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

S Muttukrishna, Paul Alfred Francois Fowler, L George, N P Groome, G P Knight

Research output: Contribution to journalArticle

164 Citations (Scopus)

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 bye 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) activin 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 = 0.02), with highest levels around midcycle (similar to 220 pg/mL) and the late luteal/early follicular phase (similar to 310 pg/mL) and nadirs in both midfollicular (similar to 125 pg/mL) and midluteal (similar to 120 pg/mL) phases. Between the mid- to late luteal phase, the activin A level increased progressively (similar to 2.5-fold;P < 0.05), whereas inhibin A, estradiol, and progesterone all decreased progressively (similar to 10-fold; P < 0.001). During pregnancy, serum activin A levels 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 similar to 2 ng/mL between weeks 8-24, but increased thereafter to reach 25.5 +/- 6 ng/mL by week 38, a value similar to 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 < 0.001), estradiol (r = 0.55; P < 0.001), 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 any, free activin (molecular mass, 25 kDa) 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.

Original languageEnglish
Pages (from-to)3328-3334
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume81
Issue number9
Publication statusPublished - Sep 1996

Keywords

  • human follicular-fluid
  • human-placenta
  • binding-proteins
  • dimeric inhibin
  • beta-subunit
  • follistatin
  • identification
  • secretion
  • cells

Cite this

Changes in peripheral serum levels of total activin A during the human menstrual cycle and pregnancy. / Muttukrishna, S ; Fowler, Paul Alfred Francois; George, L ; Groome, N P ; Knight, G P.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 81, No. 9, 09.1996, p. 3328-3334.

Research output: Contribution to journalArticle

@article{26b75d04b0cd45878f286ecd662e0e0b,
title = "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 bye 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) activin 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 = 0.02), with highest levels around midcycle (similar to 220 pg/mL) and the late luteal/early follicular phase (similar to 310 pg/mL) and nadirs in both midfollicular (similar to 125 pg/mL) and midluteal (similar to 120 pg/mL) phases. Between the mid- to late luteal phase, the activin A level increased progressively (similar to 2.5-fold;P < 0.05), whereas inhibin A, estradiol, and progesterone all decreased progressively (similar to 10-fold; P < 0.001). During pregnancy, serum activin A levels 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 similar to 2 ng/mL between weeks 8-24, but increased thereafter to reach 25.5 +/- 6 ng/mL by week 38, a value similar to 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 < 0.001), estradiol (r = 0.55; P < 0.001), 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 any, free activin (molecular mass, 25 kDa) 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.",
keywords = "human follicular-fluid, human-placenta, binding-proteins, dimeric inhibin, beta-subunit, follistatin, identification, secretion, cells",
author = "S Muttukrishna and Fowler, {Paul Alfred Francois} and L George and Groome, {N P} and Knight, {G P}",
year = "1996",
month = "9",
language = "English",
volume = "81",
pages = "3328--3334",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "9",

}

TY - JOUR

T1 - Changes in peripheral serum levels of total activin A during the human menstrual cycle and pregnancy

AU - Muttukrishna, S

AU - Fowler, Paul Alfred Francois

AU - George, L

AU - Groome, N P

AU - Knight, G P

PY - 1996/9

Y1 - 1996/9

N2 - 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 bye 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) activin 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 = 0.02), with highest levels around midcycle (similar to 220 pg/mL) and the late luteal/early follicular phase (similar to 310 pg/mL) and nadirs in both midfollicular (similar to 125 pg/mL) and midluteal (similar to 120 pg/mL) phases. Between the mid- to late luteal phase, the activin A level increased progressively (similar to 2.5-fold;P < 0.05), whereas inhibin A, estradiol, and progesterone all decreased progressively (similar to 10-fold; P < 0.001). During pregnancy, serum activin A levels 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 similar to 2 ng/mL between weeks 8-24, but increased thereafter to reach 25.5 +/- 6 ng/mL by week 38, a value similar to 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 < 0.001), estradiol (r = 0.55; P < 0.001), 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 any, free activin (molecular mass, 25 kDa) 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.

AB - 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 bye 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) activin 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 = 0.02), with highest levels around midcycle (similar to 220 pg/mL) and the late luteal/early follicular phase (similar to 310 pg/mL) and nadirs in both midfollicular (similar to 125 pg/mL) and midluteal (similar to 120 pg/mL) phases. Between the mid- to late luteal phase, the activin A level increased progressively (similar to 2.5-fold;P < 0.05), whereas inhibin A, estradiol, and progesterone all decreased progressively (similar to 10-fold; P < 0.001). During pregnancy, serum activin A levels 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 similar to 2 ng/mL between weeks 8-24, but increased thereafter to reach 25.5 +/- 6 ng/mL by week 38, a value similar to 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 < 0.001), estradiol (r = 0.55; P < 0.001), 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 any, free activin (molecular mass, 25 kDa) 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.

KW - human follicular-fluid

KW - human-placenta

KW - binding-proteins

KW - dimeric inhibin

KW - beta-subunit

KW - follistatin

KW - identification

KW - secretion

KW - cells

M3 - Article

VL - 81

SP - 3328

EP - 3334

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 9

ER -