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Gene Review

POU1F1  -  POU class 1 homeobox 1

Homo sapiens

Synonyms: CPHD1, GHF-1, GHF1, Growth hormone factor 1, PIT-1, ...
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Disease relevance of POU1F1


Psychiatry related information on POU1F1


High impact information on POU1F1

  • In contrast to individuals with POU1F1 mutations, those with PROP1 mutations cannot produce LH and FSH at a sufficient level and do not enter puberty spontaneously [7].
  • Cretinism with combined hormone deficiency caused by a mutation in the PIT1 gene [8].
  • Pit-1 is monomeric in solution but associates as a dimer on its DNA response element, exhibiting DNA-dependent protein-protein interactions requiring the POUS domain [9].
  • Transcriptional activity of Pit-1 on enhancer elements is conferred primarily by a Ser- and Thr-rich N-terminal region unrelated to other known transcription-activating motifs [9].
  • Addition of GHF-1-containing fractions to HeLa extracts stimulates hGH promoter activity [10].

Chemical compound and disease context of POU1F1


Biological context of POU1F1

  • CONCLUSIONS: Our data suggest that the phenotype associated with POU1F1 mutations may be more variable, with the occasional preservation of TSH secretion [13].
  • Functional studies have revealed that POU1F1 (E230K) is associated with a reduction in transactivation, although DNA-binding affinity is similar to the wild-type protein [13].
  • Methods: Consequences of this mutation on transcriptional activities by transfection studies in alphaT3 cells, DNA binding ability by EMSA, structural properties, and nuclear accumulation of POU1F1 were investigated [14].
  • Most of the patients with this phenotype have either a dominant negative mutation in codon 271 (R271W) or are homozygous for a recessive mutation in the POU1F1 gene; to date only one case has been reported with compound heterozygosity for two point mutations [15].
  • Additionally, we describe two novel mutations within POU1F1, an insertion of a single base pair (ins778A) and a missense mutation (R172Q) [13].

Anatomical context of POU1F1

  • The POU1F1 gene encodes a transcription factor that is important for the development and differentiation of the cells producing GH, prolactin, and TSH in the anterior pituitary gland [16].
  • Its activity in COS-7 cells is enhanced by cotransfection of the pituitary-specific transcription factor Pit-1 [17].
  • We investigated the functional properties of Pitx2 missense mutants previously reported in Axenfeld-Rieger syndrome, using reporter genes under the control of pituitary target gene [human (h)PRL, hGH, hPit-1] promoters transfected in nonpituitary and pituitary cell lines [18].
  • The sequence of fragments amplified from rat spleen and from human bone marrow completely matched published sequences of rat and human pituitary Pit-1, respectively [19].
  • The GHF1 gene is expressed exclusively in cells of the somatotrophic lineage, and its transcription is extinguished in somatic cell hybrids [20].

Associations of POU1F1 with chemical compounds

  • Additionally, our data revealed POU1F1 mutations in three patients who were diagnosed as having ACTH deficiency but who, on further evaluation, were found to have normal cortisol secretion [13].
  • Several cases of mutations in the Pit-1 gene have been reported; the most common one is a sporadic mutation altering an arginine (R) to a tryptophan (W) in codon 271, in one allele of the Pit-1 gene [3].
  • Molecular analysis of genomic DNA for Pit-1 revealed the presence of compound heterozygous recessive mutations: a nonsense mutation in codon 172 and a novel missense mutation substituting glycine for glutamate at codon 174 [21].
  • Defective retinoic acid regulation of the Pit-1 gene enhancer: a novel mechanism of combined pituitary hormone deficiency [22].
  • A substitution of T go G induced a change from a Phe to a Cys residue at position 135 within the hydrophobic core of the POU-specific DNA-binding domain of the Pit-1 protein [23].

Physical interactions of POU1F1

  • Experiments with hGH deletion constructs reveal that binding sites for transcription factor AP-2 and the pituitary-specific factor GHF-1 are not required for forskolin stimulation, but that GHF-1 may potentiate the effect [24].
  • Conclusions: Together with previous data, our study indicates that both DNA binding and interaction with cofactors like cAMP response element-binding protein-binding protein are critical for POU1F1 function and that functional and structural properties of abnormal POU1F1 proteins are variously influenced by the type of mutations [14].
  • The presence of Pit-1-binding sites in the CS-A and GH-V promoter regions predicts that Pit-1 may be expressed in the placenta [25].
  • Three regions within the 5'-flanking region of the TSH beta gene have A-T-rich sequences which have sequence similarity to binding sites for the pituitary-specific POU domain transcription factor Pit-1/GHF-1 [26].
  • Pit-1/GHF-1 binds to TRH-sensitive regions of the rat thyrotropin beta gene [26].

Regulatory relationships of POU1F1

  • AP-1 and Oct-1 transcription factors down-regulate the expression of the human PIT1/GHF1 gene [27].
  • As shown in this cell system, the mutant LHX4 proteins predicted by the defect identified in patients fail to bind to and subsequently activate the POU1F1 regulatory sequence, but do not impair the ability of normal LHX4 to activate this target [28].
  • Based upon the results of this study, we propose a model in which the TGGGTCA-specific AP-1-like factor functionally cooperates with the tissue-specific factor Pit-1 to activate the hTSH beta gene [29].
  • CONCLUSIONS: Pit-1 mRNA transcripts are expressed mainly in prolactin and GH pituitary adenomas, but are also found in other adenomas and in the nontumorous adult human pituitary [30].
  • The PBMC of a PIT-1-negative woman expressed only the hGH-V transcript, but not the hGH-N one as expected [31].

Other interactions of POU1F1

  • However, induction by T3 was independent of either Sp1 or GH-1/Pit-1 binding in the site II region [32].
  • Among patients with combined pituitary hormone deficiency, hormonal deficiencies were of pituitary origin in all with PROP-1 and PIT-1 mutations and suggestive of hypothalamic origin in 81% without mutations [33].
  • Expression of the HESX1 gene precedes expression of PROP1 and PIT1, and it is much more widespread [34].
  • CONCLUSIONS: Such findings are consistent with the existence, in humans, of an LHX4-driven pathway leading to the expression of GH through transcriptional activation of POU1F1 [28].
  • We studied the PIT1 gene in a patient with combined deficiency of TSH, GH and PRL [35].

Analytical, diagnostic and therapeutic context of POU1F1


  1. Prop-1 gene expression in human pituitary tumors. Nakamura, S., Ohtsuru, A., Takamura, N., Kitange, G., Tokunaga, Y., Yasunaga, A., Shibata, S., Yamashita, S. J. Clin. Endocrinol. Metab. (1999) [Pubmed]
  2. Transcription factors regulating pituitary development. Parks, J.S., Brown, M.R. Growth Horm. IGF Res. (1999) [Pubmed]
  3. Description of a Brazilian patient bearing the R271W Pit-1 gene mutation. Rodrigues Martineli, A.M., Braga, M., De Lacerda, L., Raskin, S., Graf, H. Thyroid (1998) [Pubmed]
  4. Induction of GH, PRL, and TSH beta mRNA by transfection of Pit-1 in a human pituitary adenoma-derived cell line. Miyai, S., Yoshimura, S., Iwasaki, Y., Takekoshi, S., Lloyd, R.V., Osamura, R.Y. Cell Tissue Res. (2005) [Pubmed]
  5. Genetic basis of congenital hypothyroidism: abnormalities in the TSHbeta gene, the PIT1 gene, and the NIS gene. Tatsumi, K., Miyai, K., Amino, N. Clin. Chem. Lab. Med. (1998) [Pubmed]
  6. Positive association between POU1F1 and mental retardation in young females in the Chinese Han population. Sun, Y., Zhang, F., Gao, J., Gao, X., Guo, T., Zhang, K., Shi, Y., Zheng, Z., Tang, W., Zheng, Y., Li, S., Li, X., Feng, G., Shen, X., He, L. Hum. Mol. Genet. (2006) [Pubmed]
  7. Mutations in PROP1 cause familial combined pituitary hormone deficiency. Wu, W., Cogan, J.D., Pfäffle, R.W., Dasen, J.S., Frisch, H., O'Connell, S.M., Flynn, S.E., Brown, M.R., Mullis, P.E., Parks, J.S., Phillips, J.A., Rosenfeld, M.G. Nat. Genet. (1998) [Pubmed]
  8. Cretinism with combined hormone deficiency caused by a mutation in the PIT1 gene. Tatsumi, K., Miyai, K., Notomi, T., Kaibe, K., Amino, N., Mizuno, Y., Kohno, H. Nat. Genet. (1992) [Pubmed]
  9. The POU-specific domain of Pit-1 is essential for sequence-specific, high affinity DNA binding and DNA-dependent Pit-1-Pit-1 interactions. Ingraham, H.A., Flynn, S.E., Voss, J.W., Albert, V.R., Kapiloff, M.S., Wilson, L., Rosenfeld, M.G. Cell (1990) [Pubmed]
  10. A pituitary-specific trans-acting factor can stimulate transcription from the growth hormone promoter in extracts of nonexpressing cells. Bodner, M., Karin, M. Cell (1987) [Pubmed]
  11. Impact of gsp oncogene on the expression of genes coding for Gsalpha, Pit-1, Gi2alpha, and somatostatin receptor 2 in human somatotroph adenomas: involvement in octreotide sensitivity. Barlier, A., Pellegrini-Bouiller, I., Gunz, G., Zamora, A.J., Jaquet, P., Enjalbert, A. J. Clin. Endocrinol. Metab. (1999) [Pubmed]
  12. Expression of Pit-1 mRNA and activin/inhibin subunits in clinically nonfunctioning pituitary adenomas. In situ hybridization and immunohistochemical analysis. Sanno, N., Teramoto, A., Sugiyama, M., Matsuno, A., Takumi, I., Tahara, S., Osamura, R.Y. Horm. Res. (1998) [Pubmed]
  13. Novel mutations within the POU1F1 gene associated with variable combined pituitary hormone deficiency. Turton, J.P., Reynaud, R., Mehta, A., Torpiano, J., Saveanu, A., Woods, K.S., Tiulpakov, A., Zdravkovic, V., Hamilton, J., Attard-Montalto, S., Parascandalo, R., Vella, C., Clayton, P.E., Shalet, S., Barton, J., Brue, T., Dattani, M.T. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
  14. Identification and Functional Analysis of the Novel S179R POU1F1 Mutation Associated with Combined Pituitary Hormone Deficiency. Miyata, I., Vallette-Kasic, S., Saveanu, A., Takeuchi, M., Yoshikawa, H., Tajima, A., Tojo, K., Reynaud, R., Gueydan, M., Enjalbert, A., Tajima, N., Eto, Y., Brue, T. J. Clin. Endocrinol. Metab. (2006) [Pubmed]
  15. Combined pituitary hormone deficiency caused by compound heterozygosity for two novel mutations in the POU domain of the Pit1/POU1F1 gene. Hendriks-Stegeman, B.I., Augustijn, K.D., Bakker, B., Holthuizen, P., van der Vliet, P.C., Jansen, M. J. Clin. Endocrinol. Metab. (2001) [Pubmed]
  16. The de novo Q167K mutation in the POU1F1 gene leads to combined pituitary hormone deficiency in an Italian patient. Malvagia, S., Poggi, G.M., Pasquini, E., Donati, M.A., Pela, I., Morrone, A., Zammarchi, E. Pediatr. Res. (2003) [Pubmed]
  17. Structure and regulation of the human growth hormone-releasing hormone receptor gene. Petersenn, S., Rasch, A.C., Heyens, M., Schulte, H.M. Mol. Endocrinol. (1998) [Pubmed]
  18. Regulation of prolactin, GH, and Pit-1 gene expression in anterior pituitary by Pitx2: An approach using Pitx2 mutants. Quentien, M.H., Pitoia, F., Gunz, G., Guillet, M.P., Enjalbert, A., Pellegrini, I. Endocrinology (2002) [Pubmed]
  19. The transcription factor Pit-1/GHF-1 is expressed in hemopoietic and lymphoid tissues. Delhase, M., Vergani, P., Malur, A., Hooghe-Peters, E.L., Hooghe, R.J. Eur. J. Immunol. (1993) [Pubmed]
  20. The pituitary-specific regulatory gene GHF1 contains a minimal cell type-specific promoter centered around its TATA box. McCormick, A., Brady, H., Fukushima, J., Karin, M. Genes Dev. (1991) [Pubmed]
  21. Central hypothyroidism reveals compound heterozygous mutations in the Pit-1 gene. Brown, M.R., Parks, J.S., Adess, M.E., Rich, B.H., Rosenthal, I.M., Voss, T.C., VanderHeyden, T.C., Hurley, D.L. Horm. Res. (1998) [Pubmed]
  22. Defective retinoic acid regulation of the Pit-1 gene enhancer: a novel mechanism of combined pituitary hormone deficiency. Cohen, L.E., Zanger, K., Brue, T., Wondisford, F.E., Radovick, S. Mol. Endocrinol. (1999) [Pubmed]
  23. A new mutation of the gene encoding the transcription factor Pit-1 is responsible for combined pituitary hormone deficiency. Pellegrini-Bouiller, I., Bélicar, P., Barlier, A., Gunz, G., Charvet, J.P., Jaquet, P., Brue, T., Vialettes, B., Enjalbert, A. J. Clin. Endocrinol. Metab. (1996) [Pubmed]
  24. Induction of human growth hormone promoter activity by the adenosine 3',5'-monophosphate pathway involves a novel responsive element. Dana, S., Karin, M. Mol. Endocrinol. (1989) [Pubmed]
  25. Expression of pit-1 messenger ribonucleic acid and protein in the human placenta. Bamberger, A.M., Bamberger, C.M., Pu, L.P., Puy, L.A., Loh, Y.P., Asa, S.L. J. Clin. Endocrinol. Metab. (1995) [Pubmed]
  26. Pit-1/GHF-1 binds to TRH-sensitive regions of the rat thyrotropin beta gene. Mason, M.E., Friend, K.E., Copper, J., Shupnik, M.A. Biochemistry (1993) [Pubmed]
  27. AP-1 and Oct-1 transcription factors down-regulate the expression of the human PIT1/GHF1 gene. Delhase, M., Castrillo, J.L., de la Hoya, M., Rajas, F., Hooghe-Peters, E.L. J. Biol. Chem. (1996) [Pubmed]
  28. Functional relationship between LHX4 and POU1F1 in light of the LHX4 mutation identified in patients with pituitary defects. Machinis, K., Amselem, S. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
  29. 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. Kim, M.K., McClaskey, J.H., Bodenner, D.L., Weintraub, B.D. J. Biol. Chem. (1993) [Pubmed]
  30. Pituitary specific transcription factor messenger ribonucleic expression in adenomatous and nontumorous human pituitary tissues. Lloyd, R.V., Jin, L., Chandler, W.F., Horvath, E., Stefaneanu, L., Kovacs, K. Lab. Invest. (1993) [Pubmed]
  31. Both pituitary and placental growth hormone transcripts are expressed in human peripheral blood mononuclear cells (PBMC). Melen, L., Hennen, G., Dullaart, R.P., Heinen, E., Igout, A. Clin. Exp. Immunol. (1997) [Pubmed]
  32. Sp1 and thyroid hormone receptor differentially activate expression of human growth hormone and chorionic somatomammotropin genes. Tansey, W.P., Catanzaro, D.F. J. Biol. Chem. (1991) [Pubmed]
  33. Pituitary magnetic resonance imaging and function in patients with growth hormone deficiency with and without mutations in GHRH-R, GH-1, or PROP-1 genes. Osorio, M.G., Marui, S., Jorge, A.A., Latronico, A.C., Lo, L.S., Leite, C.C., Estefan, V., Mendonca, B.B., Arnhold, I.J. J. Clin. Endocrinol. Metab. (2002) [Pubmed]
  34. Heritable disorders of pituitary development. Parks, J.S., Brown, M.R., Hurley, D.L., Phelps, C.J., Wajnrajch, M.P. J. Clin. Endocrinol. Metab. (1999) [Pubmed]
  35. A novel E250X mutation of the PIT1 gene in a patient with combined pituitary hormone deficiency. Irie, Y., Tatsumi, K., Ogawa, M., Kamijo, T., Preeyasombat, C., Suprasongsin, C., Amino, N. Endocr. J. (1995) [Pubmed]
  36. Screening for PIT1 abnormality by PCR direct sequencing method. Irie, Y., Tatsumi, K., Kusuda, S., Kawawaki, H., Boyages, S.C., Nose, O., Ichiba, Y., Katsumata, N., Amino, N. Thyroid (1995) [Pubmed]
  37. Cloning and characterization of the 5'-flanking region of the human growth hormone-releasing hormone receptor gene. Iguchi, G., Okimura, Y., Takahashi, T., Mizuno, I., Fumoto, M., Takahashi, Y., Kaji, H., Abe, H., Chihara, K. J. Biol. Chem. (1999) [Pubmed]
  38. A growth hormone-releasing hormone-producing pancreatic islet cell tumor metastasized to the pituitary is associated with pituitary somatotroph hyperplasia and acromegaly. Sanno, N., Teramoto, A., Osamura, R.Y., Genka, S., Katakami, H., Jin, L., Lloyd, R.V., Kovacs, K. J. Clin. Endocrinol. Metab. (1997) [Pubmed]
  39. Human neutrophils express GH-N gene transcripts and the pituitary transcription factor Pit-1b. Kooijman, R., Berus, D., Malur, A., Delhase, M., Hooghe-Peters, E.L. Endocrinology (1997) [Pubmed]
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