Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 21 August 1992:
Vol. 257. no. 5073, pp. 1115 - 1118
DOI: 10.1126/science.257.5073.1115
Prev | Table of Contents | Next

Articles

A Mutation in the POU-Homeodomain of Pit-1 Responsible for Combined Pituitary Hormone Deficiency

Sally Radovick 1, Michelle Nations 2, Yuefen Du 1, LaVonne A. Berg 2, Bruce D. Weintraub 3, and Fredric E. Wondisford 2

1 Division of Endocrinology, Department of Pediatrics, Rainbow Babies and Childrens Hospital and Case Western Reserve University Medical School, Cleveland, OH 44106
2 Division of Endocrinology and Hypertension, Department of Medicine, University Hospitals of Cleveland and Case Western Reserve University Medical School, Cleveland, OH 44106
3 Molecular and Cellular Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892

Pit-1 is a pituitary-specific transcription factor responsible for pituitary development and hormone expression in mammals. Mutations in the gene encoding Pit-1 have been found in two dwarf mouse strains displaying hypoplasia of growth hormone, prolactin, and thyroid-stimulating, hormone-secreting cell types in the anterior pituitary. A point mutation in this gene was identified on one allele in a patient with combined pituitary hormone deficiency. Mutant Pit-1 binds DNA normally but acts as a dominant inhibitor of Pit-1 action in the pituitary.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Hypothalamic and pituitary development: novel insights into the aetiology.
D. Kelberman and M. T. Dattani (2007)
Eur. J. Endocrinol. 157, S3-S14
   Abstract »    Full Text »    PDF »
Involvement of the Pituitary-Specific Transcription Factor Pit-1 in Somatolactotrope Cell Growth and Death: An Approach Using Dominant-Negative Pit-1 Mutants.
I. Pellegrini, C. Roche, M.-H. Quentien, M. Ferrand, G. Gunz, S. Thirion, C. Bagnis, A. Enjalbert, and J.-L. Franc (2006)
Mol. Endocrinol. 20, 3212-3227
   Abstract »    Full Text »    PDF »
Identification and Functional Analysis of the Novel S179R POU1F1 Mutation Associated with Combined Pituitary Hormone Deficiency.
I. Miyata, S. Vallette-Kasic, A. Saveanu, M. Takeuchi, H. Yoshikawa, A. Tajima, K. Tojo, R. Reynaud, M. Gueydan, A. Enjalbert, et al. (2006)
J. Clin. Endocrinol. Metab. 91, 4981-4987
   Abstract »    Full Text »    PDF »
A Single Base Difference between Pit-1 Binding Sites at the hGH Promoter and Locus Control Region Specifies Distinct Pit-1 Conformations and Functions..
B. M. Shewchuk, Y. Ho, S. A. Liebhaber, and N. E. Cooke (2006)
Mol. Cell. Biol. 26, 6535-6546
   Abstract »    Full Text »    PDF »
Genetic Screening of Combined Pituitary Hormone Deficiency: Experience in 195 Patients.
R. Reynaud, M. Gueydan, A. Saveanu, S. Vallette-Kasic, A. Enjalbert, T. Brue, and A. Barlier (2006)
J. Clin. Endocrinol. Metab. 91, 3329-3336
   Abstract »    Full Text »    PDF »
Fishing for gene function - endocrine modelling in the zebrafish..
I M McGonnell and R C Fowkes (2006)
J. Endocrinol. 189, 425-439
   Abstract »    Full Text »    PDF »
Cell Proliferation and Vascularization in Mouse Models of Pituitary Hormone Deficiency.
R. D. Ward, B. M. Stone, L. T. Raetzman, and S. A. Camper (2006)
Mol. Endocrinol. 20, 1378-1390
   Abstract »    Full Text »    PDF »
The Role of CBP/p300 Interactions and Pit-1 Dimerization in the Pathophysiological Mechanism of Combined Pituitary Hormone Deficiency.
R. N. Cohen, T. Brue, K. Naik, C. A. Houlihan, F. E. Wondisford, and S. Radovick (2006)
J. Clin. Endocrinol. Metab. 91, 239-247
   Abstract »    Full Text »    PDF »
Repression of the prolactin promoter: a functional consequence of the heterodimerization between Pit-1 and Pit-1 {beta}.
R A Sporici, J S Hodskins, D M Locasto, L B Meszaros, A L Ferry, A M Weidner, C A Rinehart, J C Bailey, I M Mains, and S E Diamond (2005)
J. Mol. Endocrinol. 35, 317-331
   Abstract »    Full Text »    PDF »
Novel Mutations within the POU1F1 Gene Associated with Variable Combined Pituitary Hormone Deficiency.
J. P. G. Turton, R. Reynaud, A. Mehta, J. Torpiano, A. Saveanu, K. S. Woods, A. Tiulpakov, V. Zdravkovic, J. Hamilton, S. Attard-Montalto, et al. (2005)
J. Clin. Endocrinol. Metab. 90, 4762-4770
   Abstract »    Full Text »    PDF »
Pituitary Transcription Factor-1 Induces Transient Differentiation of Adult Hepatic Stem Cells into Prolactin-Producing Cells in Vivo.
E. J. Lee, T. Russell, L. Hurley, and J. L. Jameson (2005)
Mol. Endocrinol. 19, 964-971
   Abstract »    Full Text »    PDF »
Neutral sphingomyelinase 2 (smpd3) in the control of postnatal growth and development.
W. Stoffel, B. Jenke, B. Block, M. Zumbansen, and J. Koebke (2005)
PNAS 102, 4554-4559
   Abstract »    Full Text »    PDF »
Role of PROP1 in Pituitary Gland Growth.
R. D. Ward, L. T. Raetzman, H. Suh, B. M. Stone, I. O. Nasonkin, and S. A. Camper (2005)
Mol. Endocrinol. 19, 698-710
   Abstract »    Full Text »    PDF »
Genetic control of growth.
P. E Mullis (2005)
Eur. J. Endocrinol. 152, 11-31
   Abstract »    Full Text »    PDF »
Abnormal Mesenchymal Differentiation in the Superior Semicircular Canal of Brn4/Pou3f4 Knockout Mice.
S. E. Sobol, X. Teng, and E. B. Crenshaw III (2005)
Arch Otolaryngol Head Neck Surg 131, 41-45
   Abstract »    Full Text »    PDF »
A Familial Form of Congenital Hypopituitarism Due to a PROP1 Mutation in a Large Kindred: Phenotypic and in Vitro Functional Studies.
R. Reynaud, M. Chadli-Chaieb, S. Vallette-Kasic, A. Barlier, J. Sarles, I. Pellegrini-Bouiller, A. Enjalbert, L. Chaieb, and T. Brue (2004)
J. Clin. Endocrinol. Metab. 89, 5779-5786
   Abstract »    Full Text »    PDF »
Zebrafish pit1 Mutants Lack Three Pituitary Cell Types and Develop Severe Dwarfism.
G. Nica, W. Herzog, C. Sonntag, and M. Hammerschmidt (2004)
Mol. Endocrinol. 18, 1196-1209
   Abstract »    Full Text »    PDF »
Enhanced Repression by HESX1 as a Cause of Hypopituitarism and Septooptic Dysplasia.
R. N. Cohen, L. E. Cohen, D. Botero, C. Yu, A. Sagar, M. Jurkiewicz, and S. Radovick (2003)
J. Clin. Endocrinol. Metab. 88, 4832-4839
   Abstract »    Full Text »    PDF »
Human and mouse TPIT gene mutations cause early onset pituitary ACTH deficiency.
A.-M. Pulichino, S. Vallette-Kasic, C. Couture, Y. Gauthier, T. Brue, M. David, G. Malpuech, C. Deal, G. Van Vliet, M. De Vroede, et al. (2003)
Genes & Dev. 17, 711-716
   Abstract »    Full Text »    PDF »
A Novel Nonsense Mutation in the Pit-1 Gene: Evidence for a Gene Dosage Effect.
Y. Hashimoto, M. Cisternino, and L. E. Cohen (2003)
J. Clin. Endocrinol. Metab. 88, 1241-1247
   Abstract »    Full Text »    PDF »
A PIT-1 Homeodomain Mutant Blocks the Intranuclear Recruitment Of the CCAAT/Enhancer Binding Protein {alpha} Required for Prolactin Gene Transcription.
J. F. Enwright III, M. A. Kawecki-Crook, T. C. Voss, F. Schaufele, and R. N. Day (2003)
Mol. Endocrinol. 17, 209-222
   Abstract »    Full Text »    PDF »
Familial Combined Pituitary Hormone Deficiency due to a Novel Mutation R99Q in the Hot Spot Region of Prophet of Pit-1 Presenting as Constitutional Growth Delay.
T. C. Vieira, M. R. Dias da Silva, J. M. Cerutti, E. Brunner, M. Borges, L. T. Arnaldi, P. Kopp, and J. Abucham (2003)
J. Clin. Endocrinol. Metab. 88, 38-44
   Abstract »    Full Text »    PDF »
Novel Function of the Transactivation Domain of a Pituitary-specific Transcription Factor, Pit-1.
M. Kishimoto, Y. Okimura, K. Yagita, G. Iguchi, M. Fumoto, K. Iida, H. Kaji, H. Okamura, and K. Chihara (2002)
J. Biol. Chem. 277, 45141-45148
   Abstract »    Full Text »    PDF »
Pitx Factors Are Involved in Basal and Hormone-regulated Activity of the Human Prolactin Promoter.
M.-H. Quentien, I. Manfroid, D. Moncet, G. Gunz, M. Muller, M. Grino, A. Enjalbert, and I. Pellegrini (2002)
J. Biol. Chem. 277, 44408-44416
   Abstract »    Full Text »    PDF »
Molecular Basis of Combined Pituitary Hormone Deficiencies.
L. E. Cohen and S. Radovick (2002)
Endocr. Rev. 23, 431-442
   Abstract »    Full Text »    PDF »
Perspective: Genetic and Genomic Approaches in Elucidating Mechanisms of Pituitary Development.
L. E. Olson and M. G. Rosenfeld (2002)
Endocrinology 143, 2007-2011
   Abstract »    Full Text »    PDF »
Perspective: Genetic Defects in the Etiology of Congenital Hypothyroidism.
P. Kopp (2002)
Endocrinology 143, 2019-2024
   Abstract »    Full Text »    PDF »
Gonadal Determination and Adrenal Development Are Regulated by the Orphan Nuclear Receptor Steroidogenic Factor-1, in a Dose-Dependent Manner.
J. C. Achermann, G. Ozisik, M. Ito, U. A. Orun, K. Harmanci, B. Gurakan, and J. L. Jameson (2002)
J. Clin. Endocrinol. Metab. 87, 1829-1833
   Abstract »    Full Text »    PDF »
Homeobox Protein Gsh-1-Dependent Regulation of the Rat GHRH Gene Promoter.
N. Mutsuga, Y. Iwasaki, M. Morishita, A. Nomura, E. Yamamori, M. Yoshida, M. Asai, N. Ozaki, F. Kambe, H. Seo, et al. (2001)
Mol. Endocrinol. 15, 2149-2156
   Abstract »    Full Text »    PDF »
Combined Pituitary Hormone Deficiency Caused by Compound Heterozygosity for Two Novel Mutations in the POU Domain of the PIT1/POU1F1 Gene.
B. I. Hendriks-Stegeman, K. D. Augustijn, B. Bakker, P. Holthuizen, P. C. van der Vliet, and M. Jansen (2001)
J. Clin. Endocrinol. Metab. 86, 1545-1550
   Abstract »    Full Text »
Combined Pituitary Hormone Deficiency due to the F135C Human Pit-1 (Pituitary-Specific Factor 1) Gene Mutation: Functional and Structural Correlates.
S. Vallette-Kasic, I. Pellegrini-Bouiller, F. Sampieri, G. Gunz, A. Diaz, S. Radovick, A. Enjalbert, and T. Brue (2001)
Mol. Endocrinol. 15, 411-420
   Abstract »    Full Text »
POU Domain Factors in the Neuroendocrine System: Lessons from Developmental Biology Provide Insights into Human Disease.
B. Andersen and M. G. Rosenfeld (2001)
Endocr. Rev. 22, 2-35
   Abstract »    Full Text »
The hSkn-1a POU transcription factor enhances epidermal stratification by promoting keratinocyte proliferation.
J Hildesheim, U Kuhn, C. Yee, R. Foster, K. Yancey, and J. Vogel (2001)
J. Cell Sci. 114, 1913-1923
   Abstract »    PDF »
Molecular Analysis of LHX3 and PROP-1 in Pituitary Hormone Deficiency Patients with Posterior Pituitary Ectopia.
K. W. Sloop, E. C. Walvoord, A. D. Showalter, O. H. Pescovitz, and S. J. Rhodes (2000)
J. Clin. Endocrinol. Metab. 85, 2701-2708
   Abstract »    Full Text »
Contributions of Immunohistochemistry and In Situ Hybridization to the Functional Analysis of Pituitary Adenomas.
R. Y. Osamura, S. Tahara, R. Kurotani, N. Sanno, A. Matsuno, and A. Teramoto (2000)
J. Histochem. Cytochem. 48, 445-458
   Abstract »    Full Text »
Pituitary Hormone Gene Expression and Secretion in Human Growth Hormone-Releasing Hormone Transgenic Mice: Focus on Lactotroph Function.
J. P. Moore Jr., A. Cai, M. E. Hostettler, L. A. Arbogast, J. L. Voogt, and J. F. Hyde (2000)
Endocrinology 141, 81-90
   Abstract »    Full Text »    PDF »
Growth Hormone Therapy in Adults and Children.
M. L. Vance and N. Mauras (1999)
N. Engl. J. Med. 341, 1206-1216
   Full Text »    PDF »
Pituitary Hormones as Neurotrophic Signals: Update on Hypothalamic Differentiation in Genetic Models of Altered Feedback.
C. J. Phelps and D. L. Hurley (1999)
Experimental Biology and Medicine 222, 39-58
   Abstract »    Full Text »
The Rat Growth Hormone-Releasing Hormone Receptor Gene: Structure, Regulation, and Generation of Receptor Isoforms with Different Signaling Properties.
T. L. Miller, P. A. Godfrey, V. I. DeAlmeida, and K. E. Mayo (1999)
Endocrinology 140, 4152-4165
   Abstract »    Full Text »
Expression of the Members of the Ptx Family of Transcription Factors in Human Pituitary Adenomas.
I. Pellegrini-Bouiller, C. Manrique, G. Gunz, M. Grino, A. J. Zamora, D. Figarella-Branger, F. Grisoli, P. Jaquet, and A. Enjalbert (1999)
J. Clin. Endocrinol. Metab. 84, 2212-2220
   Abstract »    Full Text »
Longitudinal Hormonal and Pituitary Imaging Changes in Two Females with Combined Pituitary Hormone Deficiency due to Deletion of A301,G302 in the PROP1 Gene.
B. B. Mendonca, M. G. F. Osorio, A. C. Latronico, V. Estefan, L. S. S. Lo, and I. J. P. Arnhold (1999)
J. Clin. Endocrinol. Metab. 84, 942-945
   Abstract »    Full Text »
Defective Retinoic Acid Regulation of the Pit-1 Gene Enhancer: A Novel Mechanism of Combined Pituitary Hormone Deficiency.
L. E. Cohen, K. Zanger, T. Brue, F. E. Wondisford, and S. Radovick (1999)
Mol. Endocrinol. 13, 476-484
   Abstract »    Full Text »
The Cytogenesis and Pathogenesis of Pituitary Adenomas.
S. L. Asa and S. Ezzat (1998)
Endocr. Rev. 19, 798-827
   Abstract »    Full Text »
Pro239Ser: A Novel Recessive Mutation of the Pit-1 Gene in Seven Middle Eastern Children with Growth Hormone, Prolactin, and Thyrotropin Deficiency.
F. Pernasetti, R. D. G. Milner, A. A. Z. Al Ashwal, F. de Zegher, V. M. Chavez, M. Muller, and J. A. Martial (1998)
J. Clin. Endocrinol. Metab. 83, 2079-2083
   Abstract »    Full Text »
Advances in endocrinology.
P. E Clayton and V. Tillmann (1998)
Arch. Dis. Child. 78, 278-284
   Full Text »
Extensive Phenotypic Analysis of a Family with Growth Hormone (GH) Deficiency Caused by a Mutation in the GH-Releasing Hormone Receptor Gene.
I. Netchine, P. Talon, F. Dastot, F. Vitaux, M. Goossens, and S. Amselem (1998)
J. Clin. Endocrinol. Metab. 83, 432-436
   Abstract »    Full Text »
POU domain family values: flexibility, partnerships, and developmental codes..
A K Ryan and M G Rosenfeld (1997)
Genes & Dev. 11, 1207-1225
   PDF »
Pit-1/Growth Hormone Factor 1 Splice Variant Expression in the Rhesus Monkey Pituitary Gland and the Rhesus and Human Placenta.
J. T. Schanke, C. M. Conwell, M. Durning, J. M. Fisher, and T. G. Golos (1997)
J. Clin. Endocrinol. Metab. 82, 800-807
   Abstract »    Full Text »    PDF »
Mouse models of human disease. Part II: recent progress and future directions..
M A Bedell, D A Largaespada, N A Jenkins, and N G Copeland (1997)
Genes & Dev. 11, 11-43
   PDF »
Determinants of Thyrotrope-specific Thyrotropin beta Promoter Activation.
B. R. Haugen, M. T. McDermott, D. F. Gordon, C. L. Rupp, W. M. Wood, and E. C. Ridgway (1996)
J. Biol. Chem. 271, 385-389
   Abstract »    Full Text »    PDF »
Transcription-Factor Mutations and Disease.
D. S. Latchman (1996)
N. Engl. J. Med. 334, 28-33
   Full Text »    PDF »
The POU domain transcription factor Brn-2 is required for the determination of specific neuronal lineages in the hypothalamus of the mouse..
S Nakai, H Kawano, T Yudate, M Nishi, J Kuno, A Nagata, K Jishage, H Hamada, H Fujii, and K Kawamura (1995)
Genes & Dev. 9, 3109-3121
   Abstract »    PDF »
In Vivo Mutational Analysis of the DNA Binding Domain of the Tissue-specific Transcription Factor, Pit-1.
J. Liang, S. Moye-Rowley, and R. A. Maurer (1995)
J. Biol. Chem. 270, 25520-25525
   Abstract »    Full Text »    PDF »
Regulation of Neurite Outgrowth and SNAP-25 Gene Expression by the Brn-3a Transcription Factor.
N. D. Lakin, P. J. Morris, T. Theil, T. N. Sato, T. Möröy, M. C. Wilson, and D. S. Latchman (1995)
J. Biol. Chem. 270, 15858-15863
   Abstract »    Full Text »    PDF »
A Dopamine-responsive Domain in the N-terminal Sequence of Pit-1.
A. M. Lew and H. P. Elsholtz (1995)
J. Biol. Chem. 270, 7156-7160
   Abstract »    Full Text »    PDF »
Activation of the alpha-Internexin Promoter by the Brn-3a Transcription Factor Is Dependent on the N-terminal Region of the Protein.
V. Budhram-Mahadeo, P. J. Morris, N. D. Lakin, T. Theil, G. Y. Ching, K. A. Lillycrop, T. Möröy, R. K. H. Liem, and D. S. Latchman (1995)
J. Biol. Chem. 270, 2853-2858
   Abstract »    Full Text »    PDF »
A novel POU domain gene, zebrafish pou2: expression and roles of two alternatively spliced twin products in early development..
H Takeda, T Matsuzaki, T Oki, T Miyagawa, and H Amanuma (1994)
Genes & Dev. 8, 45-59
   Abstract »    PDF »
Identification of a novel zinc finger protein binding a conserved element critical for Pit-1-dependent growth hormone gene expression..
S M Lipkin, A M Naar, K A Kalla, R A Sack, and M G Rosenfeld (1993)
Genes & Dev. 7, 1674-1687
   Abstract »    PDF »
A tissue-specific enhancer confers Pit-1-dependent morphogen inducibility and autoregulation on the pit-1 gene..
S J Rhodes, R Chen, G E DiMattia, K M Scully, K A Kalla, S C Lin, V C Yu, and M G Rosenfeld (1993)
Genes & Dev. 7, 913-932
   Abstract »    PDF »


ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)