RSS-Feed abonnieren
DOI: 10.1055/s-2004-831898
Role of Inhibin in Normal and High-Risk Pregnancy
Publikationsverlauf
Publikationsdatum:
20. August 2004 (online)
Inhibins are glycoprotein hormones of which there are two molecular forms, inhibin A and inhibin B. Classically, inhibin is known to have a negative feedback effect on pituitary follicle-stimulating hormone secretion. The fetoplacental unit produces inhibin throughout pregnancy. Inhibin A is the predominant molecular form of inhibin in maternal circulation from 4 weeks of gestation. Although the precise biological function of inhibin A in pregnancy is unclear, it is evident from recent studies that inhibin A could be a better marker of placental function than human chorionic gonadotropin because of its shorter half-life. The possible clinical applications for the measurement of inhibin A in early pregnancy could be in predicting miscarriage, Down's syndrome, preeclampsia, and fetal growth restriction in the first and/or second trimester before the onset of the clinical symptoms. The source of inhibins, factors controlling inhibin production, the possible functions of inhibin, and the use of inhibin measurement in normal and high-risk pregnancy are reviewed.
KEYWORDS
Inhibin - pregnancy - preeclampsia - placenta - miscarriage
REFERENCES
- 1 Ying S-Y. Inhibins, activins and follistatins: gonadal proteins modulating the secretion of follicle stimulating hormone. Endocr Rev. 1988; 9 267-293
- 2 Mather J P, Moore A, Li R H. Activins, inhibins, and follistatins: further thoughts on a growing family of regulators. Proc Soc Exp Biol Med. 1997; 215 209-222
- 3 Groome N P, Illingworth P J, O'Brien M et al.. Detection of dimeric inhibin throughout the human menstrual cycle by two-site enzyme immunoassay. Clin Endocrinol (Oxf). 1994; 40 717-723
- 4 Groome N P, Illingworth P J, O'Brien M et al.. Measurement of dimeric inhibin B throughout the human menstrual cycle. J Clin Endocrinol Metab. 1996; 81 1321-1325
- 5 Muttukrishna S, Child T J, Groome N P, Ledger W L. Source of circulating levels of inhibin A, pro alpha C-containing inhibins and activin A in early pregnancy. Hum Reprod. 1997; 12 1089-1093
- 6 Lockwood G M, Ledger W L, Barlow D H, Groome N P, Muttukrishna S. Measurement of inhibin and activin in early human pregnancy: demonstration of feto-placental origin and role in prediction of early pregnancy outcome. Biol Reprod. 1997; 57 1490-1494
- 7 Riley S C, Neville C W, Chard T, Groome N P, Wallace E. Inhibin in extra-embryonic coelomic and amniotic fluids and maternal serum in early pregnancy. Hum Reprod. 1996; 11 2772-2776
- 8 Wallace E M, Riley S C, Crossley J A et al.. Dimeric inhibins in amniotic fluid, maternal serum and fetal serum in human pregnancy. J Clin Endocrinol Metab. 1997; 82 218-222
- 9 McLachlan R I, Healy D L, Robertson D M, Burger H G, de Kretser D M. Circulating immunoreactive inhibin in the luteal phase and early gestation in women undergoing ovulation induction. Fertil Steril. 1987; 48 1001-1005
- 10 Abe Y, Hasegawa Y, Miyamoto K et al.. High concentrations of plasma immunoreactive inhibin during normal pregnancy in women. J Clin Endocrinol Metab. 1990; 71 133-137
- 11 Tabie T, Ochiai K, Terashima Y, Takanashi N. Serum levels of inhibin in maternal and umbilical blood during pregnancy. Am J Obstet Gynecol. 1991; 164 896-900
- 12 Yohkaichiya T, Polson D, O'Connor A et al.. Concentrations of immunoreactive inhibin in serum during human pregnancy: evidence for an ovarian contribution. Reprod Fertil Dev. 1991; 3 671-678
- 13 Baird D T, Smith K B. Inhibin and related peptides in the regulation of reproduction. Oxf Rev Reprod Biol. 1993; 15 191-232
- 14 McLachlan R I, Robertson D M, Burger H G, de Kretser D M. The radioimmunoassay of bovine and human follicular fluid and serum inhibin. Mol Cell Endocrinol. 1986; 46 175-185
- 15 Muttukrishna S, George L, Fowler P A, Groome N P, Knight P G. Measurement of serum concentrations of inhibin A (α-βA dimer) during human pregnancy. Clin Endocrinol (Oxf). 1995; 42 391-397
- 16 Illingworth P J, Groome N P, Duncan W C et al.. Measurement of circulating inhibin forms during the establishment of pregnancy. J Clin Endocrinol Metab. 1996; 81 1471-1475
- 17 Fowler P A, Evans L W, Groome N P, Templeton A, Knight P G. A longitudinal study of maternal serum inhibin-A, inhibin-B, activin-A, activin-AB, pro-alphaC and follistatin during pregnancy. Hum Reprod. 1998; 13 3530-3536
- 18 Petraglia F, Garuti G C, Calza L et al.. Inhibin subunits in human placenta: localization and messenger ribonucleic acid levels during pregnancy. Am J Obstet Gynecol. 1991; 165 750-758
- 19 Petraglia F, Gallinelli A, Grande A et al.. Local production and action of follistatin in human placenta. J Clin Endocrinol Metab. 1994; 78 205-210
- 20 Petraglia F, Calza L, Garuti G C et al.. Presence and synthesis of inhibin subunits in human decidua. J Clin Endocrinol Metab. 1990; 71 487-492
- 21 Petraglia F, Lim A TW, Rivier J, Vale W. Localisation, secretion and action of inhibin in human placenta. Science. 1987; 237 187-189
- 22 Minami S, Yamoto M, Nakano R. Immunohistochemical localization of inhibin/activin subunits in human placenta. Obstet Gynecol. 1992; 80 410-414
- 23 McCluggage W G, Ashe P, McBride H, Maxwell P, Sloan J M. Localization of the cellular expression of inhibin in trophoblastic tissue. Histopathology. 1998; 32 252-256
- 24 Yamoto M, Minami S, Nakano R. Immunohistochemical localization of inhibin subunits in human corpora lutea during menstrual cycle and pregnancy. J Clin Endocrinol Metab. 1991; 73 470-477
- 25 Birdsall M, Ledger W L, Groome N P, Abdalla H, Muttukrishna S. Inhibin A and activin A in the first trimester of human pregnancy. J Clin Endocrinol Metab. 1997; 82 1557-1560
- 26 Riley S C, Leask R, Balfour C, Brennand J E, Groome N. Production of inhibin forms by the fetal membranes, decidua, placenta and fetus at parturition. Hum Reprod. 2000; 15 578-583
- 27 Riley S C, Balfour C, Wathen N C et al.. Follistatin and activin A in extra embryonic coelomic and amniotic fluids and maternal serum in early pregnancy. Hum Reprod. 1998; 13 2624-2628
- 28 Luisi S, Battaglia C, Florio P et al.. Activin A and inhibin B in extra -embryonic coelomic and amniotic fluids and maternal serum in early pregnancy. Placenta. 1998; 19 435-438
- 29 Muttukrishna S, Chamberlain P, Evans L W, Asselin J, Groome N P, Ledger W L. Amniotic fluid concentrations of dimeric inhibins, activin A and follistatin in pregnancy. Eur J Endocrinol. 1999; 140 420-424
- 30 Muttukrishna S, Jauniaux E, Pahal G, Groome N P, Rodeck C H. In vivo distribution of inhibin A, activin A and follistatin in early pregnancy. Presented at the European Congress in Obstetrics and Gynaecology Ceska Gynekol; 2002 2(suppl): 76
- 31 Debieve F, Beerlandt S, Hubinont C, Thomas K. Gonadotropins, prolactin, inhibin A, inhibin B and activin A in human fetal serum from midpregnancy and term pregnancy. J Clin Endocrinol Metab. 2000; 85 270-274
- 32 Florio P, Severi F M, Luisi S et al.. Abnormal umbilical artery Doppler waveforms and cord blood inhibin A and inhibin B levels. Biol Neonate. 2003; 84 281-286
- 33 Jenkin G, McFarlane J R, de Kretser D M. Implication of inhibin and related proteins in fetal development. Reprod Fertil Dev. 1995; 7 323-331
- 34 Qu J, Thomas K. Regulation of inhibin secretion in human placental cell culture by epidermal growth factor, transforming growth factors and activin. J Clin Endocrinol Metab. 1993; 77 925-931
- 35 Qu J, Thomas K. Prostaglandins stimulate the secretion of inhibin from human placental cells. J Clin Endocrinol Metab. 1993; 77 556-564
- 36 Keelan J, Song Y, France J T. Comparative regulation of inhibin, activin and human chorionic gonadotrophin production by placental trophoblast cells in culture. Placenta. 1994; 15 803-818
- 37 Bandivdekar A H, Varadkar A M, Sheth A R. Endocrine control of inhibin biosynthesis by human placenta. Biol Res Pregnancy Perinatol. 1985; 6 128-132
- 38 Mohan A, Asselin J, Sargent I L, Groome N P, Muttukrishna S. Effect of cytokines and growth factors on the secretion of inhibin A, activin A and follistatin by term placental villous trophoblasts in culture. Eur J Endocrinol. 2001; 145 505-511
- 39 Manuelpillai U, Schneider-Kolsky M, Thirunavukarasu P, Dole A, Waldron K, Wallace E M. Effect of hypoxia on placental activin A, inhibin A and follistatin synthesis. Placenta. 2003; 24 77-83
- 40 Blumenstein M, Mitchell M D, Groome N P, Keelan J A. Hypoxia inhibits activin A production by term villous trophoblast in vitro. Placenta. 2002; 23 735-741
- 41 Petraglia F, Vaughan J, Vale W. Inhibin and activin modulate the release of gonadotropin-releasing hormone, human chorionic gonadotropin, and progesterone from cultured human placental cells. Proc Natl Acad Sci USA. 1989; 86 5114-5117
- 42 Mersol-Barg M S, Miller K F, Choi C M, Lee A C, Kim M I. Inhibin suppresses chorionic gonadotrophin secretion in term but not first trimester placenta. J Clin Endocrinol Metab. 1990; 71 1294-1298
- 43 Steele G L, Currie W D, Yuen B H, Jia X C, Perlas E, Leung P CK. Acute stimulation of chorionic gonadotrophin secretion by recombinant human activin A in first trimester human trophoblast. Endocrinology. 1993; 133 297-303
- 44 Leung P H, Salamonsen L-A, Findlay J K. Immunolocalization of inhibin and activin subunits in human endometrium across the menstrual cycle. Hum Reprod. 1998; 13 3469-3477
- 45 Ethier J F, Findlay J K. Roles of activin and its signal transduction mechanisms in reproductive tissue. Reproduction. 2001; 121 667-675
- 46 Otani T, Minami S, Yamoto M, Umesaki N. Production of activin A in hyperplasia and adenocarcinoma of the human endometrium. Gynecol Oncol. 2001; 83 31-38
- 47 Jones R L, Salamonsen L A, Critchley H O, Rogers P A, Affandi B, Findlay J K. Inhibin and activin subunits are differentially expressed in endometrial cells and leukocytes during the menstrual cycle, in early pregnancy and in women using progestin-only contraception. Mol Hum Reprod. 2000; 6 1107-1117
- 48 Healy D L, Mamers P, Bangah M, Burger H G. Clinical and pathophysiological aspects of inhibin. Hum Reprod. 1993; 8 138-140
- 49 Yohkaichiya T, Fudaya T, Hoshiai H, Yajima A, de Kretser D M. Inhibin, a new circulating marker in hydatidiform mole. BMJ. 1989; 298 1684-1686
- 50 Minami S, Yamoto M, Nakano R. Immunohistochemical localisation of inhibin-activin subunits in hydatidiform mole and invasive mole. Obstet Gynecol. 1993; 82 414-418
- 51 Kato T, Seki K, Matsui H, Sekiya S. Circulating inhibin forms in patients with hydatidiform mole. Gynecol Obstet Invest. 2002; 54 114-117
- 52 Florio P, Severi F M, Cobellis L et al.. Serum activin A and inhibin A: new clinical markers for hydatidiform mole. Cancer. 2002; 94 2618-2622
- 53 Yohkaichiya T, Polson D W, Hughes E G et al.. Serum immunoreactive inhibin levels in early pregnancy after in vitro fertilisation and embryo transfer. Fertil Steril. 1993; 59 1081-1089
- 54 Seifer D B, Labertmesserlian G M, Canick J A, Frishman G N, Schneyer A L. Serum inhibin levels are lower in ectopic than intrauterine spontaneously conceived pregnancies. Fertil Steril. 1996; 65 667-669
- 55 Lockwood G M, Ledger W L, Barlow D H, Groome N P, Muttukrishna S. Identification of the source of inhibins at the time of conception provides a diagnostic role for them in very early pregnancy. Am J Reprod Immunol. 1998; 40 303-308
- 56 Muttukrishna S, Jauniaux E, Greenwold N et al.. Levels of inhibin A, activin A and follistatin in missed and recurrent miscarriages. Hum Reprod. 2002; 17 3072-3078
- 57 Luisi S, Florio P, D'Antona D et al.. Maternal serum inhibin A levels are a marker of a viable trophoblast in incomplete and complete miscarriage. Eur J Endocrinol. 2003; 148 233-236
- 58 Van Lith J M, Pratt J J, Beekhuis J R, Mantingh A. Second trimester maternal serum immunoreactive inhibin as a marker for fetal Down's syndrome. Prenat Diagn. 1992; 12 801-806
- 59 Spencer K, Wood P J, Antony F W. Elevated levels of maternal serum inhibin immunoreactivity in second trimester pregnancies affected by Down's syndrome. Ann Clin Biochem. 1993; 30 219-220
- 60 Cuckle H S, Holding S, Jones R. Maternal serum inhibin levels in second trimester Down's syndrome pregnancies. Prenat Diagn. 1994; 14 387-390
- 61 Cuckle H S, Holding S, Jones R, Wallace E M, Groome N P. Maternal serum dimeric inhibin A in second trimester Down's syndrome pregnancies. Prenat Diagn. 1995; 15 385-392
- 62 Canick J A, Lambert-Messerlian G M, Palomaki G E et al.. Maternal serum dimeric inhibin is elevated in Down's syndrome pregnancy. Am J Hum Genet. 1994; 55 A37
- 63 Aitken D A, Wallace E M, Crossley J A et al.. Dimeric inhibin A as a marker for Down's syndrome in early pregnancy. N Engl J Med. 1996; 334 1231-1236
- 64 Wallace E M, Healy D L. Inhibins and activins: roles in clinical practice. Br J Obstet Gynaecol. 1996; 103 945-956
- 65 Tul N, Pusenjak S, Osredkar J, Spencer K, Novak-Antolic Z. Predicting complications of pregnancy with first trimester maternal serum free-beta hCG, PAPP A and inhibin A. Prenat Diagn. 2003; 23 990-996
- 66 Benn P A, Fang M, Egan J F, Horne D, Collins R. Incorporation of inhibin A in second trimester screening for Down syndrome. Obstet Gynecol. 2003; 101 451-454
- 67 Dalgliesh G L, Aitken D A, Lyall F, Howatson A G, Connor J M. Placental and maternal serum inhibin-A and activin-A levels in Down's syndrome pregnancies. Placenta. 2001; 22 227-234
- 68 Wallace E M, Crossley J A, Groome N P, Aitken D A. Amniotic fluid inhibin-A in chromosomally normal and Down's syndrome pregnancies. J Endocrinol. 1997; 152 109-112
- 69 Muttukrishna S, Knght G, Groome N P, Redman C WG, Ledger W L. Inhibin A and activin A: new endocrine markers for pre-eclampsia?. Lancet. 1997; 349 1285-1288
- 70 Cuckle H, Sehmi I, Jones R. Maternal serum inhibin A can predict pre-eclampsia. Br J Obstet Gynaecol. 1998; 105 1101-1103
- 71 Lambert-Messerlian G M, Silver H M, Petraglia F et al.. Second-trimester levels of maternal serum human chorionic gonadotropin and inhibin A as predictors of preeclampsia in the third trimester of pregnancy. J Soc Gynecol Investig. 2000; 7 170-174
- 72 Muttukrishna S, North R A, Morris J et al.. Serum inhibin A and activin A are elevated prior to the onset of pre-eclampsia. Hum Reprod. 2000; 15 1640-1645
- 73 Grobman W A, Wang E Y. Serum levels of activin A and inhibin A and the subsequent development of preeclampsia. Obstet Gynecol. 2000; 96 390-394
- 74 Davidson E J, Riley S C, Roberts S A, Shearing C H, Groome N P, Martin C W. Maternal serum activin, inhibin, human chorionic gonadotrophin and alpha-fetoprotein as second trimester predictors of pre-eclampsia. BJOG. 2003; 110 46-52
- 75 Keelan J A, Taylor R, Schellenberg J-C, Groome N P, Mitchell M D, North R A. Serum activin A, inhibin A and follistatin concentrations in pre-eclampsia or small for gestational age pregnancies. Obstet Gynecol. 2002; 99 267-274
- 76 Florio P, Cobellis L, Luisi S et al.. Changes in inhibins and activin secretion in healthy and pathological pregnancies. Mol Cell Endocrinol. 2001; 180 123-130
- 77 Florio P, Ciarmela P, Luisi S et al.. Pre-eclampsia with fetal growth restriction: placental and serum activin A and inhibin A levels. Gynecol Endocrinol. 2002; 16 365-372
- 78 Silver H M, Lambert-Messerlian G M, Reis F M, Diblasio A M, Petraglia F, Canick J A. Mechanism of increased maternal serum total activin A and inhibin A in pre eclampsia. J Soc Gynecol Investig. 2002; 9 308-312
- 79 Bersinger N A, Groome N P, Muttukrishna S. Pregnancy-associated and placental proteins in the placental tissue of normal and pre-eclamptic women at delivery. Eur J Endocrinol. 2002; 147 785-793
- 80 Casagrandi D, Bearfield C, Geary J, Redman C W, Muttukrishna S. Inhibin, activin, follistatin, activin receptors and betaglycan gene expression in the placental tissue of pre eclampsia patients. Mol Hum Reprod. 2003; 9 199-203
- 81 Bobrow C S, Holmes R P, Muttukrishna S et al.. Maternal serum activin A, inhibin A and follistatin in pregnancies with appropriately grown and small for gestational age fetuses classified by umbilical artery Doppler. Am J Obstet Gynecol. 2002; 186 283-287
- 82 D'Antona D, Reis F M, Benedetto C et al.. Increased maternal serum activin A but not follistatin levels in pregnant women with hypertensive disorders. J Endocrinol. 2000; 165 157-162
- 83 Jauniaux E, Watson A L, Hempstock J, Bao Y P, Skepper J N, Burton G J. Onset of maternal arterial blood flow and placental oxidative stress. A possible factor in human early pregnancy failure. Am J Pathol. 2000; 157 2111-2122
- 84 Hustin J, Jauniaux E, Schaaps J P. Histological study of the materno-embryonic interface in spontaneous abortion. Placenta. 1990; 11 477-486
- 85 Jauniaux E, Hempstock J, Greenwold N, Burton G J. Trophoblastic oxidative stress in relation to temporal and regional differences in maternal placental blood flow in normal and abnormal early pregnancies. Am J Pathol. 2003; 162 115-125
- 86 Hung T H, Skepper J N, Burton G J. In vitro ischemia-reperfusion injury in term human placenta as a model for oxidative stress in pathological pregnancies. Am J Pathol. 2001; 159 1031-1043
Shanthi MuttukrishnaB.Sc. Ph.D.
Department of Obstetrics and Gynaecology, Royal Free University College Medical School
86-96 Chenies Mews, London WC1E 6HX, United Kingdom