Semiquantitative RT-PCR analyses of total RNA document dramatic induction of each gene in COCs within 4 h after hCG, confirming microarray data that mRNA encoding these factors is present and induced in COCs of periovulatory follicles (37) and in situ hybridization data in rat periovulatory follicles 8 h after hCG (Ref. Thus, we hypothesized that LH induction of EGF-like factor expression in granulosa cells and cumulus cells might involve PGE2- and/or progesterone-mediated pathways. Terms and Conditions, 1999, 59: 4276-4284. Herein, we review the possible role of progestins and the progesterone receptor-associated signaling pathways in the development of breast cancer, as well as the therapeutic possibilities arising from our growing knowledge of the activation of the progesterone receptor by other proliferative mechanisms. In a nonengineered system, we have provided evidence of crosstalk between the PR and basic fibroblast growth factor using primary cultures of MPA-induced mammary carcinomas. Hormonal control of gene expression in the ovary. Molinolo AA, Lanari C, Charreau EH, Sanjuan N, Pasqualini CD: Mouse mammary tumors induced by medroxyprogesterone acetate: immunohistochemistry and hormonal receptors. Protein samples from whole ovaries or cultured granulosa cells were prepared either by homogenization in whole cell extract buffer (66) or boiling sodium dodecyl sulfate sample buffer (67) as indicated in the text and as described previously (67). 10.1073/pnas.97.7.3044. Recent Prog Horm Res. 10). Herein we document that epidermal growth factor (EGF)-like factors amphiregulin (Areg), epiregulin (Ereg), and betacellulin (Btc) are induced in cumulus oocyte complexes (COCs) by autocrine and paracrine mechanisms that involve the actions of prostaglandins (PGs) and progesterone receptor (PGR). The cells were infected with adenovirus expressing Myc-tagged PGRA or control andenovirus (Ref. As shown in Fig. PubMed Central Thus, PGR appears to exert a modulatory role in maintaining expression of these genes just before ovulation. Nagasawa H, Aoki M, Sakagami N, Ishida M: Medroxyprogesterone acetate enhances spontaneous mammary tumorigenesis and uterine adenomyosis in mice. Because cumulus cells have low or undetectable levels of LH receptor (27), other stimulatory factors appear to be required to induce expression of EGF-like factors in cumulus cells. Although acute regulation of the Areg gene requires an intact CRE region in the promoter of this gene (39, 40), the Areg promoter also contains an Sp1 element responsible for the basal transcription of this gene (39). Lastly, ovulated COCs were isolated from oviducts of mice 16 h after hCG and cultured for an additional 8 h without or with AREG to determine whether these factors remain critical for stability of expanded COCs after ovulation. Prostaglandin E2 stimulates the growth of colon cancer cells via induction of amphiregulin. The most potent inhibitor of FSH or AREG induction of Ptgs2 mRNA was PD98059, providing strong evidence that the MAPK/ERK1/2 pathway was activated by these agonists. Uterine Epithelial Estrogen Receptor- Controls Decidualization via a Paracrine Mechanism, Minireview: Complexity of Hematopoietic Stem Cell Regulation in the Bone Marrow Microenvironment, Minireview: Steroid-Regulated Paracrine Mechanisms Controlling Implantation. 1986, 77: 157-164. Interestingly, patients resistant to treatment with tamoxifen or high-dose progestins responded to antiprogestins. Although EGF-like factor mRNA was induced at 4 h in Ptgs2+/ mice, levels of Areg and Ereg but not Btc were reduced significantly at 4 h in Ptgs2/ mice. Epidermal growth factor family members: endogenous mediators of the ovulatory process.

Processing and localization of ADAMTS-1 and proteolytic cleavage of versican during cumulus matrix expansion and ovulation. COCs Collected from the Oviducts at 16 h Depend on AREG for Structural Integrity COCs were isolated from the oviducts of mice 16 h after hCG and cultured an additional 8 h in the presence or absence of AREG.

Breast Cancer Res Treat. Breast Cancer Res 4, 240 (2002). Statistical analyses were as described in Fig. As shown, the induction of Areg mRNA occurred more rapidly in response to forskolin than to AREG with significant increases occurring within 0.5 h. In contrast, increases in Ereg and Btc mRNA were not observed until 4 h with either agonist. 1, which is published as supplemental data on The Endocrine Societys Journals Online web site at http://mend.endojournals.org). We were able to demonstrate complete regression of experimental MPA-induced metastatic tumors with antiprogestins in vivo[27]. Animals were housed under a 16-h light/8-h dark schedule in the Center for Comparative Medicine at Baylor College of Medicine and provided food and water ad libitum. Induction of prostaglandin H synthase in rat preovulatory follicles by gonadotropin-releasing hormone. Lastly, induction of genes involved in steroidogenesis and steroid (progesterone) hormone action as well as those linked to immune cell function are regulated by AREG-dependent pathways, providing additional functional links between of these signaling cascades as well as potential novel functions for cumulus cells during the ovulation process. Ross RK, Paganini-Hill A, Wan PC, Pike MC: Effect of hormone replacement therapy on breast cancer risk: estrogen versus estrogen plus progestin. 5B). Estrogens drive the proliferation of the endometrium after menses, and induce progesterone receptor (PR) expression, whereas progesterone plays a role in proliferation, differentiation and maintenance of the endometrial epithelium and stroma in preparation for implantation. 20 and 33 and data not shown). These results show that COCs acquire steroidogenic capabilities and can produce progesterone. Jacobsen BM, Richer JK, Schittone SA, Horwitz KB: New human breast cancer cells to study progesterone receptor (PR) isoform ratio effects and ligand-independent gene regulation. Each pool represents RNA prepared from COCs of 12 mice. Blots were incubated primary antibody overnight at 4 C. After washing in TBST, enhanced chemiluminescence (ECL) detection was performed by using Pierce (Rockford, IL) Super Signal according the manufacturers specifications and appropriate exposure of the blots to Kodak x-ray film. To determine what cell signaling cascade(s) might mediate the induction of Ptgs2 mRNA, COCs were cultured with FSH or AREG in the absence or presence of inhibitors of putative downstream targets of FSH and EGFR signaling, namely protein kinase A, PKA (KT5720), p38MAPK/MAPK14 (SB203580), or MEK1 (PD98059) (Fig. MEM, DMEM:F12, and penicillin-streptomycin were from Invitrogen (Carlsbad, CA). COCs cells were isolated from these follicles by needle puncture and collected by pipette. More recently Park et al. 1). PubMed 2002, 288: 321-333. These results show that forskolin as well as FSH is a potent stimulator of Areg expression in COCs and that AREG is a potent inducer of the Ptgs2 gene, thereby indicating that induction of Ptgs2 mRNA by forskolin/FSH is mediated at least in part, by induction of Areg mRNA and subsequent AREG activation of the EGF receptor signaling. The LH surge initiates a remarkable reprogramming of granulosa cell and cumulus cell gene expression during the ovulatory cascade that impact cumulus expansion and oocyte maturation (37). Pazos P, Lanari C, Meiss R, Charreau EH, Pasqualini CD: Mammary carcinogenesis induced by I-methyl-I-nitrosourea (MNU) and medroxyprogesterone acetate (MPA) in BALB/c mice. Antibodies for AREG was purchased from R&D systems (Minneapolis, MN); phospho-p38MAPK, p38MAPK, and phospho-ERK1/2 were purchased from Cell Signaling Technologies (Danvers, MA). EMBO J. Hormone-regulated expression and localization of versican in the rodent ovary. B, COCs were cultured with PGE2 (500 ng/ml), AREG, AREG with AG or AREG with AG and PGE2 for 4 h. Statistical analyses were as described in Fig. 43 ; provided by V. Sriraman) overnight and were then stimulated with forskolin or PMA for 4 h, a regimen known to induce other genes (43). CAS Statistics were as described in the legend of Fig. However, earlier studies indicated that factors other than LH can induce cumulus expansion and oocyte maturation in culture, including prostaglandins (20) and epidermal growth factor (EGF) (28, 29). Briefly, cells were cultured in 12-well culture plates in 1% serum-containing medium (DMEM:F12 containing penicillin and streptomycin). All clinical trials have been carried out in patients with advanced disease, who had frequently become resistant to other endocrine therapies. Evidence of a direct PR activation by the protein kinase A pathway was provided by Edwards et al. The importance of progesterone in the ovulating follicle is evident by the infertility of the Pgr null mice (14). 10.1016/S0039-128X(00)00195-1. In clinical studies, from 169 patients treated, a complete response was observed in only one patient, and partial response rates varied between 11 and 56% [4]. In mice, progestins can act as co-carcinogens together with chemical initiators, such as N-methyl-N-nitrosourea [10] and dimethylbenzanthracene [11]. Furthermore, FSH-mediated induction of these genes in cultured COCs was dependent on EGF-R tyrosine kinase activity, p38MAPK, and ERK1/2 activity, but not on PTGS2 (37), indicating that genes in addition to Ptgs2 are targets of EGF receptor signaling in COCs. Developmental regulation of mitogen-activated protein kinase-activated kinases-2 and -3 (MAPKAPK-2/-3). 1999, 13: 829-836. THE SURGE OF LH induces marked functional (endocrine, biochemical, and molecular) changes in the preovulatory follicle. Transcriptional regulation of the epiregulin gene in the rat ovary. cDNA products were resolved on 5% polyacrylamide gels which were dried and exposed to film. Progesterone increases DNA synthesis in mouse mammary gland organ culture, decreases proliferation in primary cultures of normal human breast epithelium and cultured breast cancer cells, increases cell proliferation under certain experimental conditions in T47-D cells [14] and increases cell proliferation in primary cultures of experimental mouse mammary tumors [15]. https://doi.org/10.1186/bcr539. Google Scholar. Ovulated COCs were collected from the oviducts of mice at 16 and 24 h after hCG.

Induction of Ptgs2 mRNA and Areg mRNA Is Dependent on Activation of p38MAPK and ERK1/2 A, COCs were cultured with FSH or AREG as in Fig. The PR complex will bind a specific DNA sequence, the progesterone-responsive element, and will initiate the transcription of target genes. Endocr Rev. Vanzulli S, Efeyan A, Benavides F, Helguero L, Peters G, Shen J, Conti CJ, Lanari C, Molinolo A: p21, p27 and p53 in estrogen and antiprogestin-induced tumor regression of experimental mouse mammary ductal carcinomas. Part of Although, at this time AREG did not impact expression of immune cell-related (Pdcd1, Runx1, and Cd52) genes, it did exert a small but nonsignificant increase in matrix-related (Has2, Ptgs2, and Tnfaip6) genes. Ainsworth L, Tsang BK, Downey BR, Marcus GJ, Armstrong DT, Joyce IM, Pendola FL, OBrien M, Eppig JJ, Hizaki H, Segi E, Sugimoto Y, Hirose M, Saji T, Ushikubi F, Matsuoka T, Noda Y, Tanaka T, Yoshida N, Narumiya S, Ichikawa A, Kennedy CRJ, Zhang Y, Brandon S, Guan Y, Coffee K, Funk CD, Magnuson MA, Oates JA, Breyer M, Breyer RM, Davis BJ, Lennard DE, Lee CA, Tiano HF, Morham SG, Wetsel WC, Langenbach R, Matsumoto H, Ma WW, Smalley W, Trzakos JBR, Dey SK, Lydon JP, DeMayo F, Funk CR, Mani SK, Hughes AR, Montgomery CA, Shyamala G, Conneely OM, OMalley BW, Robker RL, Russell DL, Espey LL, Lydon JP, OMalley BW, Richards JS, Salustri A, Camaioni A, Di Giacomo M, Fulop C, Hascall VC, Richards JS, Russell DL, Ochsner S, Espey LL, Fulop C, Szanto S, Mukhopadhyay D, Bardox T, Kamath RV, Rugg MS, Day AJ, Salustri A, Hascall VC, Glant TT, Mikecz K, Ochsner SA, Day AJ, Breyer RM, Gomer RH, Richards JS, Camaioni A, Hascall VC, Yanagishita M, Salustri A, Russell DL, Ochsner SA, Hsieh M, Mulders S, Richards JS, Russell DL, Doyle KMH, Ochsner SA, Sandy JD, Richards JS, LeBaron RG, Zimmermann DR, Ruoslahti E, Shimada M, Nishibori N, Yamashita Y, Ito J, Mori T, Richards JS, Peng XR, Hseuh AJ, LaPolt PS, Bjersing L, Ny T, Sekiguchi T, Mizutani T, Yamada K, Kajitani T, Yazawa T, Yoshino M, Miyamoto K, Park J-Y, Su Y-Q, Ariga M, Law E, Jin S-LC, Conti M, Ashkenazi H, Cao X, Popliker M, Conti M, Tsafriri A, Hernandez-Gonzalez I, Gonzalez-Robayna IJ, Shimada M, Wayne CM, Ochsner SA, White L, Richards JS, Das SK, Chakraborty I, Paria BC, Wang XN, Plowman G, Dey SK, Shao J, Lee SB, Guo H, Evers BM, Sheng H, Brown CL, Meise KS, Plowman GD, Coffey RJ, Dempsey PJ, Sriraman V, Rudd MD, Lohmann SM, Mulders SM, Richards JS, Richards JS, Russell DL, Ochsner S, Hsieh M, Doyle KH, Falender AE, Lo YK, Sharma SC, Shao R, Markstrom E, Friberg PA, Johansson M, Billig H, Hedin L, Kurten DG, Kurten R, Richards JS, Gonzalez-Robayna IJ, Falender AE, Ochsner S, Firestone GL, Richards JS, Maizels ET, Cottom J, Jones JCR, Hunzicker-Dunn M, Maizels ET, Mukherjee A, Sithanandam G, Peters CA, Cottom J, Mayo KE, Hunzicker-Dunn M, Salvador LM, Maizels E, Hales DB, Miyamoto E, Yamamoto H, Hunzicker-Dunn M, Su YQ, Wigglesworth K, Pendola FL, OBrien MJ, Eppig JJ, Sekiguchi T, Mizutani T, Yamada K, Yazawa T, Kawata H, Yoshino M, Kajitani T, Kameda T, Minegishi T, Miyamoto K, Doyle KMH, Russell DL, Sriraman V, Richards JS, Owen GL, Richer JK, Tung L, Takimoto G, Horwitz KB, Orly J, Rei Z, Greenberg N, Richards JS, Richards JS, Hernandez-Gonzalez I, Gonzalez-Robayna I, Teuling E, Lo Y, Boerboom D, Falender AE, Doyle KH, LeBaron R, Thompson V, Sandy JD, Gonzalez-Robayna IJ, Alliston TN, Buse P, Firestone GL, Richards JS, Oxford University Press is a department of the University of Oxford. Additionally, both FSH and AREG induced Areg and Ereg expression within 4 h in cultured COCs, actions that were completely suppressed by the PTGS2 selective inhibitor, NS398, suggesting that PGs mediate the effects of these agonists on EGF-like factor expression. Specific bands were quantified by densitometric analyses using a Molecular Dynamics Personal Densitometer. Progesterone regulates transcription of the p21 (WAF1) cyclin-dependent kinase inhibitor gene through Sp1 and CBP/p300. Estrogen concentrations decline in follicular fluid as a consequence of the reduced expression of aromatase (Cyp19a1) and Hsd171 (Hsd17b1) in granulosa and theca cells, respectively. McKenna NJ, Lanz RB, O'Malley BW: Nuclear receptor coregulators: cellular and molecular biology. AREG Induces the Expression of Genes Involved in Matrix Formation, Steroidogenesis, and Immune Cell Function in COCs COCs were cultured with AREG without or with AG to block EGF receptor activity for 4 h (upper panels) or 16 h (lower panels). Release of a predominant N-glycosylated 43-kDa soluble form. Purification and characterization of a novel, distinct isoform of prostaglandin endoperoxide synthase induced by human chorionic gonadotropin in granulosa cells of rat preovulatory follicles. EGF-like growth factors as mediators of LH action in the ovulatory follicle.

In vivo demonstration of these mechanisms will strengthen the role of the PR on mammary gland or breast cancer proliferation. As expected, AREG induced Ptgs2, Has2, and Tnfaip6 expression in cultured COCs at 4 h. In addition, genes involved in steroidogenesis Star and Cyp11a1 were induced by AREG alone, a process reduced by the EGF receptor tyrosine kinase blocker AG (Fig. Mol Carcinog. EP2 and EP4 prostanoid receptor signaling. **, P < 0.01; ***, P < 0.05. 1. Radiolabeled [32P]deoxy (d)-CTP was purchased from ICN (Los Angeles, CA). Rather, PGRA-Myc enhanced significantly the effect of PMA on EGF factor (Areg and Ereg) induction. The other sites (Ser 102, Ser 294 and Ser 345) are hormone inducible, and 12 hours of treatment are required to reach maximal phosphorylation. Moreover, PGE2 reversed the inhibition of AG on AREG-mediated induction of Areg and Has2 mRNA but not that of Ptgs2, clearly placing induction of Ptgs2 mRNA downstream of EGFR activation.

These coregulatory proteins may modulate histone acetylation/deacetylation and chromatin remodeling, and may have additional effects [18]. Acute signaling by the LH receptor is independent of protein kinase C activation. CAS Bardon S, Vignon F, Montcourrier P, Rochefort H: Steroid receptor-mediated cytotoxicity of an antiestrogen and an antiprogestin in breast cancer cells. However, AREG was more potent than forskolin in stimulating rapid ERK1/2 phosphorylation. Sequential effects of follicle-stimulating hormone and luteinizing hormone on mouse cumulus expansion in vitro. In addition the PGE2 receptor subtype (Ptger2; EP2) and progesterone receptor (Pgr; Nr3c3; PR) are induced in granulosa cells of preovulatory (PO) follicles by LH (710). 2002, 277: 27793-27800. Decreased expression of tumor necrosis factor-a-stimulated gene 6 in cumulus cells of the cyclooxygenase-2 and EP2 null mice. Oligonucleotide primers for RT-PCRs were from Sigma-Genosys (Houston, TX). Briefly, total RNA was reverse transcribed using 500 ng poly-deoxythymidine (Amersham Pharmacia Biotech) and 0.25 U avian myeloblastosis virus-reverse transcriptase (Promega Corp., Madison, WI) at 42 C for 75 min and 95 C for 5 min. 10.1210/me.13.6.829. 1967, 156: 1050-1054. 1. Nonexpanded COCs were selected and then were cultured in separate wells of a Falcon 24-well plate (Becton Dickinson, Franklin Lakes, NJ) in 1.0 ml of defined medium (20) containing 1% fetal bovine serum without or with FSH (100 ng/ml), Amphiregulin (250 ng/ml), PGE2 (500 ng/ml) and various protein kinase inhibitors: PKA (KT5720), MEK1 (PD98059), p38MAPK (SB203580) and EGFR activation via tyrosine phosphorylation (AG) as well as a selective inhibitor of PTGS2 (NS398).

4B). 2022 BioMed Central Ltd unless otherwise stated. J Natl Cancer Inst. An immunoreactive band at approximately 60 kDa corresponds to the cellular, nonprocessed form of AREG, whereas the smaller product may be a soluble form (41). 1996, 17: 126-133. Another gene rapidly induced by LH is Prg. 1999, 70: 133-142. Maller JL: The elusive progesterone receptor in Xenopus oocytes. Gene expression profiles of cumulus cell oocyte complexes during ovulation reveal cumulus cells express neuronal and immune-related genes: does this expand their role in the ovulation process? Most of the tumors were lobular in morphology and they progressively ceased to express receptors after a few in vivo passages. statement and Cookies policy. 7C). Because the promoters of the Areg and Ereg genes can be transactivated by cAMP-dependent mechanisms (39, 45) and because one target of LH and is Ptgs2, we hypothesized that prostaglandins, specifically PGE2 (46) might be produced locally and via the EP2 receptor PTGER2 (7) serve as the intermediary stimulus. Anovulation in cyclo-oxygenase-2-deficient mice is restored by prostaglandin E2 and interleukin-1b. Two separate pools of RNA were analyzed by semiquantiative RT-PCR using specific primers as shown in Table 1. Masayuki Shimada, Inmaculada Hernandez-Gonzalez, Ignacio Gonzalez-Robayna, JoAnne S. Richards, Paracrine and Autocrine Regulation of Epidermal Growth Factor-Like Factors in Cumulus Oocyte Complexes and Granulosa Cells: Key Roles for Prostaglandin Synthase 2 and Progesterone Receptor, Molecular Endocrinology, Volume 20, Issue 6, 1 June 2006, Pages 13521365, https://doi.org/10.1210/me.2005-0504. Extracts (30 g protein) were resolved by SDS-PAGE (8 or 10%) and transferred to Immobilon-P nylon membranes (Millipore Corp, Bedford, MA). 2000, 14: 52-65. Mol Endocrinol. Localization of luteinizing hormone receptor messenger ribonucleic acid expression in ovarian cell lysates during follicular development and ovulation. Recent microarray data indicated that many genes in addition to Ptgs2, Has2, and Tnaip6 were induced in COCs in vivo at 8 h after hCG (37). In support of this notion, we document that Areg and Ereg but not Btc expression levels were markedly reduced in COCs and granulosa cells of Ptgs2 null mice. Coordinate transactivation of the ADAMTS-1 gene by luteinizing hormone and progesterone receptor.

Conversely, AREG but not FSH induced Ptsg2 mRNA at 0.5 h with peak expression of Ptgs2 and Areg mRNAs at 4 h, processes blocked by the EGF receptor tyrosine kinase inhibitor AG1478 (AG), PD98059, and NS398. COCs were scored for morphological appearance and used for the isolation of total RNA. PubMed Induction of Areg, Ereg, and Btc mRNA by either FSH or AREG at 4 h was blocked by AG, an inhibitor of EGF receptor tyrosine kinase activity (Fig. Carcinogenesis. Disrupted function of tumor necrosis stimulated gene 6 blocks cumulus cell-oocyte complex function. Digital images were captured using an Axiphot microscope with 540 objectives. However, in ovulated COCs, AREG may regulate the expression of other genes. The classic view (namely, estrogens = proliferation and progestins = differentiation) has been extrapolated to systems other than the endometrium, such as the mammary gland, and has probably contributed to a long-held belief that estrogens are the main steroid hormones implicated in the induction of breast cancer. Other genes regulated by PGR in granulosa cells, such as cyclic-dependent protein kinase II (cGKII, Prkg2) (43) and cathpsinL [Ctsl; (60)] have at least one Sp1/Sp3 site. 3A, Areg, Ereg, and Btc mRNA was induced markedly in COCs and granulosa cells of Ptgs2+/ mice at 4 h. In contrast, induction of mRNA encoding Areg and Ereg mRNA but not that encoding Btc was impaired significantly in COCs and granulosa cells of the Ptgs2/ mice at this time interval. Laboratory of Hormonal Carcinogenesis, Instituto de Biologa y Medicina Experimental, Consejo Nacional de Investigaciones Cientficas y Tcnicas, Vuelta de Obligado 2490, Buenos Aires, C1428ADN, Argentina, You can also search for this author in Richer JK, Jacobsen BM, Manning NG, Abel MG, Wolf DM, Horwitz KB: Differential gene regulation by the two progesterone receptor isoforms in human breast cancer cells. Lanari, C., Molinolo, A.A. Progesterone receptors - animal models and cell signaling in breast cancer Diverse activation pathways for the progesterone receptor - possible implications for breast biology and cancer. Gestyl (eCG) was purchased from Professional Compounding Center of America (Houston, TX). All PCRs contained [32P]dCTP (ICN, Los Angeles, CA), Taq Polymerase and Thermocycle buffer (Promega Corp.) as in previous studies (64, 65). PGE2 was from Sigma (St. Louis, MO). Estrogens have traditionally been considered associated with an increased risk of breast cancer. Prostaglandin E2 synergistically enhances receptor tyrosine kinase-dependent signaling in colon cancer. Expression of epiregulin and amphiregulin in the rat ovary. Granulosa cells were infected with adenovirus expressing PGR-A or LacZ and cultured overnight. Cyclic guanosine 5-monophosphate-dependent protein kinase II is induced by luteinizing hormone and progesterone receptor-dependent mechanisms in granulosa cells and cumulus oocyte complexes of ovulating follicles. J Natl Cancer Inst. Activated PRs would recruit a series of important regulatory proteins, which can serve as coactivators or corepressors, such as SRC-1, SRC-2 and SRC-3, CBP/p300 and others. 10.1096/fj.00-0165com. 4 with or without inhibitors of PKA (KT; KT5720, 10 m), p38MAPK (SB203580, 20 m) or MEK1 (PD; PD98059, 20 m). They thank Dr I. Lthy and Dr H. Coirini for discussion, and Dr C. D. Pasqualini for revising the manuscript. When induction of Ptgs2 mRNA was analyzed in these same samples, a significant response to AREG but not to forskolin occurred at 0.5 and 1 h, whereas by 4 h the induction by AREG and forskolin was similar (Fig. CAS Female mice null for Pgr (PRKO) fail to ovulate, even in response to exogenous hormones (13, 14). LH induces EGF like factor expression in granulosa cells (33), most probably via the p38MAPK pathway (52, 53). California Privacy Statement,

Transient expression of progesterone receptor messenger RNA in ovarian granulosa cells after the preovulatory luteinizing hormone surge. 2002, 23: 749-757. Article However, when the morphology of COCs was examined, those cultured with AREG for 1624 h appeared similar to COCs isolated from the oviducts at 24 h, whereas COCs cultured in the absence of AREG had begun to disintegrate. The approximately 60-kDa band noted in the Western blot represents nonprocessed cellular AREG and was quantified by densitometric analyses using a Molecular Dynamics Personal Densitometer (A). This indicates that fibroblast growth factors, which act by activation of MAPK, may also use the PR pathway to induce cell proliferation. By the PGE/PTGER2 pathway, Areg and Ereg mRNA can be induced in cumulus cells independently of granulosa cells leading to EGFR activation (6 ) and induction of Ptgs2 and PG production (7 ) by autocrine mechanisms. No tumors were observed in untreated controls or in virgin female BALB/c mice of our colony. Furthermore, induction of Areg and Ereg mRNA by FSH or AREG was blocked by the PTGS2 inhibitor NS398. Google Scholar. The molecular bridges that link the LH surge with functional changes in cumulus cells that possess few LH receptors are being unraveled. Ovarian epidermal growth factor-like activity. Note that forskolin mediated more rapid induction of Areg mRNA (0.5 h) than does AREG, whereas AREG induced expression of Ptgs2 mRNA more rapidly (0.5 h) than forskolin. Follicle stimulating hormone (FSH) activates the p38 mitogen-activated protein kinase pathway, inducing small heat shock protein phosphorylation and cell rounding in immature rat ovarian granulosa cells. We demonstrated in 1986 [5] that, in BALB/c female mice, medroxyprogesterone acetate (MPA) alone induces mammary carcinomas that expresses PRs and ERs, that are hormone dependent and that, unlike what happens in most other experimental models of breast cancer, originate axillary and lung metastases [6, 7]. Their physiological roles are different according to their structural and functional properties. As shown, forskolin stimulated Areg, Ereg, and Btc mRNA, whereas PMA was ineffective (Fig. In a similar manner, when mouse granulosa cells were coinfected/transfected with adenoviral PGRA and a Snap-25 promoter luciferase-reported construct, PMA enhanced promoter activity through Sp1/Sp3 binding sites (our unpublished data). Mean sd were calculated and analyzed by one-way ANOVA and Neuman-Keuls Multiple Comparison (GraphPad Prism). Copyright 2006 by The Endocrine Society, Editorial: Final Musings on the Impact of Molecular Endocrinology, Editorial: Reflections on the Impact of Molecular Endocrinology on a Scientific Career, The Journal of Clinical Endocrinology & Metabolism, Receive exclusive offers and updates from Oxford Academic. After 4 or 16 h, the COCs total RNA was extracted (see below).