Changes in peripheral serum levels of total activin A during the human menstrual cycle and pregnancy.

Abstract

The main objective of this study was to determine whether activin A concentrations in peripheral blood fluctuate during the normal human menstrual cycle and pregnancy. Blood samples were collected longitudinally from five regularly cycling volunteers (22-30 yr) throughout a spontaneous menstrual cycle and cross-sectionally from normal pregnant women attending the antenatal clinic (8-38 weeks gestation; 3-20 subjects/time point). Total (i.e. bound plus free) ac-tivin A concentrations were measured using a recently developed two-site enzyme immunoassay that employs an analyte denaturation/ oxidation step to eliminate interference due to endogenous activin-binding proteins. During the menstrual cycle, mean serum activin A levels varied in a biphasic manner (by ANOVA, P = 0.021, with highest levels around midcycle (-220 pg/mL) and the late luteal/early follicular phase (-310 pg/mL) and nadirs in both midfollicular (-125 pg/mL) and midluteal (-120 pg/mL) phases. Between the mid-to late luteal phase, the activin A level increased progressively (-2.5fold; P < 0.051, whereas inhibin A, estradiol, and progesterone all decreased progressively (-lo-fold; P < 0.001). During pregnancy, serum activin Alevels were much higher than those in nonpregnant subjects, with a value of 2.12 + 0.31 ng/mL recorded in week 8. Levels remained at-2 ng/mL between weeks 8-24, but increased thereafter to reach 25.5 + 6 ng/mL by week 38, a value-100 times greater than that during the normal menstrual cycle. Serum activin A levels during pregnancy were significantly correlated with inhibin A (r = 0.69; P < 0.0011, estradiol (r = 0.55; P < O.OOl), and progesterone (r = 0.74; P < 0.001) values. Gel permeation chromatography indicated that all of the detectable activin A in human follicular fluid, pregnancy serum, and term placental extract eluted with an apparent molecular mass between 70-200 kDa, indicating that little. if anv. free activin (mo-lecular mass, 25 kD& is present in these samples. Although these results support a possible endocrine role for circulating activin A during the human menstrual cycle and pregnancy, the observation that all detectable activin A is associated with binding protein(s) raises questions about its relative bioavailability for action on peripheral target cells. (J Clin Endocrinol Metab 81: 3328-3334, 1996)