome was not significantly different from those of uncomplicated pregnancies with normal chromosome. Conclusion : This study revealed that amniotic inhibin levels were significantly decreased in Down`s sundrome. But, activin A and each ratio were unchanged. The results suggest that activin A may by relatively decreased in each case of Down`s syndrome.

참고문헌 (Reference)

1 "α fetoprotein, free β chorionic gonadotropin, and dimeric inhibin A produce the best results in a three-analyte. multiple marker screening test for Down syndrome" 177 : 987-991, 1997

2 "Steroid hormones modulate the release of immunoreactive gonadotropin-releasing hormone from cultured human placent cells" 70 : 1173-1178, 1990

3 "Serum screening for Down's syndrome between 8 and 14 weeks of pregnancy. International Prenatal Screening Research Group" 103 : 407-412, 1996

4 "Serum immunoactive inhibin levels in early pregnancy after in vitro fertilization and embryo transfer" 59 : 1081-1089, 1993

5 "Second trimester maternal serum immunoreactive inhibin as a marker for fetal Down's syndrome" 12 : 801-806, 1992

6 "Prenatal screening for Down's syndrome using inhibin A as serum marker" 16 : 143-153, 1996

7 "Peptide signalling in human placenta and membranes: autocrine, paracrine, and endocrine mechanisms" 17 : 156-186, 1996

8 "Measurement of inhibin and activin in early human pregnancy:demonstration of fetoplacental origin and role in prediction of early- pregnancy outcome" 57 : 1490-1494, 1997

9 "Measurement of inhibin A and activin A in pregnancy- possible diagnostic applications" 180 : 117-121, 2001

10 "Maternal serum inhibin levels in second- trimester Down's syndrome" 14 : 387-390, 1994

11 "Maternal serum inhibin A can be predict pre-eclamsia" 105 : 1101-1103, 1998

12 "Maternal serum inhibin A and free beta hCG concentrations in trisomy 21 pregnancies at 10 to 14 weeks of gestation" 104 : 367-371, 1997

13 "Local production and action of follistatin in human placenta" 78 : 205-210, 1994

14 "Local extragonadal roles of activins" 3 : 218-223, 1992

15 "Inhibins, activins and follistatin: gonadal proteins modulating the secretion of follicle-stimulating hormone" 9 : 267-293, 1988

16 "Inhibin, a new circulating marker in hydatiform mole" 298 : 1684-1686, 1989

17 "Inhibin suppresses human chorionic gonadotropin secretion in term, but not first trimester, placenta" 71 : 1294-1298, 1990

18 "Inhibin subunit in human placenta:localization and messenger ribonucleic acid levels during pregnancy" 165 : 750-758, 1991

19 "Inhibin production and secretion in human placental cells cultured in vitro" 79 : 705 -712, 1992

20 "Inhibin and activin:roles in clinical practice" 103 : 945-956, 1996

21 "Inhibin and activin regulate 3H Thymidine uptake by rat thymocytes and 3T3 cells in vitro" 120 : 133-138, 1989

22 "Immunohistochemical localization of inhibin/activin subunits in human placenta" 80 : 410-414, 1992

23 "Hypertension in pregnancy:changes in activin A maternal serum concentration" 16 : 447-454, 1995

24 "Gonadotropin releasing-hormone, inhibin and activin in human placenta: evidence for a common cellular localization" 77 : 1184-1188, 1992

25 "Evaluation of maternal serum dimeric inhibin A as a first trimester marker of Down's syndrome" 15 : 359 -362, 1995

26 "Dimeric inhibin in amniotic fluid, maternal serum and fetal serum in human pregnancy" 82 : 218-222, 1997

27 "Dimeric inhibin A as a marker for Down's syndrome in early pregnancy" 334 : 1321-1326, 1996

28 "Chemical and biological characterization of the inhibin family of protein hormones" 44 : 1-34, 1988

29 "Amniotic fluid levels of dimeric inhibins, pro-αC inhibin, activin A and follistatin in Down's syndrome" 50 : 669-673, 1999

30 "Amniotic fluid concentrations of dimeric inhibins, activin A and follistatin in pregnancy" 140 : 420-424, 1999

31 "Advances in a the physiology of inhibin and inhibin related peptides" 29 (29): 77-114, 1988

32 "Acute stimulation of human chorionic gonadotropin secretion by recombinant human activin A in first trimester human trophoblast" 133 : 297-303, 1993

33 "Activin A and inhibin A as possible endocrine markers for pre-eclamsia" 349 : 1285-1288, 1997

34 "Abnormal concentration of maternal serum activin A in gestational diseases" 80 : 558-561, 1995

35 "A longitudinal study of maternal serum inhibin-A pro-alphaC and follistatin during pregnancy" 13 : 3530-3536, 1998