Activin A, a dimer of the betaA-subunit of inhibin, has been shown to have multiple biological activities and sites of production. Follistatin is a high-affinity binding protein for activin, which neutralizes its activity. This study provides the first data, using a cross-sectional design, on the measurement of both these proteins in the maternal circulation of a large cohort of women (6-39 weeks of gestation, n = 2-20 women/time point) during normal pregnancies, and confirms that similar patterns are seen in nine women studied longitudinally during pregnancy. The concentrations of total activin A were measured using a specific two-site enzyme-linked immunosorbent assay (ELISA), and a new radioimmunoassay for measuring total follistatin in serum utilizing dissociating reagents to eliminate the interference of activin is described. At 38-39 weeks gestation, both activin A and follistatin concentrations rose to a peak (4.59 +/- 0.54 ng/ml and 72.7 +/- 3.31 ng/ml, respectively). The activin A and follistatin concentrations were highly correlated both in the cross-sectional study (P <0.0001) and in individual women in the longitudinal study (P <0.05-0.0001). Concentrations of follistatin showed a greater increase in the second trimester of pregnancy relative to activin A concentrations. The parallel increase in the secretion of these two proteins throughout pregnancy probably reflects feto-placental secretion.

103 to 32-6x 103), they remained far higher than in non-pregnant women. Serum follicle stimulating hormone concentrations remained suppressed.Conclusions-In this small study serum inhibin concentrations higher than those found in the early follicular phase one to two weeks after evacuation of a hydatidiform mole seemed to be specific for persistent trophoblastic disease. Further data are needed to confirm these promising results.

Immunoactive inhibin (ir-inhibin) concentrations in maternal serum during normal human pregnancy have been established in two separate studies employing cross-sectional and longitudinal sampling regimes. Ir-inhibin concentrations rose from the mid-luteal phase (geometric mean + 95% confidence intervals 1.490 (1.086-2.028) U mL-1) to peak at week 11 of gestation (3.77 (3.26-4.35) U mL-1), declined to a plateau from 14 to 25 weeks with means ranging from 1.8 to 2.3 U mL-1, and subsequently rose slowly to a peak of 6.53 U mL-1 at 41 weeks. In the longitudinal study, similar results were obtained and no differences were found in maternal inhibin levels in women carrying male or female fetuses. Paired cord blood and maternal samples showed no significant difference in ir-inhibin concentrations irrespective of the sex of the fetus. However, in all such pregnancies amniotic fluid ir-inhibin levels were 2-3 fold greater than maternal or fetal levels raising the possibility that the amnion may secrete inhibin. In 12 women without functional ovaries in whom a singleton pregnancy was achieved by donation of oocytes and in vitro fertilization, the ir-inhibin levels showed a similar pattern in the first trimester of pregnancy but the concentrations achieved were markedly lower (peak 1.1 U mL-1 at 9 weeks). In five women from the group in whom samples were available late in gestation, three showed greater than normal levels and two had subnormal levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Objective-To define the concentrations ofinhibin in serum and tissue of patients with hydatidiform mole and assess their value as a clinical marker ofthe condition.Design-Prospective study of new patients with hydatidiform mole, comparison of paired observations, and case-control analysis.Setting-A university hospital, two large public hospitals, and a private women's clinic in Japan.Patients-Seven consecutive referred patients seen over four months with newly diagnosed complete hydatidiform mole, including one in whom the mole was accompanied by viable twin fetuses (case excluded from statistical analysis because of unique clinical features). All patients followed up for six months after evacuation of molar tissue.End point-Correlation of serum inhibin concentrations with trophoblastic disease.Measurements and main results-Serum concentrations of inhibin, human chorionic gonadotrophin, and follicle stimulating hormone were compared before and seven to 10 days after evacuation of the mole. Before evacuation the serum inhibin concentrations (median 8*3 U/ml; 95% confidence interval 2-4 to 34.5) were significantly greater than in 21 normal women at the same stage of pregnancy (2.8 U/ml; 2*1 to 3.6), and inhibin in molar tissue was also present in high concentrations (578 U/mI cytosol; 158 to 1162). Seven to 10 days after evacuation inhibin concentrations in serum samples from the same patients declined significantly to values (0 4 U/mI; 0-1 to 1-4) similar to those seen in the follicular phase of normal menstrual cycles. None of the four patients whose serum inhibin concentrations were 0 4 U/mI or less after evacuation developed persistent trophoblastic disease. Though serum human chorionic gonadotrophin concentrations declined after evacuation (6-6x 103 IU/l; 0-8x 103 to 32-6x 103), they remained far higher than in non-pregnant women. Serum follicle stimulating hormone concentrations remained suppressed.Conclusions-In this small study serum inhibin concentrations higher than those found in the early follicular phase one to two weeks after evacuation of a hydatidiform mole seemed to be specific for persistent trophoblastic disease. Further data are needed to confirm these promising results. IntroductionInhibin, a glycoprotein hormone produced by the testis and ovary, has the ability preferentially to suppress the secretion of follicle stimulating hormone by the pituitary. After its initial isolation from bovine follicular fluid' we showed that inhibin was also produced by the placenta2 and that concentrations rose during early pregnancy.3 Other studies using immunocytochemistry have localised inhibin to the cytotrophoblast of the placenta,4 which has been shown to contain messenger ribonucleic acid for the inhibin subunits.5 The production of inhibin by trophoblastic tissue and the availability of specific radioimmunoassays for inhibin prompted us to study the concentrations of inhibin in women with a gestational trophoblastic disease such as hydatidiform mole. This paper reports our results.

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