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. 1118 - 1121
DOI: 10.1126/science.257.5073.1118
Prev | Table of Contents | Next

Articles

Mutation of the POU-Specific Domain of Pit-1 and Hypopituitarism Without Pituitary Hypoplasia

R. W. Pfäffle 1, G. E. DiMattia 2, J. S. Parks 1, M. R. Brown 1, J. M. Wit 3, M. Jansen 3, H. Van der Nat 4, J. L. Van den Brande 3, M. G. Rosenfeld 2, and H. A. Ingraham 2

1 Division of Pediatric Endocrinology, Department of Pediatrics, Emory University School of Medicine, 2040 Ridgewood Drive, Atlanta, GA 30322
2 Howard Hughes Medical Institute, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093
3 Department of Pediatrics, University of Utrecht, Utrecht, The Netherlands
4 Laboratory for Virology, National Institutes of Public Health and Environmental Protection, Bilthoven, The Netherlands

A point mutation in the POU-specific portion of the human gene that encodes the tissuespecific POU-domain transcription factor, Pit-1, results in hypopituitarism, with deficiencies of growth hormone, prolactin, and thyroid-stimulating hormone. In two unrelated Dutch families, a mutation in Pit-1 that altered an alanine in the first putative agr helix of the POU-specific domain to proline was observed. This mutation generated a protein capable of binding to DNA response elments but unable to effectively activate its known target genes, growth hormone and prolactin. The phenotype of the affected individuals suggests that the mutant Pit-1 protein is competent to initiate other programs of gene activation required for normal proliferation of somatotrope, lactotrope, and thyrotrope cell types. Thus, a mutation in the POU-specific domain of Pit-1 has a selective effect on a subset of Pit-1 target genes.


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 »
Four Novel Mutations of the LHX3 Gene Cause Combined Pituitary Hormone Deficiencies with or without Limited Neck Rotation.
R. W. Pfaeffle, J. J. Savage, C. S. Hunter, C. Palme, M. Ahlmann, P. Kumar, J. Bellone, E. Schoenau, E. Korsch, J. H. Bramswig, et al. (2007)
J. Clin. Endocrinol. Metab. 92, 1909-1919
   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 »
Genetics of growth in the normal child.
R. Pfaffle (2006)
Eur. J. Endocrinol. 155, S27-S33
   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 »
Auxological and endocrine phenotype in a population-based cohort of patients with PROP1 gene defects.
J. Lebl, J. Vosahlo, R. W Pfaeffle, H. Stobbe, J. Cerna, D. Novotna, J. Zapletalova, B. Kalvachova, V. Hana, V. Weiss, et al. (2005)
Eur. J. Endocrinol. 153, 389-396
   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 »
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 »
Role of Calcium-Calmodulin-Dependent Protein Kinase Cascade in Thyrotropin (TSH)-Releasing Hormone Induction of TSH and Prolactin Gene Expression.
K. Murao, H. Imachi, W. M. Cao, X. Yu, H. Tokumitsu, H. Inuzuka, N. C. W. Wong, M. A. Shupnik, R. Kobayashi, and T. Ishida (2004)
Endocrinology 145, 4846-4852
   Abstract »    Full Text »    PDF »
Associations of polymorphisms in the Pit-1 gene with growth and carcass traits in Angus beef cattle.
Q. Zhao, M. E. Davis, and H. C. Hines (2004)
J Anim Sci 82, 2229-2233
   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 »
Embryonic Lethality, Decreased Erythropoiesis, and Defective Octamer-Dependent Promoter Activation in Oct-1-Deficient Mice.
V. E. H. Wang, T. Schmidt, J. Chen, P. A. Sharp, and D. Tantin (2004)
Mol. Cell. Biol. 24, 1022-1032
   Abstract »    Full Text »    PDF »
RFX1 and NF-1 Associate with P Sequences of the Human Growth Hormone Locus in Pituitary Chromatin.
L. D. Norquay, X. Yang, P. Sheppard, S. Gregoire, J. G. Dodd, W. Reith, and P. A. Cattini (2003)
Mol. Endocrinol. 17, 1027-1038
   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 »
Sporadic Heterozygous Frameshift Mutation of HESX1 Causing Pituitary and Optic Nerve Hypoplasia and Combined Pituitary Hormone Deficiency in a Japanese Patient.
T. Tajima, T. Hattorri, T. Nakajima, K. Okuhara, K. Sato, S. Abe, J. Nakae, and K. Fujieda (2003)
J. Clin. Endocrinol. Metab. 88, 45-50
   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 »
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 »
Multiple Neuroendocrine Disorder in Salla Disease.
S. Grosso, R. Berardi, M. A. Farnetani, M. Margollicci, M. G. Mancini, G. Morgese, and P. Balestri (2001)
J Child Neurol 16, 775-777
   Abstract »    PDF »
New Autosomal Recessive Mutation of the TSH-{beta} Subunit Gene Causing Central Isolated Hypothyroidism.
J.-M. Vuissoz, J. Deladoey, A. Buyukgebiz, P. Cemeroglu, G. Gex, S. Gallati, and P. E. Mullis (2001)
J. Clin. Endocrinol. Metab. 86, 4468-4471
   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 »
Usefulness of Thyrotropin (TSH)-Releasing Hormone Test and Nocturnal Surge of TSH for Diagnosis of Isolated Deficit of TSH Secretion.
N. Yamakita, T. Komaki, T. Takao, T. Murai, K. Hashimoto, and K. Yasuda (2001)
J. Clin. Endocrinol. Metab. 86, 1054-1060
   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 »
Heterozygous HESX1 mutations associated with isolated congenital pituitary hypoplasia and septo-optic dysplasia.
P. Q. Thomas, M. T. Dattani, J. M. Brickman, D. McNay, G. Warne, M. Zacharin, F. Cameron, J. Hurst, K. Woods, D. Dunger, et al. (2001)
Hum. Mol. Genet. 10, 39-45
   Abstract »    Full Text »    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 »
Heritable Disorders of Pituitary Development.
(1999)
J. Clin. Endocrinol. Metab. 84, 4362-4370
   Abstract »    Full Text »
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 »
"Hot Spot" in the PROP1 Gene Responsible for Combined Pituitary Hormone Deficiency.
J. Deladoëy, C. Flück, A. Büyükgebiz, B. V. Kuhlmann, A. Eblé, P. C. Hindmarsh, W. Wu, and P. E. Mullis (1999)
J. Clin. Endocrinol. Metab. 84, 1645-1650
   Abstract »    Full Text »
Thyroid Hormone Is Essential for Pituitary Somatotropes and Lactotropes.
J. H. Stahl, S. K. Kendall, M. L. Brinkmeier, T. L. Greco, D. E. Watkins-Chow, A. Campos-Barros, R. V. Lloyd, and S. A. Camper (1999)
Endocrinology 140, 1884-1892
   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 »
Phenotypic Variability in Familial Combined Pituitary Hormone Deficiency Caused by a PROP1 Gene Mutation Resulting in the Substitution of Arg->Cys at Codon 120 (R120C).
C. Flück, J. Deladoey, K. Rutishauser, A. Eblé, U. Marti, W. Wu, and P. E. Mullis (1998)
J. Clin. Endocrinol. Metab. 83, 3727-3734
   Abstract »    Full Text »
DNase I-hypersensitive sites I and II of the human growth hormone locus control region are a major developmental activator of somatotrope gene expression.
I. M. Bennani-Baiti, S. L. Asa, D. Song, R. Iratni, S. A. Liebhaber, and N. E. Cooke (1998)
PNAS 95, 10655-10660
   Abstract »    Full Text »    PDF »
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 »
Structure of Pit-1 POU domain bound to DNA as a dimer: unexpected arrangement and flexibility..
E M Jacobson, P Li, A Leon-del-Rio, M G Rosenfeld, and A K Aggarwal (1997)
Genes & Dev. 11, 198-212
   Abstract »    PDF »
Transcription-Factor Mutations and Disease.
D. S. Latchman (1996)
N. Engl. J. Med. 334, 28-33
   Full Text »    PDF »
Anterior pituitary cells defective in the cell-autonomous factor, df, undergo cell lineage specification but not expansion.
P. Gage, M. Roller, T. Saunders, L. Scarlett, and S. Camper (1996)
Development 122, 151-160
   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 »
The POU domain: versatility in transcriptional regulation by a flexible two-in-one DNA-binding domain..
W Herr and M A Cleary (1995)
Genes & Dev. 9, 1679-1693
   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 »
The nuclear receptor steroidogenic factor 1 acts at multiple levels of the reproductive axis..
H A Ingraham, D S Lala, Y Ikeda, X Luo, W H Shen, M W Nachtigal, R Abbud, J H Nilson, and K L Parker (1994)
Genes & Dev. 8, 2302-2312
   Abstract »    PDF »
GATA factor activity is required for the trophoblast-specific transcriptional regulation of the mouse placental lactogen I gene.
Y. Ng, K. George, J. Engel, and D. Linzer (1994)
Development 120, 3257-3266
   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 »


To Advertise     Find Products

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