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Gene Review

Pou1f1  -  POU class 1 homeobox 1

Rattus norvegicus

Synonyms: GHF-1, GHF1, GHF1A, Ghf-1, Growth hormone factor 1, ...
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Disease relevance of Pou1f1

  • In this study, adenovirus was used to deliver rat Pit-1 to mouse liver [1].
  • Pit-1a mRNA was detected in GH3 rat pituitary tumor cells at levels about 1/7 that of Pit-1 mRNA [2].
  • It seems possible that over-expression of the pituitary cell-specific transcription factor Pit-1/GHF-1 (Pit-1) gene in response to active alpha(S) subunits contributes to the formation of these adenomas [3].
  • Moreover, the multistep correlation analysis revealed that the expression of nuclear Pit-1 was the strongest predictor of prolactinoma development [4].
  • Pituitary-specific transcription factor Pit-1 in the rdw rat with growth hormone- and prolactin-deficient dwarfism [5].

High impact information on Pou1f1

  • Pit-1 expression in heterologous cells (HeLa) selectively activates prolactin and growth hormone fusion gene expression, suggesting that Pit-1 is sufficient to confer a characteristic pituitary phenotype [6].
  • Pit-1 mRNA is expressed exclusively in the anterior pituitary gland in both somatotroph and lactotroph cell types, which produce growth hormone and prolactin, respectively [6].
  • The predicted GHF-1 sequence contains a region, near its C-terminus, that exhibits considerable similarity to a homeobox consensus sequence [7].
  • DNA complementary to Pit-1 mRNA, cloned on the basis of specific binding to AT-rich cell-specific elements in the rat prolactin and growth hormone genes, encodes a 33 kd protein with significant similarity at its carboxyl terminus to the homeodomains encoded by Drosophila developmental genes [6].
  • Transcription and transfection analyses in vitro using wild-type and mutated promoters indicate that Pit-1 can positively autoregulate the expression of the pit-1 promoter as a consequence of binding to two Pit-1-binding elements [8].

Chemical compound and disease context of Pou1f1

  • Immunolocalization of Pit-1 in gonadotroph nuclei is indicative of the transdifferentiation of gonadotroph to lactotroph cells in prolactinomas induced by estrogen [4].

Biological context of Pou1f1

  • We describe a naturally occurring isoform of GHF-1, GHF-2, in which an additional 26 amino acids are inserted into the activation domain of the protein as a result of alternative splicing [9].
  • The POU domain protein GHF-1 has a critical role in generation, proliferation and phenotypic expression of three pituitary cell types [9].
  • Analysis of the genomic GHF1 gene shows that most of the distinct functional domains of GHF-1 (and GHF-2) are encoded by separate exons [9].
  • Three of these regions (positions -41 to -58, -113 to -124, and -149 to -156) correspond to previously identified binding sites for the pituitary-specific, homeobox protein, Pit-1/GHF-1 [10].
  • PRL gene expression is dependent on the presence of the pituitary-specific transcription factor GHF-1/Pit-1, which is transcribed in a highly restricted manner in cells of the anterior pituitary [11].

Anatomical context of Pou1f1

  • For this purpose we have used nonpituitary HeLa cells, which do not express GHF-1 [11].
  • Pit-1 expression was detected in the majority (50-80%) of hepatocyte nuclei after tail vein injection (2 x 10(9) plaque forming units) [1].
  • Transcripts for Pit-1 (GHF-1), a transcription factor important in regulation of pituitary PRL, were not detected in hypothalamus or any of the extrahypothalamic brain parts [12].
  • To directly examine potential interactions, cotransfection studies using PRL distal enhancer reporter gene constructs and expression vectors for Pit-1 and rat estrogen receptor were performed in two heterologous cell lines [13].
  • In stably transfected CHO cells which accumulated approximately equal levels of either of the two proteins, Pit-1 trans-activated a prolactin promoter-driven CAT construct, while Pit-1a yielded no detectable transactivation, implying a trans-activation ratio for Pit-1a/Pit-1 of less than 0.05 [2].

Associations of Pou1f1 with chemical compounds


Physical interactions of Pou1f1


Regulatory relationships of Pou1f1


Other interactions of Pou1f1


Analytical, diagnostic and therapeutic context of Pou1f1


  1. Pituitary transcription factor-1 induces transient differentiation of adult hepatic stem cells into prolactin-producing cells in vivo. Lee, E.J., Russell, T., Hurley, L., Jameson, J.L. Mol. Endocrinol. (2005) [Pubmed]
  2. An alternatively spliced Pit-1 isoform altered in its ability to trans-activate. Morris, A.E., Kloss, B., McChesney, R.E., Bancroft, C., Chasin, L.A. Nucleic Acids Res. (1992) [Pubmed]
  3. Constitutively active G(S) alpha-subunits stimulate Pit-1 promoter activity via a protein kinase A-mediated pathway acting through deoxyribonucleic acid binding sites both for Pit-1 and for adenosine 3',5'-monophosphate response element-binding protein. Gaiddon, C., Tian, J., Loeffler, J.P., Bancroft, C. Endocrinology (1996) [Pubmed]
  4. Immunolocalization of Pit-1 in gonadotroph nuclei is indicative of the transdifferentiation of gonadotroph to lactotroph cells in prolactinomas induced by estrogen. Mukdsi, J.H., De Paul, A.L., Muñoz, S., Aoki, A., Torres, A.I. Histochem. Cell Biol. (2004) [Pubmed]
  5. Pituitary-specific transcription factor Pit-1 in the rdw rat with growth hormone- and prolactin-deficient dwarfism. Ono, M., Harigai, T., Furudate, S. J. Endocrinol. (1994) [Pubmed]
  6. A tissue-specific transcription factor containing a homeodomain specifies a pituitary phenotype. Ingraham, H.A., Chen, R.P., Mangalam, H.J., Elsholtz, H.P., Flynn, S.E., Lin, C.R., Simmons, D.M., Swanson, L., Rosenfeld, M.G. Cell (1988) [Pubmed]
  7. The pituitary-specific transcription factor GHF-1 is a homeobox-containing protein. Bodner, M., Castrillo, J.L., Theill, L.E., Deerinck, T., Ellisman, M., Karin, M. Cell (1988) [Pubmed]
  8. Autoregulation of pit-1 gene expression mediated by two cis-active promoter elements. Chen, R.P., Ingraham, H.A., Treacy, M.N., Albert, V.R., Wilson, L., Rosenfeld, M.G. Nature (1990) [Pubmed]
  9. Differential splicing of the GHF1 primary transcript gives rise to two functionally distinct homeodomain proteins. Theill, L.E., Hattori, K., Lazzaro, D., Castrillo, J.L., Karin, M. EMBO J. (1992) [Pubmed]
  10. Clustered point mutation analysis of the rat prolactin promoter. Iverson, R.A., Day, K.H., d'Emden, M., Day, R.N., Maurer, R.A. Mol. Endocrinol. (1990) [Pubmed]
  11. Synergistic activation of the prolactin promoter by vitamin D receptor and GHF-1: role of the coactivators, CREB-binding protein and steroid hormone receptor coactivator-1 (SRC-1). Castillo, A.I., Jimenez-Lara, A.M., Tolon, R.M., Aranda, A. Mol. Endocrinol. (1999) [Pubmed]
  12. The rat prolactin gene is expressed in brain tissue: detection of normal and alternatively spliced prolactin messenger RNA. Emanuele, N.V., Jurgens, J.K., Halloran, M.M., Tentler, J.J., Lawrence, A.M., Kelley, M.R. Mol. Endocrinol. (1992) [Pubmed]
  13. Both Pit-1 and the estrogen receptor are required for estrogen responsiveness of the rat prolactin gene. Day, R.N., Koike, S., Sakai, M., Muramatsu, M., Maurer, R.A. Mol. Endocrinol. (1990) [Pubmed]
  14. Effects of estrogen and epidermal growth factor on prolactin and Pit-1 mRNA in GH3 cells. Zhang, K., Kulig, E., Jin, L., Lloyd, R.V. Proc. Soc. Exp. Biol. Med. (1993) [Pubmed]
  15. In vivo and in vitro regulation of pituitary transcription factor-1 (Pit-1) by changes in the hormone environment. González-Parra, S., Chowen, J.A., García-Segura, L.M., Argente, J. Neuroendocrinology (1996) [Pubmed]
  16. Multiple Pit-1-binding sites facilitate estrogen responsiveness of the prolactin gene. Nowakowski, B.E., Maurer, R.A. Mol. Endocrinol. (1994) [Pubmed]
  17. Sperm 1: a POU-domain gene transiently expressed immediately before meiosis I in the male germ cell. Andersen, B., Pearse, R.V., Schlegel, P.N., Cichon, Z., Schonemann, M.D., Bardin, C.W., Rosenfeld, M.G. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  18. Involvement of a Pit-1 binding site in the regulation of the rat somatostatin receptor 1 gene expression. Baumeister, H., Meyerhof, W. Ann. N. Y. Acad. Sci. (1998) [Pubmed]
  19. Regulation of the pituitary-specific transcription factor GHF-1/Pit-1 messenger ribonucleic acid levels by growth hormone-secretagogues in rat anterior pituitary cells in monolayer culture. Soto, J.L., Castrillo, J.L., Dominguez, F., Dieguez, C. Endocrinology (1995) [Pubmed]
  20. The transcriptional regulation of the growth hormone gene is conserved in vertebrate evolution. Argenton, F., Vianello, S., Bernardini, S., Jacquemin, P., Martial, J., Belayew, A., Colombo, L., Bortolussi, M. Biochem. Biophys. Res. Commun. (1993) [Pubmed]
  21. Estrogen-modulated estrogen receptor x Pit-1 protein complex formation and prolactin gene activation require novel protein synthesis. Ying, C., Lin, D.H. J. Biol. Chem. (2000) [Pubmed]
  22. Inhibition of prolactin gene transcription by transforming growth factor-beta in GH3 cells. Delidow, B.C., Billis, W.M., Agarwal, P., White, B.A. Mol. Endocrinol. (1991) [Pubmed]
  23. Selective constraints on the activation domain of transcription factor Pit-1. Majumdar, S., Irwin, D.M., Elsholtz, H.P. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
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