Expression of Progesterone Receptor (PR) A and B Isoforms in Mouse Granulosa Cells: Stage-Dependent PR-Mediated Regulation of Apoptosis and Cell Proliferation1

Shao, Ruijin; Markström, Emilia; Friberg, Peter; Johansson, Martin; Billig, Håkan

doi:10.1095/biolreprod.102.009035

Cited by 85 publications

(88 citation statements)

References 45 publications

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“…However, the regulation of PR proteins has been found to be tissue and cell type specific in female reproductive tissues in vivo (20). Our laboratory has demonstrated that treatment with human chorionic gonadotropin (hCG), mimicking endogenous preovulatory luteinizing hormone surge, induces the levels of PR protein isoforms in periovulatory granulosa cells in mouse ovary (62). Similar observations have been made in ovaries from intact adult mice during the estrous cycle (19) and in humans (22).…”

mentioning

confidence: 59%

Nuclear progesterone receptor A and B isoforms in mouse fallopian tube and uterus: implications for expression, regulation, and cellular function

Shao

Weijdegård²,

Ljungström³

et al. 2006

American Journal of Physiology-Endocrinology and Metabolism

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Progesterone and its interaction with nuclear progesterone receptors (PR) PR-A and PR-B play a critical role in the regulation of female reproductive function in all mammals. However, our knowledge of the regulation and possible cellular function of PR protein isoforms in the fallopian tube and uterus in vivo is still very limited. In the present study, we revealed that equine chorionic gonadotropin (eCG) treatment resulted in a time-dependent increase in expression of both isoforms, reaching a maximal level at 48 h in the fallopian tube. Regulation of PR-A protein expression paralleled that of PR-B protein expression. However, in the uterus PR-B protein levels increased and peaked earlier than PR-A protein levels after eCG treatment. With prolonged exposure to eCG, PR-B protein levels decreased, whereas PR-A protein levels continued to increase. Furthermore, subsequent treatment with human (h)CG decreased the levels of PR protein isoforms in both tissues in parallel with increased endogenous serum progesterone levels. To further elucidate whether progesterone regulates PR protein isoforms, we demonstrated that a time-dependent treatment with progesterone (P4) decreased the expression of PR protein isoforms in both tissues, whereas decreases in p27, cyclin D2, and proliferating cell nuclear antigen protein levels were observed only in the uterus. To define the potential PR-mediated effects on apoptosis, we demonstrated that the PR antagonist treatment increased the levels of PR protein isoforms, induced mitochondrial-associated apoptosis, and decreased in epidermal growth factor (EGF) and EGF receptor protein expression in both tissues. Interestingly, immunohistochemistry indicated that the induction of apoptosis by PR antagonists was predominant in the epithelium, whereas increase in PR protein expression was observed in stromal cells of both tissues. Taken together, these observations suggest that 1) the tissue-specific and hormonal regulation of PR isoform expression in mouse fallopian tube and uterus, where they are potentially involved in regulation of mitochondrial-mediated apoptosis depending on the cellular compartment; and 2) a possible interaction between functional PR protein and growth factor signaling may have a coordinated role for regulating apoptotic process in both tissues in vivo.

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confidence: 59%

Nuclear progesterone receptor A and B isoforms in mouse fallopian tube and uterus: implications for expression, regulation, and cellular function

Shao

Weijdegård²,

Ljungström³

et al. 2006

American Journal of Physiology-Endocrinology and Metabolism

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“…There is some confusion about the relative amounts of each in the corpus luteum. In mice, some authors have found that granulosa cell PR A is higher than PR B but PR is lost during luteinisation (Shao et al 2003), and others have found PR B to be predominant in the granulosa cell and present in the corpus luteum (Gava et al 2004). In the primate corpus luteum, Western blotting suggested that the major PR variant is the B isoform .…”

Section: Discussionmentioning

confidence: 99%

The effect of human chorionic gonadotrophin on the expression of progesterone receptors in human luteal cells in vivo and in vitro

Duncan¹,

Gay²,

Maybin³

2005

Reproduction

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The human corpus luteum expresses genomic progesterone receptors (PRs) suggesting that progesterone may have an autocrine or paracrine role in luteal function. We hypothesised that the reduction in luteal PR reported in the late-luteal phase augmented progesterone withdrawal and had a role in luteolysis. We therefore tested the hypothesis that luteal rescue with human chorionic gonadotrophin (hCG) would maintain PR expression. PR was immunolocalised to different cell types in human corpora lutea (n 5 35) from different stages of the luteal phase and after luteal rescue with exogenous hCG. There was no change in the staining intensity of theca-lutein cell or stromal cell PR throughout the luteal phase or after luteal rescue. In the late-luteal phase, granulosa-lutein cell PR immunostaining was reduced (P < 0.05) but the trend to reduction was also seen after luteal rescue with hCG (P 5 0.055). To further investigate the effect of hCG on granulosa-lutein cell PR expression, an in vitro model system of cultured human luteinised granulosa cells was studied. Cells were cultured for 12 -13 days exposed to different patterns of hCG and aminoglutethamide to manipulate progesterone secretion (P < 0.0001). Expression of PR A/B and PR B isoforms was examined by quantitative real-time RT-PCR. PR A/B mRNA was lower (P < 0.05) after 11 -13 days of culture than after 7 days of culture. This reduction could not be prevented by hCG in the presence (P < 0.05) or absence (P < 0.05) of stimulated progesterone secretion. The expression of PR B mRNA showed a similar pattern (P 5 0.054). Simulated early pregnancy in vivo and hCG treatment of luteinised granulosa cells in vitro did not appear to prevent the down-regulation of PR seen during luteolysis.

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“…Some of these candidates were reported in other species and/or contexts as potential markers of competence, e.g. TNFAIP6 in mouse, porcine CCs (Fulop et al 2003, Nagyova et al 2009), HAS2 in human cumulus GCs (McKenzie et al 2004), PGR in mouse GCs (Shao et al 2003), and INHBA in bovine GCs (Fayad et al 2004).…”

Section: Potential In Vivo Markers Of Oocyte Competencementioning

confidence: 99%

Cumulus cell gene expression following the LH surge in bovine preovulatory follicles: potential early markers of oocyte competence

Assidi¹,

Dieleman²,

Sirard³

2010

Reproduction

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Cumulus cells (CCs) are essential for oocytes to reach full development competency and become fertilized. Many major functional properties of CCs are triggered by gonadotropins and governed by the oocyte. Consequently, cumulus may reflect oocyte quality and is often used for oocyte selection. The most visible function of CCs is their ability for rapid extracellular matrix expansion after the LH surge. Although unexplained, LH induces the final maturation and improves oocyte quality. To study the LH signaling and gene expression cascade patterns close to the germinal vesicle breakdown, bovine CCs collected at 2 h before and 6 h after the LH surge were hybridized to a custom-made microarray to better understand the LH genomic action and find differentially expressed genes associated with the LH-induced oocyte final maturation. Functional genomic analysis of the 141 overexpressed and 161 underexpressed clones was performed according to their molecular functions, gene networks, and cell compartments. Following real-time PCR validation of our gene lists, some interesting pathways associated with the LH genomic action on CCs and their possible roles in oocyte final maturation, ovulation, and fertilization are discussed. A list of early potential markers of oocyte competency in vivo and in vitro is thereafter suggested. These early biomarkers are a preamble to understand the LH molecular pathways that trigger the final oocyte competence acquisition process in bovine.

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Expression of Progesterone Receptor (PR) A and B Isoforms in Mouse Granulosa Cells: Stage-Dependent PR-Mediated Regulation of Apoptosis and Cell Proliferation1

Cited by 85 publications

References 45 publications

Nuclear progesterone receptor A and B isoforms in mouse fallopian tube and uterus: implications for expression, regulation, and cellular function

Nuclear progesterone receptor A and B isoforms in mouse fallopian tube and uterus: implications for expression, regulation, and cellular function

The effect of human chorionic gonadotrophin on the expression of progesterone receptors in human luteal cells in vivo and in vitro

Cumulus cell gene expression following the LH surge in bovine preovulatory follicles: potential early markers of oocyte competence

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