Genetic Elements Regulating Human Placental Lactogen Expression

  • Susan L. Fitzpatrick
  • William H. Walker
  • Grady F. Saunders
Conference paper
Part of the Serono Symposia, USA Norwell, Massachusetts book series (SERONOSYMP)


Human placental lactogen (hPL), also known aschorionic somatomammotropin (hCS), is specifically expressed in placental syncytiotrophoblast cells (1, 2). The levels of hPL increase during pregnancy such that by the third trimester this hormone accounts for 10% of the placental protein and greater than 5% of the mRNA (3, 4) and is the most abundant peptide hormone produced in primates (5). However, the biological role of hPL is still not clearly understood. It is believed to play a role in regulating maternal metabolism (reviewed in 6); however, the lack of biological defects in pregnancies lacking hPL (reviewed in 7) suggests that its function may be redundant or only required in particular circumstances; for example, maternal nutritional states. Nevertheless, the high amount of hPL mRNA during pregnancy and its tissue-specific expression suggest that it is a highly regulated system of gene expression.


Enhancer Activity Growth Hormone Gene Human Placental Lactogen Placental Protein SV40 Enhancer 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Sciarra JJ, Kaplan SL, Gumbach MM. Localization of anti-human growth hormone serum within the human placenta: evidence for a human chorionic growth hormone-prolactin. Nature 1963;199:1005–6.PubMedCrossRefGoogle Scholar
  2. 2.
    McWilliams D, Boime I. Cytological localization of placental lactogen messenger ribonucleic acid in syncytiotrophoblast layers of human placenta. Endocrinology 1980;107:761–5.PubMedCrossRefGoogle Scholar
  3. 3.
    Seeburg PH, Shine J, Martial JA, Ullrich A, Baxter JD, Goodman HM. Nucleotide sequence of part of the gene for human chorionic somatomam–motropin: purification of DNA complementary to predominant mRNA species. Cell 1977;12:157–65.PubMedCrossRefGoogle Scholar
  4. 4.
    Barrera-Saldana HA, Robberson DL, Saunders GF. Transcriptional products of the human placental lactogen gene. J Biol Chem 1982;257:12399–404.PubMedGoogle Scholar
  5. 5.
    Kaplan SL, Gurpide E, Sciarra JJ, Guumbach MM. Metabolic clearance rate and production rate of chorionic growth hormone–prolactin in late pregnancy. J Clin Endocrinol Metab 1968;28:1450–60.PubMedCrossRefGoogle Scholar
  6. 6.
    Talamantes R, Ogren L. The placenta as an endocrine organ: polypeptides. In: Knobil E, Neill J, eds. The physiology of reproduction. New York: Raven Press, 1988:2093–144.Google Scholar
  7. 7.
    Walker WH, Fitzpatrick SL, Barrera-Saldana HA, Resendez-Perez D, Saunders GF. The human placental lactogen genes: structure, function, evolution and transcriptional regulation. Endocr Rev 1991; 12: 316–28.PubMedCrossRefGoogle Scholar
  8. 8.
    Kidd VJ, Saunders GF. Linkage arrangement of human placental lactogen and growth hormone genes. J Biol Chem 1982;257:10673–80.PubMedGoogle Scholar
  9. 9.
    Barsh GS, Seeburg PH, Gelinas RE. The human growth hormone gene family: structure and evolution of the chromosomal locus. Nucleic Acids Res 1983;11:3939–58.PubMedCrossRefGoogle Scholar
  10. 10.
    Chen EY, Liao Y-C, Smith DH, Barrera-Saldana HA, Gelinas RE, Seeburg PH. The human growth hormone locus nucleotide sequence biology, and evolution. Genomics 1989; 4: 479–97.PubMedCrossRefGoogle Scholar
  11. 11.
    Nelson C, Crenshaw EB III, Franco R, et al. Discretecis-active genomic sequence dictate the pituitary cell type-specific expression of rat prolactin and growth hormone genes. Nature 1986;322:557–62.PubMedCrossRefGoogle Scholar
  12. 12.
    Bodner M, Castrillo J-L, Theill LE, Deerinck T, Ellisman M, Karin M. The pituitary-specific transcription factor GHF-1 is a homeobox-containing protein. Cell 1988;55:505–18.PubMedCrossRefGoogle Scholar
  13. 13.
    Nelson C, Albert VR, Elshotz HP, Lu LIW, Rosenfeld MG. Activation of cell-specific expression of rat growth hormone and prolactin genes by a common transcription factor. Science 1988;239:1400–5.PubMedCrossRefGoogle Scholar
  14. 14.
    Castrillo J-L, Bodner M, Karin M. Purification of growth hormone-specific transcription factor GHF-1 containing homeobox. Science 1989;243:814–7.PubMedCrossRefGoogle Scholar
  15. 15.
    Mangalam JH, Albert VR, Ingraham HA, et al. A pituitary POU domain protein, Pit-1, activates both growth hormone and prolactin promoters transcriptionally. Genes Dev 1989;3:946–58.PubMedCrossRefGoogle Scholar
  16. 16.
    Lemaigre FP, Peers BD, Lafontaine DA, et al. Pituitary–specific factor binding to the human prolactin growth hormone, and placental lactogen genes. DNA 1989;8:149–59.PubMedCrossRefGoogle Scholar
  17. 17.
    Cattini PA, Eberhardt NL. Regulated expression of chimaeric genes containing the 5’-flanking regions of human growth hormone-related genes in transiently transfected rat anterior pituitary tumor cells. Nucleic Acids Res 1987;15:1297–309.PubMedCrossRefGoogle Scholar
  18. 18.
    Rogers BL, Sobnosky MG, Saunders GF. Transcriptional enhancer within the human placental lactogen and growth hormone multigene cluster. Nucleic Acids Res 1986;14:7647–59.PubMedCrossRefGoogle Scholar
  19. 19.
    Walker WH, Fitzpatrick SL, Saunders GF. Sequences responsible for human placental lactogen enhancer activity and binding of placental specific nuclear proteins. J Biol Chem 1990;265;12940–8.PubMedGoogle Scholar
  20. 20.
    Gorman CM, Moffat LF, Howard BH. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol 1982;2:1044–51.PubMedGoogle Scholar
  21. 21.
    Gorman CM, Laimons L, Merlino GT, Gruss P, Khoury G, Howard BH. A novel system using the expression of chloramphenicol acetyltransferase in eukaryotic cells allows the quantitative study of promoter elements. In: Kumar A, ed. Eukaryotic gene expression. New York: Plenum Press, 1984:129–39.Google Scholar
  22. 22.
    Graham R, van der Eb A. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology 1973;52:456–7.PubMedCrossRefGoogle Scholar
  23. 23.
    Hall CV, Jacob PE, Ringold GM, Lee L. Expression and regulation ofEscherichia coli lac Z gene fusions in mammalian cells. J Mol Appl Genet 1983;2:101–9.PubMedGoogle Scholar
  24. 24.
    Dynan WS, Tjian R. The promoter-specific transcription factor Spl binds to upstream sequences in the SV40 early promoter. Cell 1983;35:79–87.PubMedCrossRefGoogle Scholar
  25. 25.
    Kadonaga JT, Jones KA, Tjian R. Promoter-specific activation of RNA polymerase II transcription by Spl. Trends Biochem 1986;11:20–3.CrossRefGoogle Scholar
  26. 26.
    Dignam JD, Lebovitz RM, Roeder RG. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res 1983;11:1475–89.PubMedCrossRefGoogle Scholar
  27. 27.
    Fitzpatrick SL, Walker WH, Saunders GF. DNA sequences involved in the transcriptional activation of a human placental lactogen gene. Mol Endocrinol 1990;4:1815–26.PubMedCrossRefGoogle Scholar
  28. 28.
    Fried M, Crothers DM. Equilibrium and kinetics of the lac repressor-operator interactions by polyacrylamide gel electrophoresis. Nucleic Acids Res 1981;9:6505–25.PubMedCrossRefGoogle Scholar
  29. 29.
    Garner MM, Revzin A. A gel electrophoresis method for quantifying binding of proteins to specific DNA regions: application to components of theEscherichia coli lactose operon regulatory system. Nucleic Acids Res 1981;9:3047–60.PubMedCrossRefGoogle Scholar
  30. 30.
    Letovsky J, Dynan WS. Measurement of the binding of transcription factor Spl to a single GC box recognition sequence. Nucleic Acids Res 1989;17:2639–53.PubMedCrossRefGoogle Scholar
  31. 31.
    Jones KA, Kadonaga JT, Luciw PA, Tjian R. Activation of the AIDs retrovirus promoter by the cellular transcription factor Spl. Science 1986;232:755–9.PubMedCrossRefGoogle Scholar
  32. 32.
    Evans T, Dechiara T, Efstratiadis A. A promoter of the rat insulin-like growth factor II gene consists of minimal control elements. J Mol Biol 1988;199:61–81.PubMedCrossRefGoogle Scholar
  33. 33.
    Pugh BR, Tjian R. Mechanism of transcriptional activation by Spl: evidence for coactivators. Cell 1990;61:1187–97.PubMedCrossRefGoogle Scholar
  34. 34.
    Garcia A, Wu FK, Mitsuyasu R, Gaynor RB. Interactions of cellular proteins involved in the transcriptional regulation of the human immunodeficiency virus. EMBO J 1987;6:3761–70.PubMedGoogle Scholar
  35. 35.
    Harrich D, Garcia J, Wu F, Mitsuyasu R, Gonzalez J, Gaynor R. Role of Sp1-binding domains in in vivo transcriptional regulation of the human immunodificiency virus type 1 long terminal repeat. J Virol 1989;63:2585–91.PubMedGoogle Scholar
  36. 36.
    Davidson I, Xiao JH, Rosales R, Staub A, Chambon P. The HeLa cell protein TEF-1 binds specifically, cooperatively to two SV40 enhancer motifs of unrelated sequence. Cell 1988;54:931–9.PubMedCrossRefGoogle Scholar
  37. 37.
    Xiao JH, Davidson I, Matthes H, Garnier J-M, Chambon P. Cloning, expression, and transcriptional properties of the human enhancer factor TEF-1. Cell 1991;65:551–68.PubMedCrossRefGoogle Scholar
  38. 38.
    Ishiji T, Lace MJ, Parkkinen S, et al. Transcriptional enhancer factor (TEF)-1 and its cell-specific co-activator activate human papillomavirus-16E6 andE7 oncogene transcription in keratinocytes and cervical carcinoma cells. EMBO J 1992;11:2271–81.PubMedGoogle Scholar
  39. 39.
    Tansey WP, Catanzaro DF. Spl and thyroid hormone receptor differentially activate expression of human growth hormone and chorionic somatomam-motropin genes. J Biol Chem 1991;266:9805–13.PubMedGoogle Scholar
  40. 40.
    Vox ML, Peers B, Belayew A, Martial JA. Characterization of an unusual thyroid response unit in the promoter of the human placental lactogen gene. J Biol Chem 1991;266:13397–408.Google Scholar
  41. 41.
    Nickel BE, Cattini PA. Tissue-specific expression and thyroid hormone regulation of the endogenous placental growth hormone variant and chorionic somatomammotropin genes in a human choriocarcinoma cell line. Endocrinology 1991;128:2353–9.PubMedCrossRefGoogle Scholar
  42. 42.
    Leidig F, Shepard AR, Zhang W, et al. Thyroid hormone responsiveness in human growth hormone-related genes: possible correlation with receptor-induced DNA conformational changes. J Biol Chem 1992;267:913–21.PubMedGoogle Scholar

Copyright information

© Springer-Verlag New York, Inc. 1993

Authors and Affiliations

  • Susan L. Fitzpatrick
  • William H. Walker
  • Grady F. Saunders

There are no affiliations available

Personalised recommendations