Abstract
Purpose
To elucidate the promoter region of human decidual prolactin (dPRL) gene in the human endometrial stromal cells (ESC).
Methods
Various segments of the human dPRL promoter that direct the expression of the secreted alkaline phosphatase (SEAP) reporter gene were transfected into human ESC decidualized by estrogen (E) + progesterone (P) or cyclic AMP (cAMP) to identify E + P or cAMP responsive elements.
Results
The region between nucleotides −2038 and −1605 relative to the transcriptional initiation site includes two activator protein-1 (AP-1) sites, which both provided maximal response to E + P or cAMP in decidualized cells. When either AP-1 site was mutated, response in the promoter activity to both E + P or cAMP response showed a decrease compared with control. The region between −310 and −285 that contains consensus-binding sequences for transcription factors of CCAAT/Enhancer-binding proteins (C/EBP) contributed to E + P and cAMP response in decidualized cells. Also, the 5′-flanking region that extends 79 base pairs upstream, including an imperfect cAMP response element (CRE), contributed to E + P and cAMP response. In cells treated with E + P or cAMP for 10 days, mutant of C/EBP-binding site showed an increase in promoter activity comparing to dPRL-2038. In contrast, treatment with PKI showed a decrease in promoter activity in cells treated with E + P or cAMP alone.
Conclusions
These results suggest that cAMP-induced region of the human dPRL promoter resides between −1862 and −1856, −1703 and −1697, −310 and −285, and that the sequences between −1862 and −1856, −1703 and −1697 of the promoter display E + P-induced promoter activity. Furthermore, the current study indicates that E + P or cAMP cooperatively regulate the dPRL gene transcription through some transcriptional factors such as C/EBP, CREB, and other cofactor(s), and that some repressor(s) or corepressor(s) may be involved in the C/EBP-binding site of the human dPRL promoter.
Similar content being viewed by others
References
Tanaka K, Minoura H, Isobe T, Yonaha H, Kawato H, Wang DF, Yoshida T, Kojima M, Kangawa K, Toyoda N (2003) Ghrelin is involved in the decidualization of human endometrial stromal cells. J Clin Endocrinol Metab 88:2335–2340
Daly DC, Maslar IA, Riddick DH (1983) Prolactin production during in vitro decidualization of proliferative endometrium. Am J Obstet Gynecol 145:672–678
Brosens JJ, Takeda S, Acevedo CH, Lewis MP, Kirby PL, Symes EK, Krausz T, Purohit A, Gellersen B, White JO (1996) Human endometrial fibroblasts immortalized by simian virus 40 large T antigen differentiate in response to a decidualization stimulus. Endocrinology 137:2225–2231
Irwin JC, Kirk D, King RJ, Quigley MM, Gwatkin RB (1989) Hormonal regulation of human endometrial stromal cells in culture: an in vitro model for decidualization. Fertil Steril 52:761–768
Huang JR, Tseng L, Bischof P, Janne OA (1987) Regulation of prolactin production by progestin, estrogen, and relaxin in human endometrial stromal cells. Endocrinolgy 121:2011–2017
Tang B, Guller S, Gurpide E (1993) Cyclic adenosine 3′, 5′-monophosphate induces prolactin expression in stromal cells isolated from human proliferative endometrium. Endocrinology 133:2197–2203
Maslar IA, Kaplan BM, Luciano AA, Riddick DH (1980) Prolactin production by the endometrium of early human pregnancy. J Clin Endocrinol Metab 51:78–83
Maslar IA, Riddick DH (1979) Prolactin production by human endometrium during the normal menstrual cycle. Am J Obstet Gynecol 135:751–754
Daly DC, Maslar IA, Riddick DH (1983) Prolactin production during in vitro decidualization of proliferative endometrium. Am J Obstet Gynecol 145:672–678
Daly DC, Kuslis S, Riddick DH (1986) Evidence of short-loop inhibition of decidual prolactin synthesis by decidual proteins. Part I. Am J Obstet Gynecol 155:358–362
Truong AT, Duez C, Belayew A, Rennard A, Pictet R, Be GI, Martial JA (1984) Isolation and characterization of the human prolactin gene. EMBO J 3:429–437
Gellersen B, Dimattia GE, Friesen HG, Bohnet HG (1989) Porlactin (PRL) mRNA from human deciduas differs from pituitary PRL mRNA but resembles the IM-9-P3 lymphoblast PRL transcript. Mol Cell Endocrinol 64:127–130
Berwaer M, Martial JA, Davis JR (1994) Characterization of an up-stream promoter directing extrapituitary expression of the human prolactin gene. Mol Endocrinol 8:635–642
Gellersen B, Kempf R, Telgmann R, DiMattia GE (1994) Nonpituitary human prolactin gene transcription is independent of Pit-1 and differentially controlled in lymphocytes and in endometrial stroma. Mol Eedocrinol 8:356–373
Watanabe K, Kessler CA, Bachurski CJ, Kanda Y, Richardson BD, Stanek J, Handwerger S, Brar AK (2001) Identification of a decidua-specific enhancer on the human prolactin gene with two critical activator protein 1(AP-1) binding sites. Mol Endocrinol 15:638–653
Pohnke Y, Kempf R, Gellersen B (1999) CCAAT/enhancer-binding proteins are mediators in the protein kinase A-dependent activation of the decidual prolactin promoter. J Biol Chem 274:24808–24818
Tang B, Guller S, Gurpide E (1993) Mechanisms involved in the decidualization of human endometrial stromal cells. Acta Eur Fertil 24:221–223
Holinka CF (1988) Growth and hormonal responsiveness of human endometrial stromal cells in culture. Hum Cell 1:207–217
Feinman MA, Kliman HJ, Caltabiano S, Strauss JF (1986) 8-Bromo-3′,5′-adenosine monophosphate stimulates the endocrine activity of human cytotrophoblasts in culture. J Clin Endocrinol Metab 63:1211–1217
Pansini F, Bergamini CM, Bettocchi S Jr Malfaccini M, Santoiemma M, Scoppetta V, Bagni B, Mollica G (1984) Sex steroid hormones influence the cAMP content in human endometrium during the menstrual cycle. Gynecol Obstet Invest 18:174–177
Telgmann R, Maronde E, Tasken K, Gellersen B (1997) Activated protein kinase A is required for differentiation-dependent transcription of the decidual prolactin gene in human endometrial stromal cells. Endocrinology 138:929–937
Pfahl M (1993) Nuclear receptor/AP-1 interaction. Endocr Rev 14:651–658
Hyder SM, Nawaz Z, Chiappetta C, Yokoyama K, Stancel GM (1995) The protooncogene c-jun contains an unusual estrogen-inducible enhancer within the coding sequence. J Biol Chem 270:8506–8513
Webb P, Lopez GN, Uht RM, Kushner PJ (1995) Tamoxifen activation of the estrogen receptor/AP-1 pathway: potential origin for the cell-specific estrogen-like effects of antiestrogens. Mol Endocrinol 9:443–456
Bamberger AM, Bamberger CM, Gellersen B, Schulte HM (1996) Modulation of AP-1 activity by the human progesterone receptor in endometrial adenocarcinoma cells. Proc Natl Acad Sci U S A 93:6169–6174
Brar AK, Frank GR, Kessler CA, Cedars MI, Handwerger S (1997) Progesterone-dependent decidualization of the human endometrium is mediated by cAMP. Endocrine 6:301–307
Meyer TE, Habener JF (1993) Cyclic adenosine 3′,5′-onophosphate response element binding protein (CREB) and related transcription—activating deoxyribonucleic acid-binding proteins. Endocr Rev 14:269–290
Chrivia JC, Kwok RP, Lamb N, Hagiwara M, Montminy MR, Goodman RH (1993) Phosphorylated CREB binds specifically to the nuclear protein CBP. Nature 365:855–859
Niehof M, Manns MP, Trautwein C (1997) CREB controls LAP/C/EBP beta transcription. Mol Cell Biol 17:3600–3613
Arias J, Alberts AS, Brindle P, Claret FX, Smeal T, Karin M, Feramisco J, Montminy M (1994) Activation of cAMP and mitogen responsive genes relies on a common nuclear factor. Nature 370:226–229
Christian M, Zhang X, Schneider-Merck T, Unterman TG, Gellersen B, White JO, Brosens JJ (2002) Cyclic AMP-induced forkhead transcription factor, FKHR, cooperates with CCAAT/enhancer-binding protein beta in differentiating human endometrial stromal cells. J Biol Chem 277:20825–20832
Kasahara K, Takakura K, Takebayashi K, Kimura F, Nakanishi K, Noda Y (2001) The role of human chorionic gonadotropin on decidualization of endometrial stromal cells in vitro. J Clin Endocrinol Metab 86:1281–1286
Garzia E, Borgato S, Cozzi V, Doi P, Bulfamante G, Persani L, Cetin I (2004) Lack of expression of endometrial prolactin in early implantation failure: a pilot study. Hum Reprod 19:1911–1916
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Wang, D.F., Minoura, H., Sugiyama, T. et al. Analysis on the promoter region of human decidual prolactin gene in the progesterone-induced decidualization and cAMP-induced decidualization of human endometrial stromal cells. Mol Cell Biochem 300, 239–247 (2007). https://doi.org/10.1007/s11010-006-9388-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11010-006-9388-z