Follicle-stimulating hormone regulation of microRNA expression on progesterone production in cultured rat granulosa cells

MicroRNAs (miRNAs) regulate gene expression post-transcriptionally by interacting with the 3′ untranslated regions of their target mRNAs. Previously, miRNAs have been shown to regulate genes involved in cell growth, apoptosis, and differentiation, but their role in ovarian granulosa cell follicle-stimulating hormone (FSH)-stimulated steroidogenesis is unclear. Here we show that expression of 31 miRNAs is altered during FSH-mediated progesterone secretion of cultured granulosa cells. Specifically, 12 h after FSH treatment, miRNAs mir-29a and mir-30d were significantly down-regulated. However, their expression increased after 48 h. Bioinformatic analysis used to predict potential targets of mir-29a and mir-30d revealed a wide array of potential mRNA target genes, including those encoding genes involved in multiple signaling pathways. Taken together, our results pointed to a novel mechanism for the pleiotropic effects of FSH.

[1]  Xiaoman Hong,et al.  Hormonal Regulation of MicroRNA Expression in Periovulatory Mouse Mural Granulosa Cells1 , 2008, Biology of reproduction.

[2]  A. Amsterdam,et al.  Control of differentiation, transformation, and apoptosis in granulosa cells by oncogenes, oncoviruses, and tumor suppressor genes. , 1997, Endocrine reviews.

[3]  Kathryn A. O’Donnell,et al.  c-Myc-regulated microRNAs modulate E2F1 expression , 2005, Nature.

[4]  Lew Steinberg,et al.  Feedback loop. , 2010, JEMS : a journal of emergency medical services.

[5]  N. Gilula,et al.  Cell-to-cell communication and ovulation. A study of the cumulus-oocyte complex , 1978, The Journal of cell biology.

[6]  Lynn Doucette-Stamm,et al.  A C . elegans genome-scale microRNA network contains composite feedback motifs with high flux capacity , 2008 .

[7]  Hugo Naya,et al.  Small RNAs analysis in CLL reveals a deregulation of miRNA expression and novel miRNA candidates of putative relevance in CLL pathogenesis , 2008, Leukemia.

[8]  E. Maizels,et al.  FSH signaling pathways in immature granulosa cells that regulate target gene expression: branching out from protein kinase A. , 2006, Cellular signalling.

[9]  A. Amsterdam,et al.  Novel genes modulated by FSH in normal and immortalized FSH‐responsive cells: new insights into the mechanism of FSH action , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[10]  C. Burge,et al.  Conserved Seed Pairing, Often Flanked by Adenosines, Indicates that Thousands of Human Genes are MicroRNA Targets , 2005, Cell.

[11]  Xiaoqing Tang,et al.  Identification of glucose-regulated miRNAs from pancreatic {beta} cells reveals a role for miR-30d in insulin transcription. , 2009, RNA.

[12]  B. O’Malley,et al.  Ovulation: a multi-gene, multi-step process , 2000, Steroids.

[13]  Shengshou Hu,et al.  MicroRNA: Novel Regulators Involved in the Remodeling and Reverse Remodeling of the Heart , 2008, Cardiology.

[14]  C. Villar,et al.  Programming of gene expression by Polycomb group proteins. , 2008, Trends in cell biology.

[15]  S. Grieshaber,et al.  Follicle-stimulating hormone-responsive cytoskeletal genes in rat granulosa cells: class I beta-tubulin, tropomyosin-4, and kinesin heavy chain. , 2003, Endocrinology.

[16]  Wei Yan,et al.  Cloning and expression profiling of small RNAs expressed in the mouse ovary. , 2007, RNA.

[17]  Aibin He,et al.  Overexpression of micro ribonucleic acid 29, highly up-regulated in diabetic rats, leads to insulin resistance in 3T3-L1 adipocytes. , 2007, Molecular endocrinology.

[18]  N. Ueno,et al.  A functional bone morphogenetic protein system in the ovary. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[19]  K. Zatloukal,et al.  miR‐29a suppresses tristetraprolin, which is a regulator of epithelial polarity and metastasis , 2009, EMBO reports.

[20]  J. Zeitlinger,et al.  Polycomb complexes repress developmental regulators in murine embryonic stem cells , 2006, Nature.

[21]  Xu Ma,et al.  A network of miRNAs expressed in the ovary are regulated by FSH. , 2009, Frontiers in bioscience.

[22]  Mark M Perry,et al.  Maternally imprinted microRNAs are differentially expressed during mouse and human lung development , 2007, Developmental dynamics : an official publication of the American Association of Anatomists.

[23]  M. Yamakuchi,et al.  MiR-34, SIRT1, and p53: The feedback loop , 2009, Cell cycle.

[24]  S. Sealfon,et al.  Microtranscriptome regulation by gonadotropin-releasing hormone , 2009, Molecular and Cellular Endocrinology.

[25]  Kiyoko F. Aoki-Kinoshita,et al.  From genomics to chemical genomics: new developments in KEGG , 2005, Nucleic Acids Res..

[26]  T. Tuschl,et al.  Identification of Novel Genes Coding for Small Expressed RNAs , 2001, Science.

[27]  Vincent De Guire,et al.  An E2F/miR-20a Autoregulatory Feedback Loop* , 2007, Journal of Biological Chemistry.

[28]  C. Sites,et al.  Adhesion Proteins Increase Cellular Attachment, Follicle-Stimulating Hormone Receptors, and Progesterone Production in Cultured Porcine Granulosa Cells , 1996, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[29]  Y. Yoshida,et al.  Crosstalk Among Multiple Signaling Pathways Controlling Ovarian Cell Death , 1999, Trends in Endocrinology & Metabolism.

[30]  R. Momota,et al.  The distribution of type IV collagen alpha chains in the mouse ovary and its correlation with follicular development. , 2007, Archives of histology and cytology.

[31]  M. Byrom,et al.  Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis , 2005, Nucleic acids research.

[32]  F. Slack,et al.  Small non-coding RNAs in animal development , 2008, Nature Reviews Molecular Cell Biology.

[33]  F. Slack,et al.  The time of appearance of the C. elegans let-7 microRNA is transcriptionally controlled utilizing a temporal regulatory element in its promoter. , 2003, Developmental biology.

[34]  M. Matzuk,et al.  Follicle stimulating hormone is required for ovarian follicle maturation but not male fertility , 1997, Nature Genetics.

[35]  P. Terranova,et al.  Relationship between the preovulatory luteinizing hormone (LH) surge and androstenedione synthesis of preantral follicles in the cyclic hamster: detection by in vitro responses to LH. , 1983, Biology of reproduction.

[36]  Harvey F Lodish,et al.  Myogenic factors that regulate expression of muscle-specific microRNAs. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[37]  Osamu Yoshino,et al.  Impaired microRNA processing causes corpus luteum insufficiency and infertility in mice. , 2008, The Journal of clinical investigation.

[38]  M. Ashburner,et al.  Gene Ontology: tool for the unification of biology , 2000, Nature Genetics.

[39]  J. Steitz,et al.  Switching from Repression to Activation: MicroRNAs Can Up-Regulate Translation , 2007, Science.

[40]  E. Adashi,et al.  The generation and characterization of an ovary-selective cDNA library , 2003, Molecular and Cellular Endocrinology.

[41]  M. Shmoish,et al.  Alterations in micro-ribonucleic acid expression profiles reveal a novel pathway for estrogen regulation. , 2008, Endocrinology.

[42]  A. Ben-Ze'ev,et al.  Coordinated regulation of morphological and biochemical differentiation in a steroidogenic cell: the granulosa cell model. , 1989, Trends in biochemical sciences.