Céline C. M. Väänänen

Bio: Céline C. M. Väänänen is an academic researcher from University of British Columbia. The author has contributed to research in topics: Prostaglandin & Human chorionic gonadotropin. The author has an hindex of 3, co-authored 3 publications receiving 16 citations.

Regulation of prostaglandin F2alpha-receptor mRNA in human granulosa-luteal cells by human chorionic gonadotrophin and prostaglandin F2alpha.

Abstract: This study examined the effects of prostaglandin F2α (PGF2α) and human chorionic gonadotropin (hCG) on the levels of PGF2α-receptor (PGF2α-R) mRNA and steroidogenesis, in the human granulosa luteal cell (hGLC). Human GLCs collected from patients undergoing in vitro fertilization, were cultured for 24 h, after which cells were exposed to culture media containing either vehicle, hCG (1 IU/mL), or hCG plus PGF2α (10−11–10−6 M), for a further 24 h. Following the treatment period, media were collected and stored (−20°C) until assayed for progesterone and 17β-estradiol (estradiol). Immediately following the treatment period, cells were extracted for total RNA. Transcripts for PGF2α-R were detected by PCR with two different sets of oligonucleotide primers based on the published human and rat PGF2α-R sequences. PCR products were confirmed to be those of PGF2α-R by size and by Southern blot hybridization with an internal oligo nucleotide probe. All experiments were performed a minimum of three times, on cells from a minimum of three separate patients. Prostaglandin F2α-R mRNA was significantly downregulated, whereas progesterone and estradiol production were significantly stimulated by hCG. Conversely, both low (10−11 M) and high concentrations (10−6 M) of PGF2α restored PGF2α-R mRNA levels to those of the controls, whereas steroidogenesis was significantly inhibited by these conditions. At a concentration of 10−9 M PGF2α-R mRNA was barely detectable. Progesterone and estradiol production were inversely related to PGF2α-R levels, since hCG-stimulated progesterone and estradiol production were completely restored in the presence of 10−9 M PGF2α. Messenger RNA levels for the housekeeping gene β-actin were unaltered by the above treatments. In conclusion, in the human granulosa luteal cell, PGF2α-R mRNA levels are inversely related to hCG-stimulated steroidogenesis (which was biphasic in nature). Moreover, in the presence of hCG, PGF2α downregulates its receptor mRNA, thus providing a potential form of negative feedback on its own actions, which may be important in rescuing the corpus luteum from PGF2α-mediated luteolysis should pregnancy occur.

Stepwise activation of the gonadotropic signal transduction pathway, and the ability of prostaglandin F2α to inhibit this activated pathwayto inhibit this activated pathway

Abstract: Through selective activation of the gonadotropic signal transduction pathway, we have determined the probable site of the antigonadotropic effects of prostaglandin F2α (PGF2α) in the human granulosa-luteal cell (hGLC). The gonadotropic signal transduction pathway was activated at the level of the receptor (luteinizing hormone and β-adrenergic), stimulatory G protein (Gs), adenylate cyclase (AC), and protein kinase A (PKA) by human chorionic gonadotropin (hCG) and isoproterenol (Iso), cholera toxin (CTX), forskolin, and dibutryl cAMP (Db cAMP), respectively. Concomitantly, the ability of PGF2α to inhibit progesterone production in response to the activation of this cascade at these different levels was examined. hGLCs were obtained from in vitro fertilization patients and were precultured for 8 d in Medium 199 supplemented with fetal bovine serum (M199; 10% FBS). Following the preculture period, cells were treated with either vehicle or one of the above activators of the gonadotropic pathway, either in the absence or presence of PGF2α (in M199; No FBS). Following the treatment period, media were collected and assayed for progesterone by RIA. Prostaglandin F2α (10−6 M) significantly inhibited hCG (1 IU/mL), Iso (10−5 M), CTX (1 µg/mL), and forskolin- (10−5 M) stimulated progesterone production. Conversely, PGF2α did not inhibit progesterone production stimulated by a saturating concentration of Db cAMP (10−6 M). The ability of PGF2α to inhibit hCG- or CTX-stimulated progesterone production was attenuated by pertussis toxin (PTX; 50 ng/mL). In conclusion, through a pertussis toxinsensitive G protein, PGF2α inhibits progesterone production at a level below AC, and above the activation of PKA by cAMP.

Interaction of Prostaglandin F2α and Prostaglandin-E2 on Progesterone Production in Human Granulosa-Luteal Cells

Abstract: This study examined the effects of prostaglandin-F2α (PGF2α), prostaglandin-E2 (PGE2) and their interactions on progesterone production in human granulosa-l

International Union of Basic and Clinical Pharmacology. LXXXIII: Classification of Prostanoid Receptors, Updating 15 Years of Progress

Abstract: It is now more than 15 years since the molecular structures of the major prostanoid receptors were elucidated. Since then, substantial progress has been achieved with respect to distribution and function, signal transduction mechanisms, and the design of agonists and antagonists ( ). This review systematically details these advances. More recent developments in prostanoid receptor research are included. The DP2 receptor, also termed CRTH2, has little structural resemblance to DP1 and other receptors described in the original prostanoid receptor classification. DP2 receptors are more closely related to chemoattractant receptors. Prostanoid receptors have also been found to heterodimerize with other prostanoid receptor subtypes and nonprostanoids. This may extend signal transduction pathways and create new ligand recognition sites: prostacyclin/thromboxane A2 heterodimeric receptors for 8- epi -prostaglandin E2, wild-type/alternative (alt4) heterodimers for the prostaglandin FP receptor for bimatoprost and the prostamides. It is anticipated that the 15 years of research progress described herein will lead to novel therapeutic entities.

Differential role of PR-A and -B isoforms in transcription regulation of human GnRH receptor gene.

Abstract: The presence of progesterone response element (PRE) in the 5′-flanking region of the human GnRH receptor (GnRHR) suggests the possible regulation of this gene by progesterone (P). In the present study, we examined the effects of P in transcriptional regulation of human GnRHR gene expression at the pituitary and placenta levels since the GnRHR has been detected in both tissues. By the use of transient transfection assays, a differential regulation of human GnRHR promoter activity by P was observed. P treatment resulted in a decrease in promoter activity in the pituitary αT3–1 cells, suggesting a P-mediated inhibitory action. Interestingly, P is found to have a stimulatory role at the placental expression of this gene. Addition of RU486 to, or inhibition of endogenous P production by, the placental JEG-3 cells leads to a decrease in promoter activity, which is reversed by the replacement of P. Further studies have identified a putative PRE, namely human GR-PRE (located between −535 and− 521, related to tran...

Prostaglandin E2 concentrations in gingival crevicular fluid: observations in untreated chronic periodontitis

Abstract: Objectives: We set out to monitor gingival crevicular fluid prostaglandin E2 (GCF-PGE2) concentrations longitudinally in a cohort of subjects with chronic periodontitis, given that we had noted an unexplained trend for GCF-PGE2 concentrations to gradually increase in control groups and placebo populations in previously published clinical trials. Material and Methods: 41 adults with moderate-severe chronic periodontitis were recruited. GCF samples were collected from 8 test sites (with 5–8 mm probing depths and attachment loss) every 30 days for 150 days, and assayed for PGE2. Clinical measurements (probing depths, attachment levels, bleeding on probing) were recorded at days 0 and 150. Results: A gradual and statistically significant increase in GCF-PGE2 concentrations was observed over the course of the study, from 40.3 ng/ml to 83.1 ng/ml (p 0.05). Over the same time period, no statistically significant changes in clinical parameters were recorded, with the exception of mean probing depths, which decreased slightly from 5.73 mm to 5.51 mm (p<0.05). Conclusion: A trend for gradually increasing GCF-PGE2 concentrations in the absence of any clinical signs of disease progression was noted in a group of patients monitored longitudinally. We suggest that this phenomenon is to be expected in longitudinal clinical trials, and propose a new model for the role of PGE2 in the pathogenesis of periodontal destruction. We feel that if GCF mediators are to be monitored in clinical studies, then both concentrations and absolute mediator content should be calculated, and a standardised sampling protocol should be employed.

Effects of Nicotine on Human Luteal Cells In Vitro: A Possible Role on Reproductive Outcome for Smoking Women

Abstract: We investigated the effect of nicotine and its methylated metabolite, N-methyl-nicotine (M-nicotine), on human luteal cells by measuring release of progesterone and prostaglandins (PGs) from cultured cells and by testing gene expression of vascular endothelial growth factor (VEGF), an angiogenic factor strictly involved in luteal pathophysiology. Primary cultures of human luteal cells were treated for 24 h with nicotine and M-nicotine (from 10−6 to 10−11 M) either alone or combined with hCG (25 ng/ml); progesterone and PGs were assayed in the culture medium. In another group of experiments, luteal cells were treated for 24 h with nicotine and M-nicotine (10−7 M) to perform reverse transcriptase-polymerase chain reaction on VEGF mRNA. Nicotine and M-nicotine negatively affected basal luteal steroidogenesis at all tested concentrations, but neither was able to affect hCG-induced progesterone release. Both substances were able to significantly increase PGF2α release from luteal cells, with a dose-re...

Ovarian reserve status in young women is associated with altered gene expression in membrana granulosa cells

Abstract: Diminished ovarian reserve (DOR) is a challenging diagnosis of infertility, as there are currently no tests to predict who may become affected with this condition, or at what age. We designed the present study to compare the gene expression profile of membrana granulosa cells from young women affected with DOR with those from egg donors of similar age and to determine if distinct genetic patterns could be identified to provide insight into the etiology of DOR. Young women with DOR were identified based on FSH level in conjunction with poor follicular development during an IVF cycle (n = 13). Egg donors with normal ovarian reserve (NOR) comprised the control group (n = 13). Granulosa cells were collected following retrieval, RNA was extracted and microarray analysis was conducted to evaluate genetic differences between the groups. Confirmatory studies were undertaken with quantitative RT-PCR (qRT-PCR). Multiple significant differences in gene expression were observed between the DOR patients and egg donors. Two genes linked with ovarian function, anti-Mullerian hormone (AMH) and luteinizing hormone receptor (LHCGR), were further analyzed with qRT-PCR in all patients. The average expression of AMH was significantly higher in egg donors (adjusted P-value = 0.01), and the average expression of LHCGR was significantly higher in DOR patients (adjusted P-value = 0.005). Expression levels for four additional genes, progesterone receptor membrane component 2 (PGRMC2), prostaglandin E receptor 3 (subtype EP3) (PTGER3), steroidogenic acute regulatory protein (StAR), and StAR-related lipid transfer domain containing 4 (StarD4), were validated in a group consisting of five NOR and five DOR patients. We conclude that gene expression analysis has substantial potential to determine which young women may be affected with DOR. More importantly, our analysis suggests that DOR patients fall into two distinct subgroups based on gene expression profiles, indicating that different mechanisms may be involved during development of this pathology.