Skip to main content

Pit-1 Expression, Regulation, and Modulation of Multiple Pituitary Genes

  • Chapter
Gene Engineering in Endocrinology

Part of the book series: Contemporary Endocrinology ((COE,volume 22))

  • 97 Accesses

Abstract

Anterior pituitary development is a highly complex process whereby five distinct, mature cell types arise in a precise spatial and temporal pattern (1–3). Three of these cell types, somatotropes, lactotropes, and thyrotropes, are dependent on expression of the pituitary-specific transcription factor Pit-1/GHF-1 (4). In the mouse, the pituitary anlage is first detectable at d 12.5 postcoitum (12.5 p.c.) (5). Pit-1 transcripts are detectable throughout the anterior pituitary at d 13.5 p.c. Interestingly, Pit-1 protein is not detectable until d 15.5 p.c. This long lag time between Pit-1 RNA and protein expression indicates that the precise temporal control of Pit-1 expression is under translational as well as transcriptional control. Other homeobox proteins in other species appear to have similar dual control expression. Rapidly following expression of Pit-1 protein at d 15.5 p.c., transcripts for growth hormone (GH), prolactin (PRL), and the thyroid-stimulating hormone ß subunit (TSH0) are identified. The major expression of PRL, however, is not observed until after d 17.5 p.c. A second population of thyrotropes was identified in the rostral tip of the anterior pituitary by Lin and colleagues (6). These thyrotropes appear at embryonic d 12.5 (E12.5) long before any detectable expression of Pit-1 (E14.5). By postpartum d 0.5, these rostral thyrotropes are no longer detectable, and only the Pit-1-dependent caudomedial thyrotropes remain. The physiological significance of these early Pit-1-independent rostral tip thyrotropes is unknown.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Voss JW, Rosenfeld MG. Anterior pituitary development: short tales from dwarf mice. Cell 1992; 527530.

    Google Scholar 

  2. Andersen B, Rosenfeld MG. Pit-1 determines cell types during development of the anterior pituitary gland: a model for transcriptional regulation of cell phenotypes in mammalian organogenesis. J Biol Chem 1994; 269:29, 335–29, 338.

    Google Scholar 

  3. Borelli E. Pitfalls during development: controlling differentiation of the pituitary gland. Trends Genet 1989; 10: 222–224.

    Article  Google Scholar 

  4. Cohen LE, Wondisford FE, Radovick S. Role of Pit-1 in the gene expression of growth hormone, prolactin, and thyrotropin. Endocrin Metab Clin North Am 1996; 25: 523–540.

    Article  CAS  Google Scholar 

  5. Dolle P, Castrillo J, Theill LE, Deerinck T, Ellisman M, Karin M. Expression of GHF1 protein in Mouse pituitaries correlates both temporally and spatially with the onset of growth hormone gene activity. Cell 1990; 60: 809–820.

    Google Scholar 

  6. Lin S-C, Li S, Drolet DW, Rosenfeld MG. Pituitary ontogeny of the Snell dwarf mouse reveals Pit1-independent and Pit-l-dependent origins of the thyrotrope. Development 1994; 120: 515–522.

    PubMed  CAS  Google Scholar 

  7. Watanabe YG, Daikoku S. An immunohistochemical study of the cytogenesis of adenohypophysial cells in fetal rats. Dev Biol 1979; 68: 557–567.

    Article  PubMed  CAS  Google Scholar 

  8. Hoeffler JP, Boockfor FR, Frawley LS. Ontogeny of prolactin cells in neonatal rats: initial prolactin secretors also release growth hormone. Endocrinology 1985; 117: 187–195.

    Article  PubMed  CAS  Google Scholar 

  9. Gash D, Ahmad N, Schechter J. Comparison of gonadotroph, thyrotroph and mammotroph development in situ, in transplants and in organ culture. Neuroendocrinology 1982; 34: 222–228.

    Article  PubMed  CAS  Google Scholar 

  10. Simmons DM, Voss JW, Holloway JM, Broide RS, Rosenfeld MG, Swanson LW. Pituitary cell phenotypes involve cell-specific Pit-1 mRNA translation and synergistic interactions with other classes of transcription factors. Genes Dev 1990; 4: 695–711.

    Article  PubMed  CAS  Google Scholar 

  11. Puy LA, Asa SL. The ontogeny of Pit-1 expression in the human fetal pituitary gland. Neuroendocrinology 1996; 63: 349–355.

    Article  PubMed  CAS  Google Scholar 

  12. Ingraham H, Chen R, Mangalam HJ, Elsholtz HP, Flynn SE, Lin CR, Simmons DM, Swanson L, Rosenfeld MG. A tissue-specific transcription factor containing a homeodomain specifies a pituitary phenotype. Cell 1988; 55: 519–529.

    Article  PubMed  CAS  Google Scholar 

  13. Bodner M, Castrillo J, Theill LE, Deerinck T, Ellisman M, Karin M. The pituitary-specific transcription factor GHF-1 is a homeobox-containing protein. Cell 1988; 55: 505–518.

    Article  PubMed  CAS  Google Scholar 

  14. Lew AM, Elsholtz HP. Cloning of the human cDNA for transcription factor Pit-1. Nucleic Acids Res 1991; 19: 6329.

    Article  PubMed  CAS  Google Scholar 

  15. Tatsumi K, Notomi T, Amino N, Miyai K. Nucleotide sequence of the complementary DNA for human Pit-1/GHF1. Biochim Biophys Acta 1992; 1129: 231–234.

    Article  PubMed  CAS  Google Scholar 

  16. Wong EA, Silsby JL, El Halawani ME. Complementary DNA cloning and expression of Pit-1/GHF1 from the domestic turkey. DNA Cell Biol 1992; 11: 651–660.

    Article  PubMed  CAS  Google Scholar 

  17. Yamada S, Hata J, Yamashita S. Molecular cloning of fish Pit-1 cDNA and its functional binding to promoter of gene expressed in the pituitary. J Biol Chem 1993; 268:24, 361–24, 366.

    Google Scholar 

  18. Lorens JB, Aasland R, Brunstad H, Bergh H, Male R. Two variants of the pituitary specific transcription factor Pit-1 in Atlantic salmon. J Mol Endocrinol 1996; 17: 225–236.

    Article  PubMed  CAS  Google Scholar 

  19. Candiani S, Pestarino M. Expression of the tissue-specific transcription factor Pit-1 in the lancelet, Branchiostoma lanceolatum. J Comp Neurol 1998; 392: 343–351.

    Article  PubMed  CAS  Google Scholar 

  20. Malagon MM, Garrido JC, Dieulois C, Hera C, Castrillo JL, Dobado-Berrios PM, Gracia-Navarro F. Expression of the pituitary transcription factor GHF-1/Pit-1 in cell types of the adult porcine adenohypophysis. J Histochem Cytochem 1996; 44: 621–627.

    Article  PubMed  CAS  Google Scholar 

  21. Gordon DF, Haugen BR, Sarapura VDS, Nelson AR, Wood WM, Ridgway EC. Analysis of Pit-1 in regulating mouse TSHbeta promoter activity in thyrotropes. Mol Cell Endocrinol 1993; 96: 75–84.

    Article  PubMed  CAS  Google Scholar 

  22. Theill LE, Castrillo J, Wu D, Karin M. Dissection of functional domains of the pituitary specific transcription factor GHF1. Nature 1989; 342: 945–948.

    Article  PubMed  CAS  Google Scholar 

  23. Ingraham HA, Flynn SE, Voss JW, Albert VR, Kapiloff MS, Wilson L, Rosenfeld MG. The POU-specific domain of Pit-1 is essential for sequence-specific, high affinity DNA binding and DNA-dependent Pit-1-Pit-1 interactions. Cell 1990; 61: 1021–1033.

    Article  PubMed  CAS  Google Scholar 

  24. Sharp ZD. Rat Pit-1 stimulates transcription in vitro by influencing pre-initiation complex assembly. Biochem Biophys Res Commun 1995; 206: 40–45.

    Article  PubMed  CAS  Google Scholar 

  25. Liang J, Moye-Rowley S, Maurer R. In vivo mutational analysis of the DNA binding domain of the tissue-specific transcription factor, Pit-1. J Biol Chem 1995; 270:25,520–25,525.

    Google Scholar 

  26. Jacobson EM, Li P, Rosenfeld MG, Aggarwal AK. Crystallization and preliminary X-ray analysis of Pit-1 POU domain complexed to a 28 base pair DNA element. Proteins 1996; 24: 263–265.

    Article  PubMed  CAS  Google Scholar 

  27. Jacobson EM, Li P, Leon-del-Rio A, Rosenfeld MG, Aggarwal AK. Structure of Pit-1 POU domain bound to DNA as a dimer: unexpected arrangement and flexibility. Genes Dev 1997; 11: 198–212.

    Article  PubMed  CAS  Google Scholar 

  28. Klemm JD, Rould MA, Aurora R, Herr W, Pabo CO. Crystal structure of the Oct-1 POU domain bound to an octaamer site: DNA recognition with tethered DNA-binding modules. Cell 1994; 77: 21–32.

    Article  PubMed  CAS  Google Scholar 

  29. Camper SA, Saunders TL, Katz RW, Reeves RH. The Pit-1 transcription factor gene is a candidate for the murine snell dwarf mutation. Genomics 1990; 8: 586–590.

    Article  PubMed  CAS  Google Scholar 

  30. Li S, Crenshaw EB, Rawson EJ, Simmons DM, Swanson LW, Rosenfeld MG. Dwarf locus mutants lacking three pituitary cell types result from mutations in the POU-domain gene pit-l. Nature 1990; 347: 528–533.

    Article  PubMed  CAS  Google Scholar 

  31. Haugen BR, Ridgway EC. Transcription factor Pit-1 and its clinical implications: from bench to bedside. Endocrinologist 1995; 5: 132–139.

    Article  Google Scholar 

  32. Pellegrini-Bouiller I, Belicar P, Barlier A, Gunz G, Charvet J-P, Jaquet P, Brue T, Vialettes B, Enjalbert A. A new mutation of the gene encoding the transcription factor Pit-1 is responsible for combined pituitary hormone deficiency. J Clin Endocrinol Metab 1996; 81: 2790–2796.

    Article  PubMed  CAS  Google Scholar 

  33. Pernasetti F, Milner RDG, Al Ashwal AAZ, de Zegher F, Chavez VM, Muller M, Martial JA. Pro239Ser: a novel recessive mutation of the Pit-1 gene in seven middle eastern children with growth hormone, Prolactin and thyrotropin deficiency. J Clin Endocrinol Metab 1998; 83: 2079–2083.

    Google Scholar 

  34. Fofanova OV, Takamura N, Kinoshita E, Yoshimoto M, Tsuji Y, Peterkova VA, Evgrafov OV, Dedov II, Goncharov NP, Yamashita S. Rarity of Pit-1 involvement in children from Russia with combined pituitary hormone deficiency. Am J Med Genetics 1998; 77: 360–365.

    Article  CAS  Google Scholar 

  35. Buckwalter MS, Katz RW, Camper SA. Localization of the panhypopituitary dwarf mutation (df) on mouse chromosome 11 in an intersubspecific backcross. Genomics 1991; 10: 515–526.

    Article  PubMed  CAS  Google Scholar 

  36. Sornson MW, Wu W, Dasen JS, Flynn SE, Norman DJ, O’Connell SM, Gukovsky I, Corriere C, Ryan AK, Miller AP, Zuo L, Gleiberman AS, Andersen B, Beamer WG, Rosenfeld MG. Pituitary lineage determination by the Prophet of Pit-1 homeodomain factor defective in Ames dwarfism. Nature 1996; 384: 327–333.

    Article  PubMed  CAS  Google Scholar 

  37. Gage PJ, Brinkmeier ML, Scarlett LM, Knapp LT, Camper SA, Mahon KA. The Ames dwarf gene, df, is required early in pituitary ontogeny for the extinction of Rpx transcription and initiation of lineage-specific cell proliferation. Mol Endocrinol 1996; 10: 1570–1581.

    Article  PubMed  CAS  Google Scholar 

  38. Wu W, Cogan JD, Pfaffle RW, Dasen JS, Frisch H, O’Connell SM, Flynn SE, Brown MR, Mullis PE, Parks JS, Phillips JA III, Rosenfeld MG. Mutations in PROP1 cause familial combined pituitary hormone deficiency. Nat Genetics 1998; 18: 147–149.

    Article  CAS  Google Scholar 

  39. Fofanova 0, Takamura N, Kinoshita E, Parks JS, Brown MR, Peterkova VA, Evgrafov OV, Goncharov NP, Bulatov AA, Dedov II, Yamashita S. Compound heterozygous deletion of the PROP1 gene in children with combined pituitary hormone deficiency. J Clin Endocrinol Metab 1998; 83: 2601–2603.

    Google Scholar 

  40. Fofanova OV, Takamura N, Kinoshita E, Parks JS, Brown MR, Peterkova VA, Evgrafov OV, Goncharov NP, Bulatov AA, Dedov II, Yamashita S. A mutational hot spot in the PROP1 gene in Russian children with combined pituitary hormone deficiency. Pituitary 1998; 1: 45–49.

    Article  PubMed  CAS  Google Scholar 

  41. Morris AE, Kloss B, McChesney RE, Bancroft C, Chasin LA. An alternatively spliced Pit-1 isoform altered in its ability to trans-activate. Nucleic Acids Res 1992; 20: 1355–1361.

    Article  PubMed  CAS  Google Scholar 

  42. Konzak KE, Moore DD. Functional isoforms of Pit-1 generated by alternative mRNA splicing. Mol Endocrinol 1992; 6: 241–247.

    Article  PubMed  CAS  Google Scholar 

  43. Theill LE, Hattori K, Lazzaro D, Castrillo J-L, Karin M. Differential splicing of the GHF1 primary transcript gives rise to two functionally distinct homeodomain proteins. EMBO J 1992; 11: 2261–2269.

    PubMed  CAS  Google Scholar 

  44. Diamond SE, Gutierrez-Hartmann A. A 26-amino acid insertion domain defines a functional transcription switch motif in Pit-1 beta. J Biol Chem 1996; 271:28, 925–28, 932.

    Google Scholar 

  45. Haugen BR, Wood WM, Gordon DF, Ridgway EC. A thyrotrope-specific variant of Pit-1 transactivates the thyrotropin beta promoter. J Biol Chem 1993; 268:20, 818–20, 824.

    Google Scholar 

  46. Haugen BR, Gordon DF, Nelson AR, Wood WM, Ridgway EC. The combination of Pit-1 and Pit-1T have a synergistic stimulatory effect on the thyrotropin beta subunit promoter but not the growth hormone or prolactin promoters. Mol Endocrinol 1994; 8: 1574–1582.

    Article  PubMed  CAS  Google Scholar 

  47. Voss JW, Wilson L, Rhodes SJ, Rosenfeld MG. An alternative Pit-1 RNA splicing product reveals modular binding and non-modular transcriptional activities of the POU-specific domain. Mol Endocrinol 1993; 7: 1551–1560.

    Article  PubMed  CAS  Google Scholar 

  48. Day RN, Day KH. Specific repression of rat prolactin gene expression in transplanted tumor cells. Mol Endocrinol 1994; 8: 12–20.

    Article  PubMed  CAS  Google Scholar 

  49. Day RN, Day KH. An alternatively spliced form of Pit-1 represses prolactin gene expression. Mol Endocrinol 1994; 8: 374–381.

    Article  PubMed  CAS  Google Scholar 

  50. Schanke JT, Conwell CM, Durning M, Fisher JM, Golos TG. Pit-1/growth hormone factor 1 splice variant expression in the Rhesus monkey pituitary gland and the Rhesus and human placenta. J Clin Endocrinol Metab 1997; 82: 800–807.

    Article  PubMed  CAS  Google Scholar 

  51. Kurima K, Weatherly KL, Sharova L, Wong EA. Synthesis of turkey Pit-1 mRNA variants by alternative splicing and transcription initiation. DNA Cell Biol 1998; 17: 93–103.

    Article  PubMed  CAS  Google Scholar 

  52. Childs GV, Taub K, Jones KE, Chin WW. Triiodothyronine receptor beta-2 messenger ribonucleic acid expression by somatotropes and thyrotropes: effect of propylthiouracil-induced hypothyroidism in rats. Endocrinology 1991; 129: 2767–2773.

    Article  PubMed  CAS  Google Scholar 

  53. Chen R, Ingraham HA, Treacy MN, Albert VR, Wilson L, Rosenfeld MG. Autoregulation of pit-1 gene expression mediated by two cis-active promoter elements. Nature 1990; 346: 583–586.

    Article  PubMed  CAS  Google Scholar 

  54. McCormick A, Brady H, Theill LE, Karin M. Regulation of the pituitary-specific homeobox gene GHF1 by cell autonomous and environmental cues. Nature 1990; 345: 829–832.

    Article  PubMed  CAS  Google Scholar 

  55. Ohta K, Nobukuni Y, Mitsubuchi H, Ohta T, Tohma T, Jinno Y, Endo F, Matsuda I. Characterization of the gene encoding human pituitary-specific transcription factor, Pit-1. Gene 1992; 122: 387–388.

    Article  PubMed  CAS  Google Scholar 

  56. Gage PJ, Roller ML, Saunders TL, Scarlett LM, Camper SA. Anterior pituitary cells defective in the cell autonomous factor, df, undergo cell lineage specification but not expansion. Development 1996; 122: 151–160.

    PubMed  CAS  Google Scholar 

  57. DiMattia GE, Rhodes SJ, Krones A, Carriere C, O’Connell S, Kalla K, Arias C, Sawchenko P, Rosefeld MG. The Pit-1 gene is regulated by distinct early and late pituitary-specific enhancers. Dev Biol 1997; 182: 180–190.

    Article  PubMed  CAS  Google Scholar 

  58. Rhodes SJ, Chen R, DiMattia GE, Scully KM, Kalla KA, Lin SC, Yu VC, Rosenfeld MG. A tissue-specific enhancer confers Pit- 1-dependent morphogen inducibility and autoregulation on the Pit-1 gene. Genes Dev 1993; 7: 913–932.

    Article  PubMed  CAS  Google Scholar 

  59. Smith KP, Sharp ZD. A pit-1 binding site 3’ to the transcription start site inhibits transcription elongation in vitro. Biochem Biophys Res Commun 1991; 177: 790–796.

    Article  PubMed  CAS  Google Scholar 

  60. Sanchez-Pacheco A, Palomino T, Aranda A. Negative regulation of expression of the pituitary-specific transcription factor GHF-1/Pit-1 by thyroid hormones through interference with promoter enhancer elements. Mol Cell Biol 1995; 15: 6322–6330.

    PubMed  CAS  Google Scholar 

  61. Pfaffle RW, DiMattia GE, Parks JS, Brown MR, Wit JM, Jansen M, Van der Nat H, Van den Brande JL, Rosenfeld MG, Ingraham HA. Mutation of the POU-specific domain of Pit-1 and hypopituitarism without pituitary hypoplasia. Science 1992; 257: 1118–1121.

    Article  PubMed  CAS  Google Scholar 

  62. Rhodes SJ, Chen R, DiMattia GE, Scully KM, Kalla KA, Lin S-C, Yu VC, Rosenfeld MG. A tissue-specific enhancer confers Pit- 1-dependent morphogen inducibility and autoregulation on the pit-1 gene. Genes Dev 1993; 7: 913–932.

    Article  PubMed  CAS  Google Scholar 

  63. Rhodes SJ, Krones A, Nelson C, Rosenfeld MG. Function of the conserved Pit-1 gene distal enhancer in progenitor and differentiated pituitary cells. Mol Cell Endocrinol 1996; 124: 163–172.

    Article  PubMed  CAS  Google Scholar 

  64. Lefevre C, Imagawa M, Dana S, Grindlay J, Bodner M, Karin M. Tissue-specific expression of the growth hormone gene is conferred in part by binding of a specific trans-acting factor. EMBO J 1987; 6: 971–981.

    PubMed  CAS  Google Scholar 

  65. Lira SA, Kalla KA, Glass CK, Drolet DW, Rosenfeld MG. Synergistic interactions between Pit-1 and other elements are required for effective somatotroph rat growth hormone gene expression in transgenic mice. Mol Endocrinol 1993; 7: 694–701.

    Article  PubMed  CAS  Google Scholar 

  66. Lira SA, Crenshaw EB, Glass CK, Swanson LW, Rosenfeld MG. Identification of rat growth hormone sequences targeting pituitary expression in transgenic mice. Proc Natl Acad Sci USA 1988; 85: 4755–4759.

    Article  PubMed  CAS  Google Scholar 

  67. Schaufele F, West BL, Baxter JD. Synergistic activation of the rat growth hormone promoter by Pit-1 and the thyroid hormone receptor. Mol Endocrinol 1992; 6: 656–665.

    Article  PubMed  CAS  Google Scholar 

  68. Bodner M, Karin M. A pituitary-specific trans-acting factor can stimulate transcription from the growth hormone promoter in extracts of nonexpressing cells. Cell 1987; 50: 267–275.

    Article  PubMed  CAS  Google Scholar 

  69. Lipkin SM, Naar AM, Kalla KA, Sack RA, Rosenfeld MG. Identification of a novel zinc finger protein binding a conserved element critical for Pit-1 dependent growth hormone gene expression. Genes Dev 1993; 7: 1674–1687.

    Article  PubMed  CAS  Google Scholar 

  70. Mayo KE, Godfrey PA, Suhr ST, Kulik DJ, Rahal JO. Growth hormone releasing hormone: synthesis and signaling. Recent Prog Horm Res 1995; 50: 35–73.

    PubMed  CAS  Google Scholar 

  71. Force WR, Spindler SR. 3,5,3’-L-triiodothyronine (thyroid hormone)-induced protein-DNA interactions in the thyroid hormone response elements and cell type-specific elements of the rat growth hormone gene revealed by in vivo dimethyl sulfate footprinting. J Biol Chem 1994; 269: 9682–9686.

    PubMed  CAS  Google Scholar 

  72. Chang W, Zhou W, Theill LE, Baxter JD, Schaufele F. An activation function in Pit-1 required selectively for synergistic transcription. J Biol Chem 1996; 271:17, 733–17, 738.

    Google Scholar 

  73. Chuang FM, West BL, Baxter JD, Schaufele F. Activities in Pit-1 determine whether receptor interacting protein 140 activates or inhibits Pit-1/nuclear receptor transcriptional synergy. Mol Endocrinol 1997; 11: 1332–1341.

    Article  PubMed  CAS  Google Scholar 

  74. Schaufele F. CCAAT/Enhancer-binding protein alpha activation of the rat growth hormone promoter in pituitary progenitor GHFT1–5 cells. J Biol Chem 1996; 271:21, 484–21, 489.

    Google Scholar 

  75. Struthers RS, Gaddy-Kurten D, Vale WW. Activin inhibits binding of transcription factor Pit-1 to the growth hormone promoter. Proc Natl Acad Sci USA 1992; 89:11, 451–11, 455.

    Google Scholar 

  76. Tansey WP, Catanzaro DF. Spl and thyroid hormone receptor differentially activate expression of human growth hormone and chorionic somatomammotropin genes. J Biol Chem 1991; 266: 98059813.

    Google Scholar 

  77. Lemaigre FP, Lafontaine DA, Courtois SJ, Durviaux SM, Rousseau GG. Spl can displace GHF-1 from its distal binding site and stimulate transcription from the growth hormone promoter. Mol Cell Biol 1990; 10: 1811–1814.

    PubMed  CAS  Google Scholar 

  78. Nelson C, Albert V, Elsholtz 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: 1400–1405.

    Article  PubMed  CAS  Google Scholar 

  79. Iverson RA, Day KH, d’Emden M, Day RN, Maurer RA. Clustered point mutation analysis of the rat prolactin promoter. Mol Endocrinol 1990; 4: 1564–1571.

    Article  PubMed  CAS  Google Scholar 

  80. Crenshaw EB, Kalla K, Simmons DM, Swanson LW, Rosenfeld MG. Cell-specific expression of the prolactin gene in transgenic mice is controlled by synergistic interactions between promoter and enhancer elements. Genes Dev 1989; 3: 959–972.

    Article  PubMed  CAS  Google Scholar 

  81. Holloway JM, Szeto DP, Scully KM, Glass CK, Rosenfeld MG. Pit-1 binding to specific DNA sites as a monomer or dimer determines gene-specific use of a tyrosine-dependent synergy domain. Genes Dev 1995; 9: 1992–2006.

    Article  PubMed  CAS  Google Scholar 

  82. Nowakowski BE, Maurer RA. Multiple Pit-1 binding sites facilitate estrogen responsiveness of the prolactin gene. Mol Endocrinol 1994; 8: 1742–1749.

    Article  PubMed  CAS  Google Scholar 

  83. Bradford AP, Conrad KE, Wasylyk C, Wasylyk B, Gutierrez-Hartmann A. Functional interaction of c-ETS and GHF-1/Pit-1 mediates Ras activation of pituitary-specific gene expression: mapping of the essential c-ETS-1 domain. Mol Cell Biol 1995; 15: 2849–2857.

    PubMed  CAS  Google Scholar 

  84. Bradford AP, Conrad KE, Tran PH, Ostrowski MC, Gutierrez-Hartmann. GHF-1/Pit-1 functions as a cell-specific integrator of ras signaling by targeting the ras pathway to a composite Ets-1/GHF-1 response element. J Biol Chem 1996; 271:24, 639–24, 648.

    Google Scholar 

  85. Bradford AP, Wasylyk C, Wasylyk B, Gutierrez-Hartmann A. Interaction of Ets-1 and the POUhomeodomain protein GHF-1/Pit-1 reconstitutes pituitary-specific gene expression. Mol Cell Biol 1997; 17: 1065–1074.

    Google Scholar 

  86. Voss JW, Wilson L, Rosenfeld MG. POU-domain proteins Pit-1 and Oct-1 interact to form a heteromeric complex and can cooperate to induce expression of the prolactin promoter. Genes Dev 1991; 5: 1309–1320.

    Article  PubMed  CAS  Google Scholar 

  87. Bach I, Rhodes SJ, Pearse RV II, Heinzel T, Gloss B, Scully KM, Sawchenko PE, Rosenfeld MG. P-Lim, a LIM homeodomain factor, is expressed during pituitary organ and cell commitment and synergizes with Pit-1. Proc Natl Acad Sci USA 1995; 92: 2720–2724.

    Article  PubMed  CAS  Google Scholar 

  88. Yan G, Pan WT, Bancroft C. Thyrotropin-releasing hormone action on the prolactin promoter is mediated by the POU protein Pit-1. Mol Endocrinol 1991; 5: 535–541.

    Article  PubMed  CAS  Google Scholar 

  89. Day RN, Koioke S, Sakai M, Muramatsu M, Maurer RA. Both Pit-1 and the estrogen receptor are required for estrogen responsiveness of the rat prolactin gene. Mol Endocrinol 1990; 4: 1964–1971.

    Article  PubMed  CAS  Google Scholar 

  90. Day RN, Maurer RA. The distal enhancer of the rat prolactin gene contains elements conferring response to multiple hormones. Mol Endocrinol 1989; 3: 3–9.

    Article  PubMed  CAS  Google Scholar 

  91. Nalda AM, Martial JA, Muller M. The glucocorticoid receptor inhibits the human prolactin gene expression by interference with Pit-1 activity. Mol Cell Endocrinol 1997; 134: 129–137.

    Article  PubMed  CAS  Google Scholar 

  92. Drolet DW, Scully KM, Simmons DM, Wegner M, Chu K, Swanson LW, Rosenfeld MG. TEF, a transcription factor expressed specifically in the anterior pituitary during embryogenesis, defines a new class of leucine zipper proteins. Genes Dev 1991; 5: 1739–1753.

    Article  PubMed  CAS  Google Scholar 

  93. Bockman J, Bockers TM, Winter C, Wittkowski W, Winterhoff H, Deufel T, Kreutz MR. Thyrotropin expression in the hypophyseal pars tuberalis-specific cells is 3,5,3’-triiodothyronine, thyrotropinreleasing hormone and Pit-1 independent. Endocrinology 1997; 138: 1019–1028.

    Article  Google Scholar 

  94. Sakai T, Inoue K, Kurosumi K. Light and electron microscopic immunocytochemistry of TSH-like cells occurring in the pars tuberalis of the adult male rat. Arch Histol Cytol 1992; 55: 151–157.

    Article  PubMed  CAS  Google Scholar 

  95. Bergmann M, Wittkowski W, Hoffman K. Ultrastructural localization of thyrotropin (TSH)-like immunoreactivity in specific secretory cells of the hypophyseal pars tuberalis in the Djungarian hamster, Phodopus sungorus. Cell Tissue Res 1989; 256: 649–652.

    PubMed  CAS  Google Scholar 

  96. Voss JW, Yao T, Rosenfeld MG. Alternative translation initiation site usage results in two structurally distinct forms of Pit-1. J Biol Chem 1991; 266:12, 832–12, 835.

    Google Scholar 

  97. Wood WM, Kao MY, Gordon DF, Ridgway EC. Thyroid hormone regulates the mouse thyrotropin beta subunit gene promoter in transfected primary thyrotropes. J Biol Chem 1989; 264:14, 840–14, 847.

    Google Scholar 

  98. Wood WM, Ocran KW, Kao MY, Gordon DF, Alexander LM, Gutierrez-Hartmann A, Ridgway EC. Protein factors in thyrotropic tumor nuclear extracts bind to a region of the mouse thyrotropin beta-subunit promoter essential for expression in thyrotropes. Mol Endocrinol 1990; 4: 1897–1904.

    Article  PubMed  CAS  Google Scholar 

  99. Haugen BR, McDermott MT, Gordon DF, Rupp CL, Wood WM, Ridgway EC. Determinants of thyrotrope-specific TSH-beta promoter activation: cooperation of Pit-1 with another factor. J Biol Chem 1996; 271: 385–389.

    Article  PubMed  CAS  Google Scholar 

  100. Steinfelder HJ, Radovick S, Mroczynski MA, Hauser P, McClaskey JH, Weintraub BD, Wondisford FE. Role of a pituitary-specific transcription factor (Pit-1/GHF1) or a closely related protein in cAMP regulation of human thyrotropin-beta subunit gene expression. J Clin Invest 1992; 89: 409–419.

    Article  PubMed  CAS  Google Scholar 

  101. Mason ME, Friend KE, Copper J, Shupnik MA. Pit-1/GHF-1 binds to TRH-sensitive regions of the rat thyrotropin beta gene. Biochemistry 1993; 32: 8932–8938.

    Article  PubMed  CAS  Google Scholar 

  102. Haugen BR, Gordon DF, Wood WM, Sarapura VD, Ridgway EC. Pit-1T and/or Pit-1 are necessary for basal Tshbeta promoter activity in thyrotropes. 76`“ Annual meeting of the Endocrine Society, Anaheim, CA, abstract #788, 1994.

    Google Scholar 

  103. Tremblay JJ, Lanctot C, Drouin J. The pan-pituitary activator of transcription, Ptxl (pituitary homeobox 1), acts in synergy with SF-1 and Pit-1 and is an upstream regulator of the Lim-homeodomain gene Lim3/Lhx3. Mol Endocrinol 1998; 12: 428–441.

    Article  PubMed  CAS  Google Scholar 

  104. Steinfelder HJ, Radovick S, Wondisford FE. Hormonal regulation of the thyrotropin beta-subunit gene by phosphorylation of the pituitary-specific transcription factor Pit-1. Proc Natl Acad Sci USA 1992; 89: 5942–5945.

    Article  PubMed  CAS  Google Scholar 

  105. Gordon DF, Lewis SR, Haugen BR, James A, McDermott MT, Wood WM, Ridgway EC. Pit-1 and GATA-2 interact and functionally cooperate to activate the thyrotropin beta subunit promoter. J Biol Chem 1997; 272:24, 339–24, 347.

    Google Scholar 

  106. Lai J-S, Herr W. Ethidium bromide provides a simple tool for identifying genuine DNA-independent protein associations. Proc Natl Acad Sci USA 1992; 89: 6958–6962.

    Article  PubMed  CAS  Google Scholar 

  107. Shupnik MA, Rosenzweig BA, Showers MO. Interactions of thyrotropin-releasing hormone, phorbol ester, and forskolin-sensitive regions of the rat thyrotropin-beta gene. Mol Endocrinol 1990; 4: 829836.

    Google Scholar 

  108. Shupnik MA, Rosenzweig BA, Friend KE, Mason ME. Thyrotropin (TSH)-releasing hormone-responsive elements in the rat Tshbeta gene have distinct biological and nuclear protein-binding properties. Mol Endocrinol 1992; 6: 43–52.

    Article  PubMed  CAS  Google Scholar 

  109. Steinfelder HJ, Hauser P, Nakayama Y, Radovick S, McClaskey JH, Taylor T, Weintraub BD, Wondisford FE. Thyrotropin-releasing hormone regulation of human Tshbeta expression: role of a pituitary-specific transcription factor (Pit-1/GHF-1) and potential interaction with a thyroid hormone-inhibitory element. Proc Natl Acad Sci USA 1991; 88: 3130–3134.

    Article  PubMed  CAS  Google Scholar 

  110. Kim MK, McClaskey JH, Bodenner DL, Weintraub BD. An AP-1-like factor and the pituitary-specific factor Pit-1 are both necessary to mediate hormonal induction of human thyrotropin beta gene expression. J Biol Chem 1993; 268:23, 366–23, 375.

    Google Scholar 

  111. Hodin RA, Lazar MA, Wintman BI, Darling DS, Koenig RJ, Moore DD, Chin WW. Identification of a thyroid hormone receptor that is pituitary-specific. Science 1989; 244: 76–79.

    Article  PubMed  CAS  Google Scholar 

  112. Wood WM, Ocran KO, Gordon DF, Ridgway EC. Isolation and characterization of mouse complementary DNAs encoding alpha and beta thyroid hormone receptors from thyrotrope cells: the mouse pituitary specific beta-2 isoform differs at the amino terminus from the corresponding species from rat pituitary tumor cells. Mol Endocrinol 1991; 5: 1049–1061.

    Article  PubMed  CAS  Google Scholar 

  113. Schwartz HL, Lazar MA, Oppenheimer JH. Widespread distribution of immunoreactive thyroid hormone beta-2 receptor in the nuclei of extrapituitary rat tissues. J Biol Chem 1994; 269:24, 77724, 782.

    Google Scholar 

  114. Wood WM, Dowding JM, Haugen BR, Bright TM, Gordon DF, Ridgway EC. Structural and functional characterization of the genomic locus encoding the murine beta2 thyroid hormone receptor. Mol Endocrinol 1994; 8: 1605–1617.

    Article  PubMed  CAS  Google Scholar 

  115. Wood WM, Dowding JM, Bright TM, McDermott MT, Haugen BR, Gordon DF, Ridgway EC. Thyroid hormone receptor beta2 promoter activity in pituitary cells is regulated by Pit-1. J Biol Chem 1996; 271:24, 213–24, 220.

    Google Scholar 

  116. Petersenn S, Rasch AC, Heyens M, Schulte HM. Structure and regulation of the human growth hormone-releasing hormone receptor gene. Mol Endocrinol 1998; 12: 233–247.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2000 Springer Science+Business Media New York

About this chapter

Cite this chapter

Haugen, B.R., Gordon, D.F., Wood, W.M. (2000). Pit-1 Expression, Regulation, and Modulation of Multiple Pituitary Genes. In: Shupnik, M.A. (eds) Gene Engineering in Endocrinology. Contemporary Endocrinology, vol 22. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-221-0_4

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-221-0_4

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-147-9

  • Online ISBN: 978-1-59259-221-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics