Expression of Progesterone Receptors A and B in the Mouse Ovary during the Estrous Cycle

Gava, Natalie; Clarke, Christine L.; Arnett-Mansfield, Rebecca L.; deFazio, Anna

doi:10.1210/en.2004-0212

Cited by 68 publications

(59 citation statements)

References 49 publications

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“…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). In addition, the developmental time course of PR mRNA and protein expression has been extensively studied in the uterus by use of either ovariectomized animals (a background devoid of endogenous steroid hormones) treated with selected steroid hormones (27,30,31,70) or intact adult rats during the estrous cycle (46).…”

mentioning

confidence: 68%

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: 68%

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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“…[43][44][45] Our previous studies suggested that UCH-L1 and UCH-L3, despite their high sequence homology, 12 have distinct expression patterns and differential function in testis and epididymis. 9,11 Here we show that these two proteins have distinct distributions: UCH-L1 is exclusively expressed on the plasma membrane of oocytes and embryos, whereas UCH-L3 is diffusely expressed in the cytoplasm (Figures 1B and 2B).…”

Section: Discussionmentioning

confidence: 99%

Localization of Ubiquitin C-Terminal Hydrolase L1 in Mouse Ova and Its Function in the Plasma Membrane to Block Polyspermy

Sekiguchi

Kwon

Yoshida

et al. 2006

The American Journal of Pathology

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Protein degradation is essential for oogenesis and embryogenesis. The ubiquitin-proteasome system regulates many cellular processes via the rapid degradation of specific proteins. Ubiquitin carboxylterminal hydrolase L1 (UCH-L1) is exclusively expressed in neurons , testis , ovary , and placenta , each of which has unique biological activities. However , the functional role of UCH-L1 in mouse oocytes remains unknown. Here , we report the expression pattern of UCH-L1 and its isozyme UCH-L3 in mouse ovaries and embryos. Using immunocytochemistry , UCH-L1 was selectively detected on the plasma membrane , whereas UCH-L3 was mainly detected in the cytoplasm, suggesting that these isozymes have distinct functions in mouse eggs. To further investigate the functional role of UCH-L1 in mouse eggs, we analyzed the fertilization rate of UCH-L1-deficient ova of gad female mice. Female gad mice had a significantly increased rate of polyspermy in in vitro fertilization assays, although the rate of fertilization did not differ significantly from wild-type mice. In addition, the litter size of gad female mice was significantly reduced compared with wild-type mice. These results may identify UCH-L1 as a candidate for a sperm-oocyte interactive binding or fusion protein on the plasma membrane that functions during the block to polyspermy in mouse oocytes.

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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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Expression of Progesterone Receptors A and B in the Mouse Ovary during the Estrous Cycle

Cited by 68 publications

References 49 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

Localization of Ubiquitin C-Terminal Hydrolase L1 in Mouse Ova and Its Function in the Plasma Membrane to Block Polyspermy

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

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