Decreased concentrations and affinities of oestrogen and progesterone receptors of intrauterine tissue in human pregnancy

doi:10.1016/0022-4731(87)90059-8

Journal of Steroid Biochemistry

Volume 26, Issue 4, April 1987, Pages 473-479

https://doi.org/10.1016/0022-4731(87)90059-8 Get rights and content

Abstract

Cytoplasmic and nuclear receptors for oestrogen and progesterone were measured in non-pregnant myometrium and endometrium and compared to concentrations found in decidua of ectopic pregnancy (6–8 weeks gestation) and therapeutic abortions (8–16 weeks). Amnion, chorion, placenta, decidua and myometrium at full term pregnancy were also assayed for the same receptors. High affinity binding was confirmed in the non-pregnant tissue; in early pregnancy, decreases in concentrations of cytoplasmic receptors were demonstrated, these decreases becoming more marked as pregnancy progressed in the 1st trimester. Nuclear receptor concentrations were not significantly different. Significant decreases in the occurrence of positive receptors with the progression of pregnancy were also demonstrated for cytoplasmic and nuclear oestrogen and nuclear progesterone receptors. Tissue at full term pregnancy had no detectable receptors, irrespective of whether the patients were in labour or not. Increasing the range of the labelled steroids failed to demonstrate any low affinity binding sites and pre-assay removal of endogenous hormones also had no effect on receptor status. When endogenous hormones were removed, displaceable binding was demonstrated in the presence of excess unlabelled ligand. However, this binding did not conform with receptor dynamics on Scatchard analysis. Heating the cytosol prior to assay or failure to remove endogenous steroid hormones eliminated this binding. Cytosolic oestrogen and progesterone levels increased significantly in the decidua of therapeutic abortions, whilst term pregnant tissue had the highest concentration of endogenous hormones.

References (28)

A.I. Csapo et al.
The significance of human corpus luteum in pregnancy maintenance. I. Preliminary studies
Am. J. Obstet. Gynec.
(1972)
A.I. Csapo et al.
Effects of luteectomy and progesterone replacement therapy in early pregnancy patients
Am. J. Obstet. Gynec.
(1973)
L. Kovacs et al.
Termination of very early pregnancy by RU 486—an antiprogestational compound
Contraception
(1984)
A. Turnbull et al.
Significant fall in progesterone and rise in oestradiol levels in human peripheral plasma before onset of labour
Lancet
(1974)
A.I. Csapo et al.
Peripheral plasma progesterone levels during human pregnancy and labor
Am. J. Obstet. Gynec.
(1971)
F. Fuchs et al.
Treatment of threatened premature labour with large doses of progesterone
Br. J. Obstet. Gynaec.
(1960)
R. Erny et al.
The effects of oral administration of progesterone for premature labor
Am. J. Obstet. Gynec.
(1986)
M.A. Younes et al.
Estradiol and progesterone binding in human term placenta
Am. J. Obstet. Gynec.
(1981)
O.H. Lowry et al.
Protein measurement with the Folin phenol reagent
J. biol. Chem.
(1951)
C. Levy et al.
Estradiol and progesterone receptors in human endometrium: normal and abnormal menstrual cycles and early pregnancy
Am. J. Obstet. Gynec.
(1980)

T. Tamaya et al.

Relation between steroid receptor levels and prolactin level in the decidua of early human pregnancy

Fert. Steril.

(1985)

H.A.M. Vervest et al.

Preliminary results with the antiprogestational compound RU 486 (mifepristone) for interruption of early pregnancy

Fert. Steril.

(1985)

J.M. Bassett et al.

The concentration of progesterone in the peripheral plasma of the pregnant ewe

J. Endocr.

(1969)

R.S. Mather et al.

Progesterone, 17-hydroxyprogesterone, estradiol and estriol in late pregnancy and labor

Am. J. Obstet. Gynec.

(1980)

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Characterization of progesterone receptor isoform expression in fetal membranes
2006, American Journal of Obstetrics and Gynecology
To quantify expression of progesterone receptor (PR) messenger RNA (mRNA) isoforms in fetal membranes, and to determine whether these levels change in culture.
Placentas from women undergoing term cesarean delivery before labor were collected. Layers of amnion, chorion, and decidua were separated manually, enzymatically digested, and separated further with the use of a density gradient. RNA was extracted immediately and after culture for 48 hours, then analyzed by quantitative reverse transcription polymerase chain reaction for PR-A, PR-B, and β-2 microglobulin mRNA expression. Separation of cell types was confirmed by immunohistochemistry.
PR isoform expression was identified in fetal membranes, with levels highest in decidua and below the limits of detection in amnion. The ratio of PR-A/PR-B mRNA was not significantly different between cell layers. PR mRNA isoform levels did not differ significantly in fresh versus cultured cells.
Quantitative reverse transcription polymerase chain reaction was used to quantitate expression of PR mRNA isoforms in cells of fetal membranes and to validate systems for further study of PR with respect to inflammation, infection, and preterm delivery.
Progesterone receptor isoform (A/B) ratio of human fetal membranes increases during term parturition
2005, American Journal of Obstetrics and Gynecology
Citation Excerpt :
Studies of the expression of PR in the human fetal membranes have shown conflicting results. Earlier data obtained using an exchange assay method, high-affinity binding assay, or enzyme immunoassay demonstrated that there was no detectable PR in the fetal membranes at term.13-15 However, Chibbar et al recently demonstrated that mRNA for the PR was present in human amnion and chorio-decidua using a ribonuclease protection assay.7
The role of progesterone in the control of human parturition remains unsettled. Because there is no systemic progesterone withdrawal before the onset of labor, a ‘functional progesterone withdrawal’ has been proposed to be operative before human parturition. This may be accomplished by a change in the density of the progesterone receptor (PR) isoforms in myometrium and fetal membranes. The purpose of our study was to determine if spontaneous term labor is associated with changes of PR isoforms (PR-A and PR-B) in the fetal membranes.
Fetal membranes were obtained from women undergoing elective cesarean delivery at term (not in labor group), and from women with a vaginal delivery (labor group). The expression of PR isoforms was assessed by Western blot analysis of amnion and chorio-decidua. Densitometric analysis of PR-A/PR-B ratio was performed. Immunohistochemistry with specific antibodies to PR-A and PR-B was done. Nonparametric statistics were used for analysis.
1) The predominant isoform of PR in women not in labor was PR-B, and PR-A in patients in labor. The ratio of PR-A/PR-B in fetal membranes was significantly higher in women in labor than in those not in labor (for amnion, median 4.3, range [0.9-8.4] vs median 0.4, range [0.3-2.6], P < .001; for chorio-decidua, median 2.0, range [1.1-19.2] vs median 1.2, range [0.1-2.0], P < .05). 2) Fetal membranes expressed both types of PR. 3) Immunohistochemistry showed the presence of PR-A and PR-B in the cytoplasm of amnion epithelial cells, chorion trophoblast, and decidual cells.
Human parturition at term is associated with changes in PR isoforms in the fetal membranes and, thus, a local ‘functional progesterone withdrawal’ may operate in human parturition through this mechanism.
Reduced binding of progesterone receptor to its nuclear response element after human labor onset
2001, American Journal of Obstetrics and Gynecology
Objective: There is indirect evidence of decreased progesterone-activated transcription after human labor onset. Binding of the progesterone receptor to its response element is a prerequisite of progesterone-activated transcription. We established an assay to investigate whether there is reduced binding of progesterone receptor to its nuclear response element after, compared with before, labor onset. Study Design: The binding of progesterone receptor from the decidua to its nuclear response element was measured in gel shift assays. Tissues from 52 patients who were term, preterm, in labor, and not in labor were compared. Results: A 9-fold decrease in progesterone receptor binding to its response element was observed in tissues obtained after, compared with before, the onset of labor (P =.0008). In both preterm and term not-in-labor tissues, binding was higher than for in-labor tissues (P =.0172 for preterm; P =.0147 for term, Mann-Whitney U test). Conclusion: These findings provide a mechanism for the effective withdrawal of progesterone in human parturition. (Am J Obstet Gynecol 2001;185:579-85.)
Phthalic acid mimics 17β-estradiol actions in WISH cells
2001, Toxicology Letters
The object of this study was to evaluate whether phthalic acid, which is one of the metabolites of phthalic acid esters, exerts estrogenic actions in WISH cells, an immortalized cell line derived from human amniotic tissue. Our data demonstrate that phthalic acid (i) displaces [³H]estradiol from its binding sites, (ii) enhances the intracellular cyclic AMP concentration, without influencing adenylyl cyclase activity, (iii) stimulates or inhibits prostaglandin output, probably depending on the intracellular nucleotide level. The effects on prostanoid release are counteracted by addition of the protein-synthesis inhibitor cycloheximide, or when the diffusion of phthalic acid through the cell membrane is prevented. On the basis of our previous demonstration, that 17β-estradiol exerts similar effects in WISH cells, we suggest that the molecular mechanisms underlying phthalic acid and steroid-hormone responses in this cell line are the same. This is the first demonstration that phthalic acid binds to the estrogen receptor with high affinity and mimics the hormone physiological actions.
Interleukin-8 synthesis and the onset of labor
1995, Obstetrics and Gynecology
Objective: To examine the role of cytokines in cervical dilation.
Methods: In 55 patients undergoing cesarean delivery, we took samples from the lower uterine segment, the decidua, and the membranes. We determined the concentrations of interleukin (IL)-2, IL-8, tumor necrosis factor-α, matrix metalloproteinase (MMP)-8, and MMP-9 in the different tissues.
Results: Depending on the state of labor, we observed a significant increase (P < .001) in IL-8 concentrations in the lower uterine segment. The leukocyte enzymes MMP-8 and MMP-9 were highly significantly correlated with the IL-8 concentrations.
Conclusion: Interleukin-8 is critically involved in the process of parturition in humans. Interleukin-8 concentrations in the myometrium, decidua, and membranes correlated strongly with the observed MMP-8 and MMP-9 concentrations.
Enzyme immunoassay of oestrogen and progesterone receptors in uterine and intrauterine tissue during human pregnancy and labour
1990, Journal of Steroid Biochemistry and Molecular Biology
Oestrogen and progesterone receptors were studied in the non-pregnant state, in early pregnancy and at term using monoclonal antibody enzyme immunoassays. Receptors for both steroids were found in tissues from non-pregnant patients and patients in early pregnancy. At term oestrogen receptors were undetectable in all tissues studied. Progesterone receptors were undetectable in chorion, amnion and placenta at term, while present in extremely low concentrations in decidua and myometrium.

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Decreased concentrations and affinities of oestrogen and progesterone receptors of intrauterine tissue in human pregnancy

Abstract

Am. J. Obstet. Gynec.

Am. J. Obstet. Gynec.

Contraception

Lancet

Am. J. Obstet. Gynec.

Br. J. Obstet. Gynaec.

Am. J. Obstet. Gynec.

Am. J. Obstet. Gynec.

J. biol. Chem.

Am. J. Obstet. Gynec.

Fert. Steril.

Fert. Steril.

The concentration of progesterone in the peripheral plasma of the pregnant ewe

J. Endocr.

Progesterone, 17-hydroxyprogesterone, estradiol and estriol in late pregnancy and labor

Am. J. Obstet. Gynec.