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Prostaglandin receptors EP and FP are regulated by estradiol and progesterone in the uterus of ovariectomized rats.

Blesson CS, Büttner E, Masironi B, Sahlin L - Reprod. Biol. Endocrinol. (2012)

Bottom Line: Our results showed that all mRNAs and proteins of EPs and FP are expressed in the rat uterus.EP1 and EP3 are upregulated by the combination of estradiol and progesterone.Thus, our observations indicate that estradiol and progesterone regulate the mRNA and protein expression of EPs and FP in a receptor and tissue specific way.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division for Reproductive Endocrinology and the Paediatric Endocrinology Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden. Blesson.Selvanesan@ki.se

ABSTRACT

Background: Prostaglandins are important for female reproduction. Prostaglandin-E2 acts via four different receptor subtypes, EP1, EP2, EP3 and EP4 whereas prostaglandin-F2alpha acts through FP. The functions of prostaglandins depend on the expression of their receptors in different uterine cell types. Our aim was to investigate the expression of EPs and FP in rat uterus and to identify the regulation by estradiol, progesterone and estrogen receptor (ER) selective agonists.

Methods: We performed four different rat experiments involving treatments with estradiol, progesterone and ER agonists. Real-time PCR and immunohistochemistry were employed to evaluate receptor expression.

Results: Our results showed that all mRNAs and proteins of EPs and FP are expressed in the rat uterus. The expression pattern and intensity of immunostaining vary between different cell types and treatments. The mRNA expression of all EPs and FP are downregulated by estradiol and the ERalpha specific agonist PPT, whereas the ERbeta specific agonist DPN downregulates only EP2 and EP4. The protein expression however, showed an increase in EP2 and EP3 after estradiol treatment. When treated with estradiol and progesterone in combination, the expressions of EP1 and EP3 are upregulated.

Conclusions: Regulation of EPs and FP expression by estradiol appears to be mainly modulated via ERalpha for EP1, EP3 and FP, while EP2 and EP4 also are affected by the ERbeta selective ligand. Our immunohistochemical data shows a cell specific regulation of prostaglandin receptors under the influence of ovarian steroids, where EP2 is estrogen regulated in all uterine tissues examined. EP1 and EP3 are upregulated by the combination of estradiol and progesterone. Thus, our observations indicate that estradiol and progesterone regulate the mRNA and protein expression of EPs and FP in a receptor and tissue specific way.

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Regulation of EP2 and EP3 protein by different doses of estradiol. Results from manual scoring of EP2 and EP3 immunostaining in different uterine cell types when treated with different doses of estradiol (E2). Box and whisker plots representing the median value with 50% of all data falling within the box. The whiskers extend to the 5th and 95th percentiles. Bars with asterisks are significantly (P < 0.05) different from the control group (OvxC). LE- luminal epithelium, GE- glandular epithelium.
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Figure 3: Regulation of EP2 and EP3 protein by different doses of estradiol. Results from manual scoring of EP2 and EP3 immunostaining in different uterine cell types when treated with different doses of estradiol (E2). Box and whisker plots representing the median value with 50% of all data falling within the box. The whiskers extend to the 5th and 95th percentiles. Bars with asterisks are significantly (P < 0.05) different from the control group (OvxC). LE- luminal epithelium, GE- glandular epithelium.

Mentions: Real-time PCR data showed that E2 downregulates the expression of EPs and FP mRNAs in the uterus (Figure 1). The decrease was significant (p < 0.05) for EP1 and EP4 at low dose treatment (1.0 μg); EP2, EP3 and FP at mid dose (2.5 μg) and for the expression of all receptors when treated with the highest dose (5.0 μg). However, results from immunohistochemistry showed that there is an increase in the immunostaining of EP2 and EP3 following E2 treatments (Figure 2 and 3). There is an increase (p < 0.05) in the immunostaining of EP2 when treated with 5.0 μg of E2 in luminal epithelium, glandular epithelium, stroma and myometrium when compared to controls. In blood vessels a similar tendency was seen. EP3 immunostaining was increased (p < 0.05) in stroma and myometrium when treated with 2.5 μg of E2 (Figure 3). Corresponding tendencies could be observed in stroma and myometrium of study 3 after a comparable E2 treatment. Luminal epithelium, glandular epithelium and blood vessels also show similar trends. Immunostaining of the EP1, EP4 and FP receptors did not show any significant differences (data not shown).


Prostaglandin receptors EP and FP are regulated by estradiol and progesterone in the uterus of ovariectomized rats.

Blesson CS, Büttner E, Masironi B, Sahlin L - Reprod. Biol. Endocrinol. (2012)

Regulation of EP2 and EP3 protein by different doses of estradiol. Results from manual scoring of EP2 and EP3 immunostaining in different uterine cell types when treated with different doses of estradiol (E2). Box and whisker plots representing the median value with 50% of all data falling within the box. The whiskers extend to the 5th and 95th percentiles. Bars with asterisks are significantly (P < 0.05) different from the control group (OvxC). LE- luminal epithelium, GE- glandular epithelium.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3278370&req=5

Figure 3: Regulation of EP2 and EP3 protein by different doses of estradiol. Results from manual scoring of EP2 and EP3 immunostaining in different uterine cell types when treated with different doses of estradiol (E2). Box and whisker plots representing the median value with 50% of all data falling within the box. The whiskers extend to the 5th and 95th percentiles. Bars with asterisks are significantly (P < 0.05) different from the control group (OvxC). LE- luminal epithelium, GE- glandular epithelium.
Mentions: Real-time PCR data showed that E2 downregulates the expression of EPs and FP mRNAs in the uterus (Figure 1). The decrease was significant (p < 0.05) for EP1 and EP4 at low dose treatment (1.0 μg); EP2, EP3 and FP at mid dose (2.5 μg) and for the expression of all receptors when treated with the highest dose (5.0 μg). However, results from immunohistochemistry showed that there is an increase in the immunostaining of EP2 and EP3 following E2 treatments (Figure 2 and 3). There is an increase (p < 0.05) in the immunostaining of EP2 when treated with 5.0 μg of E2 in luminal epithelium, glandular epithelium, stroma and myometrium when compared to controls. In blood vessels a similar tendency was seen. EP3 immunostaining was increased (p < 0.05) in stroma and myometrium when treated with 2.5 μg of E2 (Figure 3). Corresponding tendencies could be observed in stroma and myometrium of study 3 after a comparable E2 treatment. Luminal epithelium, glandular epithelium and blood vessels also show similar trends. Immunostaining of the EP1, EP4 and FP receptors did not show any significant differences (data not shown).

Bottom Line: Our results showed that all mRNAs and proteins of EPs and FP are expressed in the rat uterus.EP1 and EP3 are upregulated by the combination of estradiol and progesterone.Thus, our observations indicate that estradiol and progesterone regulate the mRNA and protein expression of EPs and FP in a receptor and tissue specific way.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division for Reproductive Endocrinology and the Paediatric Endocrinology Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden. Blesson.Selvanesan@ki.se

ABSTRACT

Background: Prostaglandins are important for female reproduction. Prostaglandin-E2 acts via four different receptor subtypes, EP1, EP2, EP3 and EP4 whereas prostaglandin-F2alpha acts through FP. The functions of prostaglandins depend on the expression of their receptors in different uterine cell types. Our aim was to investigate the expression of EPs and FP in rat uterus and to identify the regulation by estradiol, progesterone and estrogen receptor (ER) selective agonists.

Methods: We performed four different rat experiments involving treatments with estradiol, progesterone and ER agonists. Real-time PCR and immunohistochemistry were employed to evaluate receptor expression.

Results: Our results showed that all mRNAs and proteins of EPs and FP are expressed in the rat uterus. The expression pattern and intensity of immunostaining vary between different cell types and treatments. The mRNA expression of all EPs and FP are downregulated by estradiol and the ERalpha specific agonist PPT, whereas the ERbeta specific agonist DPN downregulates only EP2 and EP4. The protein expression however, showed an increase in EP2 and EP3 after estradiol treatment. When treated with estradiol and progesterone in combination, the expressions of EP1 and EP3 are upregulated.

Conclusions: Regulation of EPs and FP expression by estradiol appears to be mainly modulated via ERalpha for EP1, EP3 and FP, while EP2 and EP4 also are affected by the ERbeta selective ligand. Our immunohistochemical data shows a cell specific regulation of prostaglandin receptors under the influence of ovarian steroids, where EP2 is estrogen regulated in all uterine tissues examined. EP1 and EP3 are upregulated by the combination of estradiol and progesterone. Thus, our observations indicate that estradiol and progesterone regulate the mRNA and protein expression of EPs and FP in a receptor and tissue specific way.

Show MeSH