Plasminogen activator activity during decidualization of human endometrial stromal cells is regulated by plasminogen activator inhibitor 1

F. Schatz, S. Aigner, C. Papp, E. Tóth-Pál, V. Hausknecht, C. J. Lockwood

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Progesterone acts on the estradiol (E2)-conditioned human endometrium to induce decidualization of stromal cells. Consistent with these differential hormone actions in vivo, progestins regulate several end points of decidualization in human endometrial stromal cell monolayers and E2 augments the effects of progestin. This study shows that in vitro decidualization of the stromal cells is accompanied by diminished plasminogen activator (PA) expression. Polyacrylamide gel electrophoretic separation after immunoprecipitation of biosynthetically labeled PAs revealed that medroxyprogesterone acetate (MPA) lowered levels of secreted tissue type PA (tPA) at 67 kilodaltons and urokinase type PA (uPA) at 55 kilodaltons. These levels were reduced further by E2 plus MPA despite a lack of response to E2 alone. Although tPA activity was readily measured by a chromogenic assay, detection of uPA activity required prior activation, indicating that uPA is released as the pro-uPA zymogen. Comparisons of levels of immunogenic PAs, as measured by specific enzyme-linked immunosorbent assays, with the corresponding catalytic activities revealed selective progestational inhibition of PA activity vs. antigen after 3 days of experimental incubation. Thus, 10-7 mol/L MPA produced about a 2-fold greater reduction of levels of PA activity than that of its corresponding antigen. More strikingly, 10-8 mol/L E2 plus 10-7 mol/L MPA virtually eliminated both tPA activity (99% inhibition; P <0.005) and uPA activity (93% inhibition; P <0.005); the reductions in levels of the corresponding antigens were only about 50% of the control levels and did not attain statistical significance. Only after 3-6 days of incubation with E2 plus MPA was statistically significant inhibition achieved for immunogenic levels of both tPA (P <0.05) and uPA (P <0.005). Preferential inhibition of levels of PA activities compared with those of the corresponding PA antigens reflects the action of the potent PA inhibitor PAI-1. Thus, the concentration of PAI-1 in the stromal cell-conditioned medium at the end of 0-3 days exceeded those of tPA and uPA, respectively, by 28- and 12-fold in response to MPA and by 52- and 25-fold in response to E2 plus MPA. Extrapolation of these in vitro results to the events of the luteal phase, whose steroidal milieu is mimicked by E2 plus MPA, indicates that decidual cell-derived PAI-1 is a key regulator of proteolytic degradation of extracellular matrix and fibrinolysis during implantation and menstruation.

Original languageEnglish
Pages (from-to)2504-2510
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume80
Issue number8
Publication statusPublished - 1995

Fingerprint

Medroxyprogesterone Acetate
Plasminogen Activators
Plasminogen Activator Inhibitor 1
Stromal Cells
Urokinase-Type Plasminogen Activator
Antigens
saruplase
Progestins
Assays
Chromogenics
Plasminogen Inactivators
Immunosorbents
Enzyme Precursors
Menstruation
Luteal Phase
Level control
Fibrinolysis
Tissue Plasminogen Activator
Conditioned Culture Medium
Endometrium

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Plasminogen activator activity during decidualization of human endometrial stromal cells is regulated by plasminogen activator inhibitor 1. / Schatz, F.; Aigner, S.; Papp, C.; Tóth-Pál, E.; Hausknecht, V.; Lockwood, C. J.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 80, No. 8, 1995, p. 2504-2510.

Research output: Contribution to journalArticle

@article{20d918bc83984e13824403426857b6d4,
title = "Plasminogen activator activity during decidualization of human endometrial stromal cells is regulated by plasminogen activator inhibitor 1",
abstract = "Progesterone acts on the estradiol (E2)-conditioned human endometrium to induce decidualization of stromal cells. Consistent with these differential hormone actions in vivo, progestins regulate several end points of decidualization in human endometrial stromal cell monolayers and E2 augments the effects of progestin. This study shows that in vitro decidualization of the stromal cells is accompanied by diminished plasminogen activator (PA) expression. Polyacrylamide gel electrophoretic separation after immunoprecipitation of biosynthetically labeled PAs revealed that medroxyprogesterone acetate (MPA) lowered levels of secreted tissue type PA (tPA) at 67 kilodaltons and urokinase type PA (uPA) at 55 kilodaltons. These levels were reduced further by E2 plus MPA despite a lack of response to E2 alone. Although tPA activity was readily measured by a chromogenic assay, detection of uPA activity required prior activation, indicating that uPA is released as the pro-uPA zymogen. Comparisons of levels of immunogenic PAs, as measured by specific enzyme-linked immunosorbent assays, with the corresponding catalytic activities revealed selective progestational inhibition of PA activity vs. antigen after 3 days of experimental incubation. Thus, 10-7 mol/L MPA produced about a 2-fold greater reduction of levels of PA activity than that of its corresponding antigen. More strikingly, 10-8 mol/L E2 plus 10-7 mol/L MPA virtually eliminated both tPA activity (99{\%} inhibition; P <0.005) and uPA activity (93{\%} inhibition; P <0.005); the reductions in levels of the corresponding antigens were only about 50{\%} of the control levels and did not attain statistical significance. Only after 3-6 days of incubation with E2 plus MPA was statistically significant inhibition achieved for immunogenic levels of both tPA (P <0.05) and uPA (P <0.005). Preferential inhibition of levels of PA activities compared with those of the corresponding PA antigens reflects the action of the potent PA inhibitor PAI-1. Thus, the concentration of PAI-1 in the stromal cell-conditioned medium at the end of 0-3 days exceeded those of tPA and uPA, respectively, by 28- and 12-fold in response to MPA and by 52- and 25-fold in response to E2 plus MPA. Extrapolation of these in vitro results to the events of the luteal phase, whose steroidal milieu is mimicked by E2 plus MPA, indicates that decidual cell-derived PAI-1 is a key regulator of proteolytic degradation of extracellular matrix and fibrinolysis during implantation and menstruation.",
author = "F. Schatz and S. Aigner and C. Papp and E. T{\'o}th-P{\'a}l and V. Hausknecht and Lockwood, {C. J.}",
year = "1995",
language = "English",
volume = "80",
pages = "2504--2510",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "8",

}

TY - JOUR

T1 - Plasminogen activator activity during decidualization of human endometrial stromal cells is regulated by plasminogen activator inhibitor 1

AU - Schatz, F.

AU - Aigner, S.

AU - Papp, C.

AU - Tóth-Pál, E.

AU - Hausknecht, V.

AU - Lockwood, C. J.

PY - 1995

Y1 - 1995

N2 - Progesterone acts on the estradiol (E2)-conditioned human endometrium to induce decidualization of stromal cells. Consistent with these differential hormone actions in vivo, progestins regulate several end points of decidualization in human endometrial stromal cell monolayers and E2 augments the effects of progestin. This study shows that in vitro decidualization of the stromal cells is accompanied by diminished plasminogen activator (PA) expression. Polyacrylamide gel electrophoretic separation after immunoprecipitation of biosynthetically labeled PAs revealed that medroxyprogesterone acetate (MPA) lowered levels of secreted tissue type PA (tPA) at 67 kilodaltons and urokinase type PA (uPA) at 55 kilodaltons. These levels were reduced further by E2 plus MPA despite a lack of response to E2 alone. Although tPA activity was readily measured by a chromogenic assay, detection of uPA activity required prior activation, indicating that uPA is released as the pro-uPA zymogen. Comparisons of levels of immunogenic PAs, as measured by specific enzyme-linked immunosorbent assays, with the corresponding catalytic activities revealed selective progestational inhibition of PA activity vs. antigen after 3 days of experimental incubation. Thus, 10-7 mol/L MPA produced about a 2-fold greater reduction of levels of PA activity than that of its corresponding antigen. More strikingly, 10-8 mol/L E2 plus 10-7 mol/L MPA virtually eliminated both tPA activity (99% inhibition; P <0.005) and uPA activity (93% inhibition; P <0.005); the reductions in levels of the corresponding antigens were only about 50% of the control levels and did not attain statistical significance. Only after 3-6 days of incubation with E2 plus MPA was statistically significant inhibition achieved for immunogenic levels of both tPA (P <0.05) and uPA (P <0.005). Preferential inhibition of levels of PA activities compared with those of the corresponding PA antigens reflects the action of the potent PA inhibitor PAI-1. Thus, the concentration of PAI-1 in the stromal cell-conditioned medium at the end of 0-3 days exceeded those of tPA and uPA, respectively, by 28- and 12-fold in response to MPA and by 52- and 25-fold in response to E2 plus MPA. Extrapolation of these in vitro results to the events of the luteal phase, whose steroidal milieu is mimicked by E2 plus MPA, indicates that decidual cell-derived PAI-1 is a key regulator of proteolytic degradation of extracellular matrix and fibrinolysis during implantation and menstruation.

AB - Progesterone acts on the estradiol (E2)-conditioned human endometrium to induce decidualization of stromal cells. Consistent with these differential hormone actions in vivo, progestins regulate several end points of decidualization in human endometrial stromal cell monolayers and E2 augments the effects of progestin. This study shows that in vitro decidualization of the stromal cells is accompanied by diminished plasminogen activator (PA) expression. Polyacrylamide gel electrophoretic separation after immunoprecipitation of biosynthetically labeled PAs revealed that medroxyprogesterone acetate (MPA) lowered levels of secreted tissue type PA (tPA) at 67 kilodaltons and urokinase type PA (uPA) at 55 kilodaltons. These levels were reduced further by E2 plus MPA despite a lack of response to E2 alone. Although tPA activity was readily measured by a chromogenic assay, detection of uPA activity required prior activation, indicating that uPA is released as the pro-uPA zymogen. Comparisons of levels of immunogenic PAs, as measured by specific enzyme-linked immunosorbent assays, with the corresponding catalytic activities revealed selective progestational inhibition of PA activity vs. antigen after 3 days of experimental incubation. Thus, 10-7 mol/L MPA produced about a 2-fold greater reduction of levels of PA activity than that of its corresponding antigen. More strikingly, 10-8 mol/L E2 plus 10-7 mol/L MPA virtually eliminated both tPA activity (99% inhibition; P <0.005) and uPA activity (93% inhibition; P <0.005); the reductions in levels of the corresponding antigens were only about 50% of the control levels and did not attain statistical significance. Only after 3-6 days of incubation with E2 plus MPA was statistically significant inhibition achieved for immunogenic levels of both tPA (P <0.05) and uPA (P <0.005). Preferential inhibition of levels of PA activities compared with those of the corresponding PA antigens reflects the action of the potent PA inhibitor PAI-1. Thus, the concentration of PAI-1 in the stromal cell-conditioned medium at the end of 0-3 days exceeded those of tPA and uPA, respectively, by 28- and 12-fold in response to MPA and by 52- and 25-fold in response to E2 plus MPA. Extrapolation of these in vitro results to the events of the luteal phase, whose steroidal milieu is mimicked by E2 plus MPA, indicates that decidual cell-derived PAI-1 is a key regulator of proteolytic degradation of extracellular matrix and fibrinolysis during implantation and menstruation.

UR - http://www.scopus.com/inward/record.url?scp=0029148407&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029148407&partnerID=8YFLogxK

M3 - Article

C2 - 7629251

AN - SCOPUS:0029148407

VL - 80

SP - 2504

EP - 2510

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 8

ER -