C J Lockwood1, C Stocco, W Murk, U A Kayisli, E F Funai, F Schatz. 1. Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06510, USA.
Abstract
CONTEXT: Unchanging plasma progesterone (P4) levels suggest that human labor is initiated by reduced P4 receptor (PR) expression, which elicits functional P4 withdrawal. The glucocorticoid receptor (GR) is also implicated in this process. OBJECTIVE: Our objective was to compare PR and GR staining in human decidual cells (DCs) and interstitial trophoblasts (ITs) of gestational age-matched pre- and postcontraction specimens and to evaluate steroid effects on PR and GR expression in human DC cultures. INTERVENTIONS AND MAIN OUTCOME MEASURES: Decidua basalis and parietalis sections were immunostained for PR or GR and then for the cytoplasmic DC and IT markers vimentin and cytokeratin. Western blotting measured PR and GR levels in nuclear extracts of cultured leukocyte-free term DCs after incubation with estradiol-17beta (E2) with or without medroxyprogesterone acetate (MPA). RESULTS: PR histological scores (HSCOREs) were significantly higher in DC nuclei from pre- vs. post-uterine-contraction decidua basalis and parietalis sections with PR immunostaining absent from ITs. In contrast, immunoreactive GR was localized in IT and DC nuclei. GR HSCORES were significantly higher in ITs than DCs but similar in pre- vs. post-uterine-contraction specimens. In term DC monolayers, PR-A and PR-B were enhanced by E2 and inhibited by MPA, whereas E2 plus MPA produced intermediate PR expression. The GR was constitutively expressed. CONCLUSIONS: In post- vs. pre-uterine-contraction specimens, significantly lower HSCOREs in DC nuclei, but not IT, and unchanging GR levels in DCs and ITs suggest that functional P4 withdrawal may occur in DCs and is unlikely to involve the GR. Nuclear extracts from DC monolayer cultures express steroid-regulated PR-A and PR-B and constitutive GR.
CONTEXT: Unchanging plasma progesterone (P4) levels suggest that humanlabor is initiated by reduced P4 receptor (PR) expression, which elicits functional P4 withdrawal. The glucocorticoid receptor (GR) is also implicated in this process. OBJECTIVE: Our objective was to compare PR and GR staining in human decidual cells (DCs) and interstitial trophoblasts (ITs) of gestational age-matched pre- and postcontraction specimens and to evaluate steroid effects on PR and GR expression in humanDC cultures. INTERVENTIONS AND MAIN OUTCOME MEASURES: Decidua basalis and parietalis sections were immunostained for PR or GR and then for the cytoplasmic DC and IT markers vimentin and cytokeratin. Western blotting measured PR and GR levels in nuclear extracts of cultured leukocyte-free term DCs after incubation with estradiol-17beta (E2) with or without medroxyprogesterone acetate (MPA). RESULTS: PR histological scores (HSCOREs) were significantly higher in DC nuclei from pre- vs. post-uterine-contraction decidua basalis and parietalis sections with PR immunostaining absent from ITs. In contrast, immunoreactive GR was localized in IT and DC nuclei. GR HSCORES were significantly higher in ITs than DCs but similar in pre- vs. post-uterine-contraction specimens. In term DC monolayers, PR-A and PR-B were enhanced by E2 and inhibited by MPA, whereas E2 plus MPA produced intermediate PR expression. The GR was constitutively expressed. CONCLUSIONS: In post- vs. pre-uterine-contraction specimens, significantly lower HSCOREs in DC nuclei, but not IT, and unchanging GR levels in DCs and ITs suggest that functional P4 withdrawal may occur in DCs and is unlikely to involve the GR. Nuclear extracts from DC monolayer cultures express steroid-regulated PR-A and PR-B and constitutive GR.
Authors: Amy A Merlino; Toni N Welsh; Huiqing Tan; Li Juan Yi; Vernon Cannon; Brian M Mercer; Sam Mesiano Journal: J Clin Endocrinol Metab Date: 2007-03-06 Impact factor: 5.958
Authors: Charles J Lockwood; Felice Arcuri; Paolo Toti; Claudio De Felice; Graciela Krikun; Seth Guller; Lynn F Buchwalder; Frederick Schatz Journal: Am J Pathol Date: 2006-10 Impact factor: 4.307
Authors: C J Lockwood; W Murk; U A Kayisli; L F Buchwalder; S-T Huang; E F Funai; G Krikun; F Schatz Journal: J Clin Endocrinol Metab Date: 2009-03-10 Impact factor: 5.958
Authors: Sam Mesiano; Eng-Cheng Chan; John T Fitter; Kenneth Kwek; George Yeo; Roger Smith Journal: J Clin Endocrinol Metab Date: 2002-06 Impact factor: 5.958
Authors: Amy Merlino; Toni Welsh; Tan Erdonmez; Gemma Madsen; Tamas Zakar; Roger Smith; Brian Mercer; Sam Mesiano Journal: Reprod Sci Date: 2009-02-05 Impact factor: 3.060
Authors: Charles J Lockwood; Umit A Kayisli; Carlos Stocco; William Murk; Emre Vatandaslar; Lynn F Buchwalder; Frederick Schatz Journal: Am J Pathol Date: 2012-10-09 Impact factor: 4.307
Authors: William E Ackerman; Taryn L Summerfield; Sam Mesiano; Frederick Schatz; Charles J Lockwood; Douglas A Kniss Journal: Reprod Sci Date: 2015-08-04 Impact factor: 3.060