Rosiglitazone increases expression of steroidogenic acute regulatory protein and progesterone production through PPARγ–EGFR–ERK1/2 in human cumulus granulosa cells
Kristina Pogrmic-Majkic A E , Gordana Kosanin A , Dragana Samardzija Nenadov A , Svetlana Fa A , Bojana Stanic B , Aleksandra Trninic Pjevic C D and Nebojsa Andric A E
+ Author Affiliations
- Author Affiliations
A University of Novi Sad, Faculty of Sciences, Department of Biology and Ecology, D. Obradovica Sq. 2, 21000 Novi Sad, Serbia.
B University of Novi Sad, Faculty of Technical Sciences, Department of Environmental Engineering and Occupational Safety and Health, D. Obradovica Sq. 6, 21000 Novi Sad, Serbia.
C University of Novi Sad, Faculty of Medicine, Hajduk Veljkova 3, 21000 Novi Sad, Serbia.
D Clinic for Gynecology and Obstetrics, Clinical Center of Vojvodina, Branimira Cosica 7, 21000 Novi Sad, Serbia.
E Corresponding authors. Emails: kristina.pogrmic@dbe.uns.ac.rs; nebojsa.andric@dbe.uns.ac.rs
Reproduction, Fertility and Development 31(11) 1647-1656 https://doi.org/10.1071/RD19108
Submitted: 25 December 2018 Accepted: 22 May 2019 Published: 25 June 2019
Abstract
The mechanism by which rosiglitazone (ROSI: a thiazolidinedione (TZD)) affects steroid production in undifferentiated human granulosa cells is not known. In this study, cultured human cumulus granulosa cells were exposed to ROSI and pharmacological inhibitors of the extracellular signal-regulated kinase 1/2 (ERK1/2), epidermal growth factor receptor (EGFR) and peroxisome proliferator-activated receptor gamma (PPARγ) signalling pathways. Expression of progesterone biosynthetic enzymes, PPARγ and PPARα, progesterone production and ERK1/2 activation were analysed. After 48 h, 30 μM ROSI increased STAR, 3βHSD and PPARγ mRNA and elevated progesterone production in human cumulus granulosa cells. Addition of ERK1/2 (U0126), EGFR (AG1478) and PPARγ (GW9662) inhibitors prevented the ROSI-induced STAR mRNA expression and progesterone production after 48 h. Inhibition of PPARγ, but not EGFR or ERK1/2, decreased the PPARγ mRNA levels induced by ROSI in human cumulus granulosa cells after 48 h. On the other hand, U0126 and GW9662 prevented the ROSI-induced increase in PPARγ transcripts after 6 h. Western blot analysis showed that ROSI induced a rapid ERK1/2 activation, which was prevented by inhibition of ERK1/2, EGFR and PPARγ in human cumulus granulosa cells. Overall, these data suggested that PPARγ, EGFR and ERK1/2 were involved in the stimulatory effect of ROSI on STAR expression and progesterone production in undifferentiated human cumulus granulosa cells.
Additional keywords: 3βHSD, CYP11A1, PPARα, STAR, undifferentiated human granulosa cells.
References
Andric, N., and Ascoli, M. (2006). A delayed gonadotropin-dependent and growth factor-mediated activation of the extracellular signal-regulated kinase 1/2 cascade negatively regulates aromatase expression in granulosa cells. Mol. Endocrinol. 20, 3308–3320.| A delayed gonadotropin-dependent and growth factor-mediated activation of the extracellular signal-regulated kinase 1/2 cascade negatively regulates aromatase expression in granulosa cells.Crossref | GoogleScholarGoogle Scholar | 16973759PubMed |
Andric, N., and Ascoli, M. (2008). The luteinizing hormone receptor-activated extracellularly regulated kinase-1/2 cascade stimulates epiregulin release from granulosa cells. Endocrinology 149, 5549–5556.
| The luteinizing hormone receptor-activated extracellularly regulated kinase-1/2 cascade stimulates epiregulin release from granulosa cells.Crossref | GoogleScholarGoogle Scholar | 18653716PubMed |
Araki, T., Varadinova, M., Goldman, M., Rosenwaks, Z., Poretsky, L., and Seto-Young, D. (2011). Rosiglitazone and pioglitazone alter aromatase kinetic properties in human granulosa cells. PPAR Res. 2011, 926438.
| Rosiglitazone and pioglitazone alter aromatase kinetic properties in human granulosa cells.Crossref | GoogleScholarGoogle Scholar | 22220166PubMed |
Baumgarten, S. C., Convissar, S. M., Fierro, M. A., Winston, N. J., Scoccia, B., and Stocco, C. (2014). IGF1R signaling is necessary for FSH-induced activation of AKT and differentiation of human cumulus granulosa cells. J. Clin. Endocrinol. Metab. 99, 2995–3004.
| IGF1R signaling is necessary for FSH-induced activation of AKT and differentiation of human cumulus granulosa cells.Crossref | GoogleScholarGoogle Scholar | 24848710PubMed |
Baumgarten, S. C., Convissar, S. M., Zamah, A. M., Fierro, M. A., Winston, N. J., Scoccia, B., and Stocco, C. (2015). FSH regulates IGF2 expression in human granulosa cells in an AKT-dependent manner. J. Clin. Endocrinol. Metab. 100, E1046–E1055.
| FSH regulates IGF2 expression in human granulosa cells in an AKT-dependent manner.Crossref | GoogleScholarGoogle Scholar | 26066673PubMed |
Burgermeister, E., and Seger, R. (2008). PPARγ and MEK interactions in cancer. PPAR Res. 2008, 309469.
| PPARγ and MEK interactions in cancer.Crossref | GoogleScholarGoogle Scholar | 18596912PubMed |
Chan, L. Y. S., Yeung, J. H. K., and Lau, T. K. (2005). Placental transfer of rosiglitazone in the first trimester of human pregnancy. Fertil. Steril. 83, 955–958.
| Placental transfer of rosiglitazone in the first trimester of human pregnancy.Crossref | GoogleScholarGoogle Scholar |
Chen, Q., Sun, X., Chen, J., Cheng, L., Wang, J., Wang, Y., and Sun, Z. (2009). Direct rosiglitazone action on steroidogenesis and proinflammatory factor production in human granulosa-lutein cells. Reprod. Biol. Endocrinol. 7, 147.
| Direct rosiglitazone action on steroidogenesis and proinflammatory factor production in human granulosa-lutein cells.Crossref | GoogleScholarGoogle Scholar | 20003221PubMed |
Chen, L., Zhou, Z., Shen, M., and Ma, A. (2011). Simultaneous determination and pharmacokinetic study of metformin and rosiglitazone in human plasma by HPLC-ESI-MS. J. Chromatogr. Sci. 49, 94–100.
| Simultaneous determination and pharmacokinetic study of metformin and rosiglitazone in human plasma by HPLC-ESI-MS.Crossref | GoogleScholarGoogle Scholar | 21223632PubMed |
El-Enany, N. M., Abdelal, A. A., Belal, F. F., Itoh, Y. I., and Nakamura, M. N. (2012). Development and validation of a rephrased phase-HPLC method for simultaneous determination of rosiglitazone and glimepiride in combined dosage forms and human plasma. Chem. Cent. J. 6, 9.
| Development and validation of a rephrased phase-HPLC method for simultaneous determination of rosiglitazone and glimepiride in combined dosage forms and human plasma.Crossref | GoogleScholarGoogle Scholar | 22277722PubMed |
Ernst, J., Jann, J.-C., Biemann, R., Koch, H. M., and Fischer, B. (2014). Effects of the environmental contaminants DEHP and TCDD on estradiol synthesis and aryl hydrocarbon receptor and peroxisome proliferator-activated receptor signalling in the human granulosa cell line KGN. Mol. Hum. Reprod. 20, 919–928.
| Effects of the environmental contaminants DEHP and TCDD on estradiol synthesis and aryl hydrocarbon receptor and peroxisome proliferator-activated receptor signalling in the human granulosa cell line KGN.Crossref | GoogleScholarGoogle Scholar | 24950685PubMed |
Fan, W., Yanase, T., Morinaga, H., Mu, Y.-M., Nomura, M., Okabe, T., Goto, K., Harada, N., and Nawata, H. (2005). Activation of peroxisome proliferator-activated receptor-γ and retinoid X receptor inhibits aromatase transcription via nuclear factor-κB. Endocrinology 146, 85–92.
| Activation of peroxisome proliferator-activated receptor-γ and retinoid X receptor inhibits aromatase transcription via nuclear factor-κB.Crossref | GoogleScholarGoogle Scholar | 15459115PubMed |
Fan, H.-Y., Liu, Z., Johnson, P. F., and Richards, J. S. (2011). CCAAT/enhancer-binding proteins (C/EBP)-α and -β are essential for ovulation, luteinization, and the expression of key target genes. Mol. Endocrinol. 25, 253–268.
| CCAAT/enhancer-binding proteins (C/EBP)-α and -β are essential for ovulation, luteinization, and the expression of key target genes.Crossref | GoogleScholarGoogle Scholar | 21177758PubMed |
Fang, L., Cheng, J. C., Chang, H. M., Sun, Y. P., and Leung, P. C. K. (2013). EGF-like growth factors induce COX-2-derived PGE2 production through ERK1/2 in human granulosa cells. J. Clin. Endocrinol. Metab. 98, 4932–4941.
| EGF-like growth factors induce COX-2-derived PGE2 production through ERK1/2 in human granulosa cells.Crossref | GoogleScholarGoogle Scholar | 24092824PubMed |
Froment, P., Gizard, F., Defever, D., Staels, B., Dupont, J., and Monget, P. (2006). Peroxisome proliferator-activated receptors in reproductive tissues: From gametogenesis to parturition. J. Endocrinol. 189, 199–209.
| Peroxisome proliferator-activated receptors in reproductive tissues: From gametogenesis to parturition.Crossref | GoogleScholarGoogle Scholar | 16648288PubMed |
Gardner, O. S., Dewar, B. J., Earp, H. S., Samet, J. M., and Graves, L. M. (2003). Dependence of peroxisome proliferator-activated receptor ligand-induced mitogen-activated protein kinase signaling on epidermal growth factor receptor transactivation. J. Biol. Chem. 278, 46261–46269.
| Dependence of peroxisome proliferator-activated receptor ligand-induced mitogen-activated protein kinase signaling on epidermal growth factor receptor transactivation.Crossref | GoogleScholarGoogle Scholar | 12966092PubMed |
Hauser, S., Adelmant, G., Sarraf, P., Wright, H. M., Mueller, E., and Spiegelman, B. M. (2000). Degradation of the peroxisome proliferator-activated receptor γ is linked to ligand-dependent activation. J. Biol. Chem. 275, 18527–18533.
| Degradation of the peroxisome proliferator-activated receptor γ is linked to ligand-dependent activation.Crossref | GoogleScholarGoogle Scholar | 10748014PubMed |
Kim, K. H., Cho, Y. S., Park, J. M., Yoon, S. O., Kim, K. W., and Chung, A. S. (2007). Pro-MMP-2 activation by the PPARγ agonist, ciglitazone, induces cell invasion through the generation of ROS and the activation of ERK. FEBS Lett. 581, 3303–3310.
| Pro-MMP-2 activation by the PPARγ agonist, ciglitazone, induces cell invasion through the generation of ROS and the activation of ERK.Crossref | GoogleScholarGoogle Scholar | 17597617PubMed |
Kim, J., Sato, M., Li, Q., Lydon, J. P., Demayo, F. J., Bagchi, I. C., and Bagchi, M. K. (2008). Peroxisome proliferator-activated receptor gamma is a target of progesterone regulation in the preovulatory follicles and controls ovulation in mice. Mol. Cell. Biol. 28, 1770–1782.
| Peroxisome proliferator-activated receptor gamma is a target of progesterone regulation in the preovulatory follicles and controls ovulation in mice.Crossref | GoogleScholarGoogle Scholar | 18172011PubMed |
Komar, C. M. (2005). Peroxisome proliferator-activated receptors (PPARs) and ovarian function: implications for regulating steroidogenesis, differentiation, and tissue remodeling. Reprod. Biol. Endocrinol. 3, 41.
| Peroxisome proliferator-activated receptors (PPARs) and ovarian function: implications for regulating steroidogenesis, differentiation, and tissue remodeling.Crossref | GoogleScholarGoogle Scholar | 16131403PubMed |
Kowalewski, M. P., Dyson, M. T., Manna, P. R., and Stocco, D. M. (2009). Involvement of peroxisome proliferator-activated receptor gamma in gonadal steroidogenesis and steroidogenic acute regulatory protein expression. Reprod. Fertil. Dev. 21, 909–922.
| Involvement of peroxisome proliferator-activated receptor gamma in gonadal steroidogenesis and steroidogenic acute regulatory protein expression.Crossref | GoogleScholarGoogle Scholar | 19698295PubMed |
Kushwaha, R., Mishra, J., Gupta, A. P., Gupta, K., Vishwakarma, J., Chattopadhyay, N., Gayen, J. R., Kamthan, M., and Bandyopadhyay, S. (2018). Rosiglitazone up-regulates glial fibrillary acidic protein via HB-EGF secreted from astrocytes and neurons through PPARγ pathway and reduces apoptosis in high-fat diet-fed mice. J. Neurochem. 149, 679–698.
| Rosiglitazone up-regulates glial fibrillary acidic protein via HB-EGF secreted from astrocytes and neurons through PPARγ pathway and reduces apoptosis in high-fat diet-fed mice.Crossref | GoogleScholarGoogle Scholar | 30311190PubMed |
Kwintkiewicz, J., Nishi, Y., Yanase, T., and Giudice, L. C. (2010). Peroxisome proliferator-activated receptor-γ mediates bisphenol A inhibition of FSH-stimulated IGF-1, aromatase, and estradiol in human granulosa cells. Environ. Health Perspect. 118, 400–406.
| Peroxisome proliferator-activated receptor-γ mediates bisphenol A inhibition of FSH-stimulated IGF-1, aromatase, and estradiol in human granulosa cells.Crossref | GoogleScholarGoogle Scholar | 20064783PubMed |
Light, A., and Hammes, S. R. (2015). LH-induced steroidogenesis in the mouse ovary, but not testis, requires matrix metalloproteinase 2- and 9-mediated cleavage of upregulated EGF receptor ligands. Biol. Reprod. 93, 65.
| LH-induced steroidogenesis in the mouse ovary, but not testis, requires matrix metalloproteinase 2- and 9-mediated cleavage of upregulated EGF receptor ligands.Crossref | GoogleScholarGoogle Scholar | 26203177PubMed |
Livak, K. J., and Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25, 402–408.
| Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method.Crossref | GoogleScholarGoogle Scholar | 11846609PubMed |
Long, M. J., Sairam, M. R., and Komar, C. M. (2009). Initiation of the expression of peroxisome proliferator-activated receptor gamma (PPAR gamma) in the rat ovary and the role of FSH. Reprod. Biol. Endocrinol. 7, 145.
| Initiation of the expression of peroxisome proliferator-activated receptor gamma (PPAR gamma) in the rat ovary and the role of FSH.Crossref | GoogleScholarGoogle Scholar | 19968884PubMed |
Pogrmic-Majkic, K., Fa, S., Dakic, V., Kaisarevic, S., and Kovacevic, R. (2010). Upregulation of peripubertal rat Leydig cell steroidogenesis following 24 h in vitro and in vivo exposure to atrazine. Toxicol. Sci. 118, 52–60.
| Upregulation of peripubertal rat Leydig cell steroidogenesis following 24 h in vitro and in vivo exposure to atrazine.Crossref | GoogleScholarGoogle Scholar | 20667998PubMed |
Pogrmic-Majkic, K., Samardzija, D., Fa, S., Hrubik, J., Glisic, B., Kaisarevic, S., and Andric, N. (2014). Atrazine enhances progesterone production through activation of multiple signaling pathways in FSH-stimulated rat granulosa cells: evidence for premature luteinization. Biol. Reprod. 91, 124.
| Atrazine enhances progesterone production through activation of multiple signaling pathways in FSH-stimulated rat granulosa cells: evidence for premature luteinization.Crossref | GoogleScholarGoogle Scholar | 25253736PubMed |
Pogrmic-Majkic, K., Samardzija, D., Stojkov-Mimic, N., Vukosavljevic, J., Trninic-Pjevic, A., Kopitovic, V., and Andric, N. (2018). Atrazine suppresses FSH-induced steroidogenesis and LH-dependent expression of ovulatory genes through PDE-cAMP signaling pathway in human cumulus granulosa cells. Mol. Cell. Endocrinol. 461, 79–88.
| Atrazine suppresses FSH-induced steroidogenesis and LH-dependent expression of ovulatory genes through PDE-cAMP signaling pathway in human cumulus granulosa cells.Crossref | GoogleScholarGoogle Scholar | 28859905PubMed |
Richards, J. S., Russell, D. L., Ochsner, S., Hsieh, M., Doyle, K. H., Falender, A. E., Lo, Y. K., and Sharma, S. C. (2002). Novel signaling pathways that control ovarian follicular development, ovulation, and luteinization. Recent Prog. Horm. Res. 57, 195–220.
| Novel signaling pathways that control ovarian follicular development, ovulation, and luteinization.Crossref | GoogleScholarGoogle Scholar | 12017544PubMed |
Samardzija, D., Pogrmic-Majkic, K., Fa, S., Stanic, B., Jasnic, J., and Andric, N. (2018). Bisphenol A decreases progesterone synthesis by disrupting cholesterol homeostasis in rat granulosa cells. Mol. Cell. Endocrinol. 461, 55–63.
| Bisphenol A decreases progesterone synthesis by disrupting cholesterol homeostasis in rat granulosa cells.Crossref | GoogleScholarGoogle Scholar | 28859904PubMed |
Schneider, C. A., Rasband, W. S., and Eliceiri, K. W. (2012). NIH Image to ImageJ: 25 years of image analysis. Nat. Methods 9, 671–675.
| NIH Image to ImageJ: 25 years of image analysis.Crossref | GoogleScholarGoogle Scholar | 22930834PubMed |
Sepilian, V., and Nagamani, M. (2005). Effects of rosiglitazone in obese women with polycystic ovary syndrome and severe insulin resistance. J. Clin. Endocrinol. Metab. 90, 60–65.
| Effects of rosiglitazone in obese women with polycystic ovary syndrome and severe insulin resistance.Crossref | GoogleScholarGoogle Scholar | 15483106PubMed |
Seto-Young, D., Paliou, M., Schlosser, J., Avtanski, D., Park, A., Patel, P., Holcomb, K., Chang, P., and Poretsky, L. (2005). Direct thiazolidinedione action in the human ovary: insulin-independent and insulin-sensitizing effects on steroidogenesis and insulin-like growth factor binding protein-1 production. J. Clin. Endocrinol. Metab. 90, 6099–6105.
| Direct thiazolidinedione action in the human ovary: insulin-independent and insulin-sensitizing effects on steroidogenesis and insulin-like growth factor binding protein-1 production.Crossref | GoogleScholarGoogle Scholar | 16131582PubMed |
Seto-Young, D., Avtanski, D., Strizhevsky, M., Parikh, G., Patel, P., Kaplun, J., Holcomb, K., Rosenwaks, Z., and Poretsky, L. (2007). Interactions among peroxisome proliferator activated receptor-gamma, insulin signaling pathways, and steroidogenic acute regulatory protein in human ovarian cells. J. Clin. Endocrinol. Metab. 92, 2232–2239.
| Interactions among peroxisome proliferator activated receptor-gamma, insulin signaling pathways, and steroidogenic acute regulatory protein in human ovarian cells.Crossref | GoogleScholarGoogle Scholar | 17374711PubMed |
Seto-Young, D., Avtanski, D., Parikh, G., Suwandhi, P., Strizhevsky, M., Araki, T., Rosenwaks, Z., and Poretsky, L. (2011). Rosiglitazone and pioglitazone inhibit estrogen synthesis in human granulosa cells by interfering with androgen binding to aromatase. Horm. Metab. Res. 43, 250–256.
| Rosiglitazone and pioglitazone inhibit estrogen synthesis in human granulosa cells by interfering with androgen binding to aromatase.Crossref | GoogleScholarGoogle Scholar | 21321839PubMed |
Shimada, M., and Yamashita, Y. (2011). Cells during follicular development and ovulation process. J. Mamm. Ova Res. 28, 25–31.
| Cells during follicular development and ovulation process.Crossref | GoogleScholarGoogle Scholar |
Shkolnik, K., Tadmor, A., Ben-Dor, S., Nevo, N., Galiani, D., and Dekel, N. (2011). Reactive oxygen species are indispensable in ovulation. Proc. Natl Acad. Sci. U. S. A. 108, 1462–1467.
| Reactive oxygen species are indispensable in ovulation.Crossref | GoogleScholarGoogle Scholar | 21220312PubMed |
Tencer, L., Burgermeister, E., Ebert, M. P., and Liscovitch, M. (2008). Rosiglitazone induces caveolin-1 by PPARγ-dependent and PPRE-independent mechanisms: the role of EGF receptor signaling and its effect on cancer cell drug resistance. Anticancer Res. 28, 895–906.
| 18507034PubMed |
Tyagi, S., Sharma, S., Gupta, P., Saini, A., and Kaushal, C. (2011). The peroxisome proliferator-activated receptor: a family of nuclear receptors role in various diseases. J. Adv. Pharm. Technol. Res. 2, 236–240.
| The peroxisome proliferator-activated receptor: a family of nuclear receptors role in various diseases.Crossref | GoogleScholarGoogle Scholar | 22247890PubMed |
Vitti, M., Di Emidio, G., Di Carlo, M., Carta, G., Antonosante, A., Artini, P. G., Cimini, A., Tatone, C., and Benedetti, E. (2016). Peroxisome proliferator-activated receptors in female reproduction and fertility. PPAR Res. 2016, 4612306.
| Peroxisome proliferator-activated receptors in female reproduction and fertility.Crossref | GoogleScholarGoogle Scholar | 27559343PubMed |
Waite, K. J., Floyd, Z. E., Arbour-Reily, P., and Stephens, J. M. (2001). Interferon-γ-induced regulation of peroxisome proliferator-activated receptor γ and STATs in adipocytes. J. Biol. Chem. 276, 7062–7068.
| Interferon-γ-induced regulation of peroxisome proliferator-activated receptor γ and STATs in adipocytes.Crossref | GoogleScholarGoogle Scholar | 11106650PubMed |
Wayne, C. M., Fan, H.-Y., Cheng, X., and Richards, J. S. (2007). Follicle-stimulating hormone induces multiple signaling cascades: evidence that activation of Rous sarcoma oncogene, RAS, and the epidermal growth factor receptor are critical for granulosa cell differentiation. Mol. Endocrinol. 21, 1940–1957.
| Follicle-stimulating hormone induces multiple signaling cascades: evidence that activation of Rous sarcoma oncogene, RAS, and the epidermal growth factor receptor are critical for granulosa cell differentiation.Crossref | GoogleScholarGoogle Scholar | 17536007PubMed |
