PMID- 21212137 OWN - NLM STAT- MEDLINE DCOM- 20110601 LR - 20211020 IS - 1944-9917 (Electronic) IS - 0888-8809 (Print) IS - 0888-8809 (Linking) VI - 25 IP - 3 DP - 2011 Mar TI - A role for nuclear factor interleukin-3 (NFIL3), a critical transcriptional repressor, in down-regulation of periovulatory gene expression. PG - 445-59 LID - 10.1210/me.2010-0250 [doi] AB - The LH surge triggers dramatic transcriptional changes in genes associated with ovulation and luteinization. The present study investigated the spatiotemporal expression of nuclear factor IL-3 (NFIL3), a transcriptional regulator of the basic leucine zipper transcription factor superfamily, and its potential role in the ovary during the periovulatory period. Immature female rats were injected with pregnant mare's serum gonadotropin, treated with human chorionic gonadotropin (hCG), and ovaries or granulosa cells were collected at various times after hCG. Nfil3 mRNA was highly induced both in intact ovaries and granulosa cells after hCG treatment. In situ hybridization demonstrated that Nfil3 mRNA was highly induced in theca-interstitial cells at 4-8 h after hCG, localized to granulosa cells at 12 h, and decreased at 24 h. Overexpression of NFIL3 in granulosa cells inhibited the induction of prostaglandin-endoperoxide synthase 2 (Ptgs2), progesterone receptor (Pgr), epiregulin (Ereg), and amphiregulin (Areg) and down-regulated levels of prostaglandin E2. The inhibitory effect on Ptgs2 induction was reversed by NFIL3 small interfering RNA treatment. In theca-interstitial cells the expression of hydroxyprostaglandin dehydrogenase 15-(nicotinamide adenine dinucleotide) (Hpgd) was also inhibited by NFIL3 overexpression. Data from luciferase assays demonstrated that NFIL3 overexpression decreased the induction of the Ptgs2 and Areg promoter activity. EMSA and chromatin immunoprecipitation analyses indicated that NFIL3 binds to the promoter region containing the DNA-binding sites of cAMP response element binding protein and CCAAT enhancer binding protein-beta. In summary, hCG induction of NFIL3 expression may modulate the process of ovulation and theca-interstitial and granulosa cell differentiation by regulating expression of PTGS2, PGR, AREG, EREG, and HPGD, potentially through interactions with cAMP response element binding protein and CCAAT enhancer binding protein-beta on their target gene promoters. FAU - Li, Feixue AU - Li F AD - College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 310036, People's Republic of China. FAU - Liu, Jing AU - Liu J FAU - Jo, Misung AU - Jo M FAU - Curry, Thomas E Jr AU - Curry TE Jr LA - eng GR - R01 HD057446/HD/NICHD NIH HHS/United States GR - P20 RR015592/RR/NCRR NIH HHS/United States GR - P20 RR 15592/RR/NCRR NIH HHS/United States GR - HD051727/HD/NICHD NIH HHS/United States GR - HD057446/HD/NICHD NIH HHS/United States GR - R03 HD051727/HD/NICHD NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20110106 PL - United States TA - Mol Endocrinol JT - Molecular endocrinology (Baltimore, Md.) JID - 8801431 RN - 0 (AREG protein, human) RN - 0 (Amphiregulin) RN - 0 (Areg protein, rat) RN - 0 (Chorionic Gonadotropin) RN - 0 (EGF Family of Proteins) RN - 0 (EREG protein, human) RN - 0 (Epiregulin) RN - 0 (Ereg protein, rat) RN - 0 (Glycoproteins) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (NFIL3 protein, rat) RN - 0 (Receptors, Progesterone) RN - 0 (Repressor Proteins) RN - 62229-50-9 (Epidermal Growth Factor) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - EC 1.14.99.1 (PTGS2 protein, human) SB - IM MH - Amphiregulin MH - Animals MH - Blotting, Western MH - Cells, Cultured MH - Chorionic Gonadotropin/pharmacology MH - Chromatin Immunoprecipitation MH - Cyclooxygenase 2/genetics/metabolism MH - Down-Regulation/drug effects MH - EGF Family of Proteins MH - Electrophoretic Mobility Shift Assay MH - Epidermal Growth Factor/genetics/metabolism MH - Epiregulin MH - Female MH - Gene Expression Regulation/drug effects MH - Glycoproteins/genetics/metabolism MH - Granulosa Cells MH - Humans MH - In Situ Hybridization MH - Intercellular Signaling Peptides and Proteins/genetics/metabolism MH - Mutagenesis, Site-Directed MH - Oligonucleotide Array Sequence Analysis MH - Ovary/drug effects/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, Progesterone/genetics/metabolism MH - Repressor Proteins/genetics/*metabolism MH - Reverse Transcriptase Polymerase Chain Reaction PMC - PMC3045738 EDAT- 2011/01/08 06:00 MHDA- 2011/06/02 06:00 PMCR- 2012/03/01 CRDT- 2011/01/08 06:00 PHST- 2011/01/08 06:00 [entrez] PHST- 2011/01/08 06:00 [pubmed] PHST- 2011/06/02 06:00 [medline] PHST- 2012/03/01 00:00 [pmc-release] AID - me.2010-0250 [pii] AID - ME-10-0250 [pii] AID - 10.1210/me.2010-0250 [doi] PST - ppublish SO - Mol Endocrinol. 2011 Mar;25(3):445-59. doi: 10.1210/me.2010-0250. Epub 2011 Jan 6.