Onapristone (ZK299) and mifepristone (RU486) regulate the messenger RNA and protein expression levels of the progesterone receptor isoforms A and B in the bovine endometrium

Rękawiecki, Robert; Kowalik, Magdalena K.; Kotwica, J.

doi:10.1016/j.theriogenology.2015.03.024

Cited by 9 publications

(9 citation statements)

References 38 publications

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“…Since ER tissue expression is under the control of P4 and E2 [32], it can be assumed that in the absence of estrogen stimulation, ERs are regulated by P4. Progesterone primarily inhibits the tissue ERα expression to prevent the excessive proliferation of endometrial cells [33], but in the face of peripheral E2 deficiency, it also stimulates ER expression, thus increasing tissue sensitivity to E2 [18,34].…”

Section: Discussionmentioning

confidence: 99%

The Influence of Intravaginal Gestagens Treatment on the Morphological Features and Endometrial Steroid Hormone Receptors Content during Anestrus Type II in Dairy Cattle

Trela

Domańska

Kaczmarek

et al. 2022

IJMS

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Background: Gestagens are the most widely used therapy in anestrus type II. The aim of this research is to evaluate the effectiveness of the vaginal progesterone inserts therapy in anestrus type II in cows. Methods: The study was conducted on 33 cows. Progesterone (PR) and estrogen (ER) receptors expression in endometrium was assessed on a molecular level based on mRNA tissue expression. Additionally, blood 17ß-estradiol and progesterone levels were evaluated. Results: A decrease in mRNA expression of A and B PR and ER α was noted in treated and untreated animals. In the treated group, an increase of ERß mRNA expression was observed, while a decreased was found in untreated animals. There was increased PR, ERα and ß expression in endometrial tissue in treated cows, and decreased expression of these factors in untreated cows. In the treated group, recurrence of ovarian cyclicity was noted in 52% of animals and pregnancy was obtained in 34.8% of them, while in the untreated group, recurrence did not occur. In the control group, spontaneous recurrence of ovarian cyclicity was not observed. An increase of PR expression was correlated with increased proliferation of endometrial cells. Conclusions: It seems likely that the endometrium is well developed and ready for placentation after removing the exogenous source of progesterone and preventing the recurrence of cyclicity of ovaries.

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Section: Discussionmentioning

confidence: 99%

The Influence of Intravaginal Gestagens Treatment on the Morphological Features and Endometrial Steroid Hormone Receptors Content during Anestrus Type II in Dairy Cattle

Trela

Domańska

Kaczmarek

et al. 2022

IJMS

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“…Such result was not observed in epithelial cells with similar treatment [ 17 ], probably indicating the specific mechanism of BESC. Progesterone concentration has been found to influence mRNA expressions of both PGRA and PGRB isoforms and thus regulates their effects within bovine endometrial cells [ 35 ]. PGRB is a progesterone-dependent gene activator, whereas PGRA is a weak gene activator and a potent PGRB inhibitor, thereby reducing the effects of progesterone [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

“…Progesterone concentration has been found to influence mRNA expressions of both PGRA and PGRB isoforms and thus regulates their effects within bovine endometrial cells [ 35 ]. PGRB is a progesterone-dependent gene activator, whereas PGRA is a weak gene activator and a potent PGRB inhibitor, thereby reducing the effects of progesterone [ 35 ]. Therefore, the difference between progesterone of 5 ng/mL and progesterone of 1 and 3 ng/mL in regulating IL1B , TNF , and NOS2 mRNA expressions in BESC may be related to the changes in the relative levels of PGR isoforms, and requires further study.…”

Section: Discussionmentioning

confidence: 99%

Anti-inflammatory effects of progesterone through NF-κB and MAPK pathway in lipopolysaccharide- or Escherichia coli-stimulated bovine endometrial stromal cells

et al. 2022

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Postpartum uterine infection in dairy cows is commonly caused by pathogenic bacteria such as Escherichia coli (E. coli). Progesterone elicits immunosuppressive function within bovine endometrium, and has been suggested to be related to postpartum uterine infection. Endometrial stroma is exposed to bacteria due to the disruption of epithelium during parturition, but the effect and mechanism of progesterone on innate immune response of stromal cells has not been reported. This study evaluated the impact of progesterone on inflammatory response of primary endometrial stromal cells stimulated by lipopolysaccharide or heat-killed E. coli. Quantitative PCR analysis revealed that progesterone repressed mRNA induction of IL1B, IL6, TNF, CXCL8, NOS2, and PTGS2 in stromal cells in response to lipopolysaccharide or E. coli challenge. Consistently, Western blot and immunofluorescence staining results showed that progesterone suppressed lipopolysaccharide- or E. coli-induced MAPK and NF-κB activations characterized with decreased phosphorylations of ERK1/2, JNK, P38, IκBα, and P65, and inhibition of P65 nuclear translocation. In unstimulated stromal cells, progesterone alone did not affect the mRNA transcription for IL6, TNF, CXCL8, NOS2, and PTGS2, and the signaling cascade of MAPK and NF-κB, but decreased IL1B mRNA expression. These results revealed that the anti-inflammatory effect of progesterone in lipopolysaccharide- or E. coli-challenged endometrial stromal cells was probably mediated through MAPK and NF-κB pathways.

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“…Next, cells were stimulated for 6 h with P4 (10 −7 M, 10 −6 M, 10 −5 M), E2 (10 −10 M, 10 −9 M, 10 −8 M), P4/E2 (10 −6 /10 −9 M, 10 −5 /10 −8 M), OT (10 −7 M), PGE2 (10 −6 M), PGF2α (10 −6 M), and TNFα (10 −4 M). Doses of factors were based on preliminary studies and previous reports in the literature [ 37 , 38 , 39 ]. Cells were maintained in a humidified atmosphere of 95% O 2 and 5% CO 2 throughout the incubation time.…”

Section: Methodsmentioning

confidence: 99%

Effect of Steroid Hormones, Prostaglandins (E2 and F2α), Oxytocin, and Tumor Necrosis Factor Alpha on Membrane Progesterone (P4) Receptors Gene Expression in Bovine Myometrial Cells

Kowalik

Dobrzyn

Mlynarczuk

et al. 2022

Animals

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Myometrium tissue shows the expression of non-genomic membrane progesterone (P4) receptors, such as progesterone receptor membrane components (PGRMC) 1 and 2 and membrane progestin receptors (mPR) alpha (mPRα), beta (mPRβ), and gamma (mPRγ). Their variable expression in the bovine uterus during the estrous cycle and early pregnancy suggests that ovarian steroids and luteotropic and/or luteolytic factors may regulate the expression of these receptors in the myometrium. Therefore, this study aimed to examine the effect of P4, estradiol (E2), P4 with E2, prostaglandins (PG) E2 and F2α, oxytocin (OT), and tumor necrosis factor α (TNFα) on the gene expression of PGRMC1, PGRMC2, serpine-1 mRNA-binding protein (SERBP1), and mPRα, mPRβ, and mPRγ in bovine myometrial cells from days 6 to 10 and 11 to 16 of the estrous cycle. The PGE2 concentration and mRNA expression were determined by EIA and real-time PCR, respectively. The data indicated that P4 and E2 can affect the mRNA expression of all studied receptors and SERPB1. However, PGE2, OT, and TNFα could only modulate the expression of PGRMC1, PGRMC2, and SERPB1, respectively. Steroids/factors changed the expression of PGRMC and mPR genes depending on the dose, the stage of the estrous cycle, and the types of receptors. This suggests that the local hormonal milieu may influence the activity of these receptors and P4 action in myometrial cells during the estrous cycle.

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Onapristone (ZK299) and mifepristone (RU486) regulate the messenger RNA and protein expression levels of the progesterone receptor isoforms A and B in the bovine endometrium

Cited by 9 publications

References 38 publications

The Influence of Intravaginal Gestagens Treatment on the Morphological Features and Endometrial Steroid Hormone Receptors Content during Anestrus Type II in Dairy Cattle

The Influence of Intravaginal Gestagens Treatment on the Morphological Features and Endometrial Steroid Hormone Receptors Content during Anestrus Type II in Dairy Cattle

Anti-inflammatory effects of progesterone through NF-κB and MAPK pathway in lipopolysaccharide- or Escherichia coli-stimulated bovine endometrial stromal cells

Effect of Steroid Hormones, Prostaglandins (E2 and F2α), Oxytocin, and Tumor Necrosis Factor Alpha on Membrane Progesterone (P4) Receptors Gene Expression in Bovine Myometrial Cells

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