Transient expression of progesterone receptor and cathepsin-l in human granulosa cells during the periovulatory period

García, Victor; Kohen, Paulina; Maldonado, Carola; Sierralta, Walter; Muñoz, Alex; Villarroel, Claudio; Strauss, Jerome F.; Devoto, Luigi

doi:10.1016/j.fertnstert.2011.12.039

Cited by 14 publications

(13 citation statements)

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“…A recent microarray analysis listed EGF-like factors ( AREG and EREG ) and PTG synthases ( PTGS2 and PTGES ) as differentially upregulated genes in granulosa cells isolated at 36 hours post-hCG compared with those obtained before hCG administration (20). There are only two reports showing PGR expression in granulosa cells of dominant follicles collected during the LH surge (21, 22). Therefore, more comprehensive study is needed to clarify exactly when and where these three key ovulatory mediators are induced and whether they cross regulate in periovulatory follicles.…”

mentioning

confidence: 99%

Coordinated Regulation Among Progesterone, Prostaglandins, and EGF-Like Factors in Human Ovulatory Follicles

Choi

Wilson

Hannon

et al. 2017

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context:In animal models, the luteinizing hormone surge increases progesterone (P4) and progesterone receptor (PGR), prostaglandins (PTGs), and epidermal growth factor (EGF)–like factors that play essential roles in ovulation. However, little is known about the expression, regulation, and function of these key ovulatory mediators in humans.Objective:To determine when and how these key ovulatory mediators are induced after the luteinizing hormone surge in human ovaries.Design and Participants:Timed periovulatory follicles were obtained from cycling women. Granulosa/lutein cells were collected from in vitro fertilization patients.Main Outcome Measures:The in vivo and in vitro expression of PGR, PTG synthases and transporters, and EGF-like factors were examined at the level of messenger RNA and protein. PGR binding to specific genes was assessed. P4 and PTGs in conditioned media were measured.Results:PGR, PTGS2, and AREG expressions dramatically increased in ovulatory follicles at 12 to 18 hours after human chorionic gonadotropin (hCG). In human granulosa/lutein cell cultures, hCG increased P4 and PTG production and the expression of PGR, specific PTG synthases and transporters, and EGF-like factors, mimicking in vivo expression patterns. Inhibitors for P4/PGR and EGF-signaling pathways reduced hCG-induced increases in PTG production and the expression of EGF-like factors. PGR bound to the PTGS2, PTGES, and SLCO2A1 genes.Conclusions:This report demonstrated the time-dependent induction of PGR, AREG, and PTGS2 in human periovulatory follicles. In vitro studies indicated that collaborative actions of P4/PGR and EGF signaling are required for hCG-induced increases in PTG production and potentiation of EGF signaling in human periovulatory granulosa cells.

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confidence: 99%

Coordinated Regulation Among Progesterone, Prostaglandins, and EGF-Like Factors in Human Ovulatory Follicles

Choi

Wilson

Hannon

et al. 2017

The Journal of Clinical Endocrinology &Amp; Metabolism

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“…Previous reports from our laboratory provided evidence of transient progesterone receptor expression in human granulosa cells during the peri-ovulatory period, disappearing after the LH surge (García et al, 2012). In addition, in-vitro studies on human granulosa cells showed that progesterone receptor mRNA expression significantly increases 6 h after HCG stimulation.…”

Section: Introductionmentioning

confidence: 61%

In-vitro study of gonadotrophin signaling pathways in human granulosa cells in relation to progesterone receptor expression

Henríquez

Kohen

Muñoz

et al. 2017

Reproductive BioMedicine Online

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In humans, data on gonadotrophin-activated (LH, HCG and FSH) progesterone receptor expression and signalling pathways involved in matrix metalloproteinases (MMPs) expression presumably linked to the follicle rupture, are limited. Our hypothesis is LH, HCG and FSH increase progesterone receptor expression in granulosa cells through different signalling pathways, leading to an increased expression of ADAMTS-1 and MMP3/10, which may mediate follicular rupture through the transcription factor, HIF1A. Human granulosa cells were isolated from follicular aspirates obtained from 22 healthy women participating in our IVF programme for male-factor infertility. Progesterone receptor and HIF1A expression was assessed by immunofluorescence, and PKA-PKC-PI3K- ERK1/2, ADAMTS-1 and MMP3/10 expression by Western blot in pre-ovulatory and in cultured granulosa cells. Results show that HCG, LH and FSH regulate progesterone receptor expression and activate PKA, PKC, PI3K and ERK1/2 signalling pathways in granulosa cells but progesterone receptor expression is only mediated by PKA, PKC and ERK pathways. HCG, FSH and LH regulated MMPs expression through progesterone receptors. Moreover, HCG-progesterone-receptor-dependent HIF1A expression stimulated MMP3/10 expression but not that of ADAMTS-1. These results suggest differential downstream progesterone receptor signalling, as progesterone receptor regulates MMP3/10 expression via HIF1A, which is not involved in ADAMTS-1 expression.

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“…In particular, AREG, EREG, and betacellulin bind to the epidermal growth factor receptor (EGFR) and induce the expression of genes involved in the cumulus expansion, oocyte maturation, and events associated with successful release of the oocytes and ovulation, [32][33][34][35] whereas PGR and its ligand are one of the key factors involved in the ovulatory process in humans. [36][37][38][39] Therefore, it appears that T-2 toxin can exert antiovulatory action through inhibition of the EGFR and PGR signaling networks.…”

Section: Discussionmentioning

confidence: 99%

T‐2 toxin downregulates LHCGR expression, steroidogenesis, and cAMP level in human cumulus granulosa cells

Pogrmić-Majkić

Nenadov

Stanić

et al. 2019

Environmental Toxicology

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Our goals were to investigate whether environmentally relevant doses of T‐2 toxin can affect human ovarian granulosa cells' function and to reveal the potential mechanism of T‐2 toxin's action. Results showed that T‐2 toxin strongly attenuated luteinizing hormone/choriogonadotropin receptor (LHCGR) mRNA expression in follicle‐stimulating hormone (FSH)‐stimulated human cumulus granulosa cells. Addition of human chorionic gonadotropin was not able to elicit maximal response of ovulatory genes amphiregulin, epiregulin, and progesterone receptor. T‐2 toxin reduced mRNA levels of CYP19A1 and steroidogenic acute regulatory protein (STAR) and lowered FSH‐stimulated estradiol and progesterone production. Mechanistic experiments demonstrated that T‐2 toxin decreased FSH‐stimulated cyclic adenosine monophosphate (cAMP) production. Addition of total PDE inhibitor 3‐isobutyl‐1‐methylxanthine prevented T‐2 toxin's action on LHCGR, STAR, and CYP19A1 mRNA expression in FSH‐stimulated human cumulus granulosa cells. Furthermore, T‐2 toxin partially decreased 8‐bromoadenosine 3′5′‐cyclic monophosphate (8‐Br‐cAMP)‐stimulated LHCGR and STAR, but did not affect 8‐Br‐cAMP‐stimulated CYP19A1 mRNA expression in human cumulus granulosa cells. Overall, our data indicate that environmentally relevant dose of T‐2 toxin decreases steroidogenesis and ovulatory potency in human cumulus granulosa cells probably through activation of PDE, thus posing a significant risk for female fertility.

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Transient expression of progesterone receptor and cathepsin-l in human granulosa cells during the periovulatory period

Cited by 14 publications

References 40 publications

Coordinated Regulation Among Progesterone, Prostaglandins, and EGF-Like Factors in Human Ovulatory Follicles

Coordinated Regulation Among Progesterone, Prostaglandins, and EGF-Like Factors in Human Ovulatory Follicles

In-vitro study of gonadotrophin signaling pathways in human granulosa cells in relation to progesterone receptor expression

T‐2 toxin downregulates LHCGR expression, steroidogenesis, and cAMP level in human cumulus granulosa cells

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