Disease relevance of Pou1f1

• Pituitary lineage determination by the Prophet of Pit-1 homeodomain factor defective in Ames dwarfism [1].
• Mutations that cause pituitary dwarfism in the mouse reside in the gene encoding the transcription factor growth hormone factor 1 (GHF1 or pit1) [2].
• Immortalized cell lines derived from a transgenic pituitary tumor maintain the characteristics of the somato/lactotropic progenitor in that they express GHF-1 mRNA and protein yet fail to activate GH or PRL transcription [3].
• Earlier studies have shown that a stretch of nine residues (position 550 to 558) in the fourth extracellular domain of Pit1 is crucial for GALV entry and that an acidic residue at position 550 is indispensable [4].
• Therefore, the presence of a Pit1 loop 4-specific sequence is sufficient to confer receptor function for the mammalian retrovirus GALV on the fungal phosphate transporter Pho-4 [5].

High impact information on Pou1f1

• The relationship between expression of the pituitary-specific transcription factor, GHF-1, and activation of the growth hormone and prolactin genes during mouse anterior pituitary development was investigated [6].
• The spatial and temporal correlation between the appearance of GHF-1 protein and growth hormone gene activation suggests that GHF-1 is responsible for this very last step in the specialization of somatotrophic cells [6].
• Growth hormone (GH) expression in pituitary-derived cells has been attributed to the presence of a positive trans-activator, GHF-1, which binds to two sites on the GH promoter [7].
• Rather, extinction of GH expression in fibroblast x pituitary hybrids was accompanied by loss of GHF-1 protein and mRNA expression, suggesting that extinction occurs by repression of this trans-activator [7].
• Extinction of growth hormone expression in somatic cell hybrids involves repression of the specific trans-activator GHF-1 [7].

Chemical compound and disease context of Pou1f1

• However, each case exhibited multifocal, microscopic lactotroph adenomas with strong nuclear immunoreactivity for estrogen receptors and Pit-1 transcription factor [8].
• The X-ray induction of micronuclei and structural chromosomal aberrations was studied in bone-marrow cells of normal and dwarf (dw) mice in combination with thyroxine and/or prolactin treatment or otherwise [9].
• Upon induction with isopropyl beta-D-thiogalactopyranoside, Pit-1 was expressed and accumulated as inclusion bodies in E. coli [10].

Biological context of Pou1f1

• Pitx1 mutants have a mild pituitary phenotype, but Pitx2 is necessary for the development of Rathke's pouch, expression of essential transcription factors in gonadotropes, and expansion of the Pit1 lineage [11].
• Pit1-deficient mice first exhibit pituitary hypoplasia after birth, primarily caused by reduced cell proliferation, although there is some apoptosis [12].
• These data suggest that, despite similarities in promoter structure, changes in the relative importance of conserved transcription factor binding sites cause species-dependent differences in Pit1 promoter function, which allow Sp1-related proteins to play a particularly important role in human [13].
• The Snell dwarf mouse (Pit1dw-J homozygote) has a mutation in the Pit1 gene that prevents the normal formation of the anterior pituitary [14].
• We conclude that the Pit1 mutation may result in physiological homeostasis that favors longevity, and that the Snell dwarf mutant conforms to the nematode longevity paradigm [15].

Anatomical context of Pou1f1

• In contrast to the signal pattern seen in TtT-97, only two bands were seen in alphaSUnull tumors, which were similar in size to those in alphaTSH cells, a thyrotropic cell line that lacks TSHbeta-subunit expression and Pit1 protein [16].
• Pit-1 is a pituitary-specific transcription factor with protein expression limited to thyrotrope, somatotrope, and lactotrope cells of the anterior pituitary gland [17].
• Thus, compared with normal mice of the same strain, the A12 deficit is more severe in Snell (dw/dw) than in Ames (df/df) dwarf hypothalamus (48% of DF/?), as previously reported, and develops as a decline from the population present at 7 d rather than first increasing [18].
• These dwarf mice (dw and dwJ) are deficient in growth hormone (GH) and prolactin (PRL) synthesis and exhibit pituitary hypoplasia, suggesting a stem cell defect [2].
• However, bone marrow cellularity in thyroxine-treated dw/dw mice was comparable to that in control animals, and both the frequency and absolute number of B lineage cells had increased to normal or even above normal [19].

Associations of Pou1f1 with chemical compounds

• The abnormalities observed in the Pit1dw-J homozygote mouse seem to be caused by both direct and indirect effects of the deficiency of TSH (or T4), PRL, or GH rather than by a direct effect of the deletion of Pit1 [14].
• Immunocytochemical effects of thyroxine stimulation on the adenohypophysis of dwarf (dw) mutant mice [20].
• Furthermore, some FSH and LH cells became Pit-1 positive, and co-localized with PRL at 5-10 days [21].
• For example, the K216E mutant has defective retinoic acid signaling on the Pit-1 gene enhancer [22].
• We conclude therefore that long-term E2 replacement rescues the dysfunction of somatotropes in ArKO/OVX mice through increases in expression of GH, GHRH-R, and Pit-1 in the pituitary somatotropes, whereas the level of androgen in this oestrogen-deficient female mouse does not significantly influence the function of somatotropes [23].

Physical interactions of Pou1f1

• The pituitary-specific transcription factor Pit-1 is present in thyrotropes and interacts with three cis-acting elements in the functionally important region of the TSH beta promoter [24].

Regulatory relationships of Pou1f1

• Pit-1 and GATA-2 interact and functionally cooperate to activate the thyrotropin beta-subunit promoter [25].
• Both basal and GHRH-induced salivary GH expression appear to be independent of Pit-1 [26].
• (1) In the hippocampus, hippocalcin immunoreactivity was found in the cell body and dendrites of pyramidal neurons of the normal controls and dw mice, although the intensity of immunoreactivity in the dw mice was lower [27].

Other interactions of Pou1f1

• Several lines of evidence demonstrate that df acts earlier in the differentiation pathway than Pit1 [28].
• Thus, the rate of transcription and/or the stability of SS mRNA are affected by the dw mutation [29].
• A thyrotrope-specific variant of Pit-1 transactivates the thyrotropin beta promoter [24].
• Pit-1 mRNA was not detected in dwarf mice, was 2.9% of normal in lit/lit (p < 0.005) mice, and increased to 200% in GHRH-excess mice (p < 0.05) [30].
• The cell extracts also showed an increased abundance of both Zn-16 and Pit-1 mRNAs when compared with whole pituitary extracts [30].

Analytical, diagnostic and therapeutic context of Pou1f1

• However, western blot analysis revealed a protein band in the alphaSUnull tumors consistent with Pit1, while this signal was absent in alphaTSH cells [16].
• The effects of dietary thyroxine on the immunoreactivity of cells in the pars distalis of the adenohypophysis in dwarf (dw/dw) mice were determined by ultrastructural immunocytochemistry [20].
• The presence of Pit-1 transcript in the kidney was also assessed by RT-PCR methods [31].
• Southern blot analysis of genomic DNA reveals that the Pit-1 gene is rearranged in C3H/HeJ-dwJ/dw mice but not in coisogenic +/+ animals, providing molecular evidence that a lesion in the Pit-1 gene results in the Snell dwarf phenotype [32].
• Luciferase reporter analysis and electrophoretic mobility shift assays show that Pit-1 activates the human mimecan promoter through Pit-1 response element sites [33].

References