Responsivity to PGE2 labor induction involves concomitant differential prostaglandin E receptor gene expression in cervix and myometrium

Konopka, Cristine Kolling; Glanzner, Werner Giehl; Rigo, M.; Rovani, Monique Tomazele; Comim, Fábio Vasconcellos; Gonçalves, P. B. D.; Morais, Edson Nunes de; Antoniazzi, Alfredo Q.; Mello, Carlos Fernando; Cruz, I. B. M.

doi:10.4238/2015.september.9.25

Cited by 10 publications

(6 citation statements)

References 32 publications

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“…Prostaglandins are involved in sex hormone signaling, and sex-dependent differential PGE 2 production, response and receptor expression has previously been reported [45-47], so differences between male and female PGE 2 levels are not unexpected. This provides a possible explanation for our result showing significantly lower PGE 2 concentrations in female, but not male RRMS subjects, compared to HC and SPMS.…”

Section: Discussionmentioning

confidence: 99%

Lipoic Acid Stimulates cAMP Production in Healthy Control and Secondary Progressive MS Subjects

et al. 2017

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Lipoic acid (LA) exhibits antioxidant and anti-inflammatory properties; supplementation reduces disease severity and T lymphocyte migration into the central nervous system in a murine model of multiple sclerosis (MS), and administration in secondary progressive MS (SPMS) subjects reduces brain atrophy compared to placebo. The mechanism of action (MOA) of LA's efficacy in suppression of MS pathology is incompletely understood. LA stimulates production of the immunomodulator cyclic AMP (cAMP) in vitro. To determine whether cAMP could be involved in the MOA of LA in vivo, we performed a clinical trial to examine whether LA stimulates cAMP production in healthy control and MS subjects, and whether there are differences in the bioavailability of LA between groups. We administered 1200 mg of oral LA to healthy control, relapsing remitting MS (RRMS) and SPMS subjects, and measured plasma LA and cAMP levels in peripheral blood mononuclear cells (PBMCs). There were no significant differences between the groups in pharmacokinetic (PK) parameters. Healthy and SPMS subjects had increased cAMP at 2 and 4 h post-LA treatment compared to baseline, while RRMS subjects showed decreases in cAMP. Additionally, plasma concentrations of prostaglandin E2 (PGE, a known cAMP stimulator) were significantly lower in female RRMS subjects compared to female HC and SPMS subjects 4 h after LA ingestion. These data indicate that cAMP could be part of the MOA of LA in SPMS, and that there is a divergent response to LA in RRMS subjects that may have implications in the efficacy of immunomodulatory drugs. This clinical trial, "Defining the Anti-inflammatory Role of Lipoic Acid in Multiple Sclerosis," NCT00997438, is registered at https://clinicaltrials.gov/ct2/show/record/NCT00997438 .

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Section: Discussionmentioning

confidence: 99%

Lipoic Acid Stimulates cAMP Production in Healthy Control and Secondary Progressive MS Subjects

et al. 2017

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“…For example, expression of EP2 receptor (smooth muscle relaxant receptors) in myometrium is maintained throughout the pregnancy, contributing to quiescence, but reduced at term in labor. EP3 receptors (smooth muscle contractile receptors), on the other hand, are increased leading to labor at term and mobilized more toward the lower segment myometrium, contributing to smooth muscle contractions during labor (38,51,52). The binding constant for PGE 2 to EP3 receptors is about 1 nM (53).…”

Section: "Inflammatory" Lipid Mediator and Receptor Sufficiency Yet mentioning

confidence: 99%

Non-inflammatory Physiology of “Inflammatory” Mediators – Unalamation, a New Paradigm

Maddipati

2020

Front. Immunol.

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Many small molecules (mostly lipids derived from polyunsaturated fatty acids) and proteins (e. g., cytokines and chemokines) are labeled as inflammatory mediators for their role in eliciting physiological responses to injury. While acute inflammatory events are controlled by anti-inflammatory drugs, lasting damage to the tissues as a result of persistent inflammation is increasingly viewed as the root cause of many chronic diseases that include cardiovascular, neurological, and metabolic disorders, rheumatoid arthritis, and cancer. Interestingly, some of the "inflammatory" mediators also participate in normal developmental physiology without eliciting inflammation. Anti-inflammatory drugs that target the biosynthesis of these mediators are too indiscriminate to distinguish their two divergent physiological roles. A more precise definition of these two physiological processes partaken by the "inflammatory" mediators is warranted to identify their differences. The new paradigm is named "unalamation" (' e 'n' e lAmāSH(e)n) to distinguish from inflammation and to identify appropriate intervention strategies to mitigate inflammation associated pathophysiology without affecting the normal developmental physiology.

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“…Myometrial/endometrial EP3 and FP expressions controlling myometrial activity have been presented in previous studies (Palliser et al, 2006;Ma et al, 1999;Konopka et al, 2015). Nevertheless undetect- able or extremely low level of EP1 has not been taken into consideration either in spontaneous or dexamethasone-induced parturition (Ma et al, 1999;Konopka et al, 2015). Significant upregulation of cotyledonary FP, EP1 and EP3 expressions in AG ewes could be the reason for decreased pathologies during parturition.…”

Section: Discussionmentioning

confidence: 95%

“…The clinical efficiency of aglepristone having less parturition pathology in pregnancy toxemia could associate with cotyledonary expression of prostaglandin receptors. Myometrial/endometrial EP3 and FP expressions controlling myometrial activity have been presented in previous studies (Palliser et al, 2006;Ma et al, 1999;Konopka et al, 2015). Nevertheless undetect- able or extremely low level of EP1 has not been taken into consideration either in spontaneous or dexamethasone-induced parturition (Ma et al, 1999;Konopka et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Expression of steroidogenic enzymes in placentome of ewes with pregnancy toxemia after two parturition induction methods

Özalp,

Ortaç,

Bozkurt

et al. 2023

J Hellenic Vet Med Soc

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The regulation pattern of important enzymes in placental steroidogenesis and prostaglandins in ewes with pregnancy toxemia is reviewed. The alterations of gene expressions after the administration of aglepristone and dexamethasone are also discussed. Four healthy and 22 ewes with pregnancy toxemia were included to the study. Group AG (n=9) and Group DEX (n=9) in which ewes were injected twice with 10 mg/kg of aglepristone and once with 5 ml dexamethasone, respectively; whereas negative control [Group CG (n=4)] and pregnancy toxemia [Group PT (n=4)] groups received no treatment for parturition induction. Placentomes were collected either right after parturition or C-section. mRNA extraction from total placentome, caruncle, cotyledon and caruncle part of placentomes was carried out and Real-Time PCR was performed. Serum samples were collected and cortisol, PGFM, PGE2 and estrone sulfate concentrations were measured after treatments until parturition. The lowest mRNA expressions of steroidogenic enzymes were detected in group PT. Interestingly similar expression pattern of steroidogenic enzymes in group AG was as similar as group PT. No difference was found in expressions of 3βHSD and CYP19. PTGS2/COX2 and PGFS mRNA expressions were statistically different between groups AG-DEX and in caruncle between groups, respectively (P<0.005). Significant difference could clearly be observed in EP3 expression in caruncle of DEX and AG compared to CG (P<0.005); however PTGES, EP1, EP2 and EP4 expressions were not statistically different among groups (P>0,05). Ostrone sulfate, PGE2 and PGFM concentrations were statistically different according to the sampling time between groups however no difference was observed in cortisol. The present study has suggests that the endocrinologic pathway controlling parturition is clearly different in ewes with pregnancy toxemia. Spontaneous parturition could occur as a consequence of immune and inflammatory processes, which could be activated by by-products of fat metabolism. Dexamethasone applications has mimicked normal parturition, however the gene expression regulations, controlling uterine contractions, are observed as similar as group PT. Probably expressions of EP1 and tissue-specific counter-expressions of cervical EP genes could refer the pathogenesis of insufficient cervical dilatation, observed in pregnancy toxemia and dexamethsone applications.

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Responsivity to PGE2 labor induction involves concomitant differential prostaglandin E receptor gene expression in cervix and myometrium

Cited by 10 publications

References 32 publications

Lipoic Acid Stimulates cAMP Production in Healthy Control and Secondary Progressive MS Subjects

Lipoic Acid Stimulates cAMP Production in Healthy Control and Secondary Progressive MS Subjects

Non-inflammatory Physiology of “Inflammatory” Mediators – Unalamation, a New Paradigm

Expression of steroidogenic enzymes in placentome of ewes with pregnancy toxemia after two parturition induction methods

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