Expression of Pit-1 and related proteins in diverse human pituitary adenomas

Hoggard, Nigel; Callaghan, Kimberly D.; Levy, Andrew; Davis, Jre

doi:10.1677/jme.0.0110283

Cited by 18 publications

(14 citation statements)

References 26 publications

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“…3 Reliability from daughter information (values shown are for h 2 = 0.25). 4 Weight computed as 4 × reliability/(4 -1.5 × reliability) (values shown are for h 2 = 0.25). 5 Deregressed proofs for final score reported on the original scale, and linear scores reported on a relative scale.…”

Section: Datamentioning

confidence: 99%

“…The growth hormone factor-1/pituitary-specific transcription factor, Pit-1, a member of the POU family of homeo-domain transcription factors, activates gene expression for thyrotropin and prolactin ( PRL) and growth hormone ( GH) but also has a role in pituitary cell differentiation and proliferation (4,15). The inhibition of Pit-1 synthesis leads to a marked decrease in expression of PRL and GH and to a dramatic decrease in proliferation of cell lines producing PRL and GH ( 8 ) .…”

Section: Introductionmentioning

confidence: 99%

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Pit-1 Gene Polymorphism, Milk Yield, and Conformation Traits for Italian Holstein-Friesian Bulls

Renaville

Gengler

Vrech

et al. 1997

Journal of Dairy Science

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The growth hormone factor-1/pituitary-specific transcription factor Pit-1 is responsible for the expression of growth hormone in mammals. Mutations in Pit-1 have been found in growth hormone disorders of mice and humans. We studied the eventual association between Pit-1 polymorphism using the HinfI enzyme and the milk yield and conformation traits of 89 Italian Holstein-Friesian bulls. A strategy employing polymerase chain reaction was used to amplify a 451-bp fragment from semen DNA. Digestion of polymerase chain reaction products with HinfI revealed two alleles: allele A was not digested (451-bp fragment), and allele B was cut at one restriction site, generating two fragments of 244 and 207 bp. Three patterns were observed; frequencies were 2.2, 31.5, and 66.3% for AA, AB, and BB, respectively. Fixed and mixed linear models were fitted on daughter yield deviations for milk yields and on deregressed proofs for conformation traits. Predictions were weighted using the inverse of the estimated variance of records. The models used contained mean and gene substitution effects for Pit-1 A allele as fixed effects and random sire effect for the mixed model. The A allele was found to be superior for milk and protein yields, inferior for fat percentage, and superior for body depth, angularity, and rear leg set, which is difficult to explain. A canonical transformation revealed that Pit-1 had three actions, one linked to milk yield traits and angularity, a second linked to body depth and rear leg set, and a third linked to lower fat yields and to higher angularity. ( Key words: milk, conformation, Pit-1, restriction fragment length polymorphism) Abbreviation key: DRP = deregressed proofs, DYD = daughter yield deviations, GH = growth hormone, PCR = polymerase chain reaction, PRL = prolactin, RFLP = restriction fragment length polymorphism.

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Section: Datamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pit-1 Gene Polymorphism, Milk Yield, and Conformation Traits for Italian Holstein-Friesian Bulls

Renaville

Gengler

Vrech

et al. 1997

Journal of Dairy Science

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“…For example, the pituitary-specific transcription factor Pit-1, a member of a family of the POU-domain DNA-binding factors, has been shown to regulate growth hormone (GH), prolactin (PRL), and thyroid-stimulating hormone (TSH) cells during development and differentiation (5)(6)(7)(8)(9)(10)(11)(12). Neuro D1, a basic helix-loop-helix transcription factor, is expressed in corticotroph cells and contributes to the corticotroph-specific POMC transcription in the pituitary (13,14).…”

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confidence: 99%

Expression of GATA-2 in Human Pituitary Adenomas

et al. 2002

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Transcription factor GATA-2 contains two copies of a highly conserved zinc finger domain and plays unique roles at an early stage of hematopoietic differentiation. In the mouse pituitary gland, Pit-1-GATA-2 protein-protein interaction has been shown to lead to gene-specific actions to obtain cell-specific roles. In this study, we investigated the expression of GATA-2 and Pit-1 in human pituitary adenomas using reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical techniques. By immunohistochemical analysis, GATA-2 was detected in all of the gonadotropinsubunit (Gn-su)-positive adenomas (n ‫؍‬ 8) and in four of five thyroid-stimulating hormone (TSH)-secreting adenomas, but its incidence was low in the other types of adenomas. Pit-1 protein was detected in 4 of 5 TSH-secreting adenomas and in 10 of 10 growth hormone (GH)-secreting adenomas. By RT-PCR analysis, GATA-2 was detected in all Gn-supositive adenomas and TSH-secreting adenomas, and Pit-1 was detected in all TSH-secreting adenomas and GH-secreting adenomas. These results suggested that GATA-2 contributes to the functional expression and the differentiation of Gn-su-positive adenomas and the TSH-secreting adenomas and that the interaction between GATA-2 and Pit-1 can lead to gene-specific action and differentiation of TSH-secreting adenomas. It is further speculated that GATA-2 and transcriptional interaction with Pit-1 play roles in the functional differentiation of specific pituitary adenomas.

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“…In two ICC studies, Pit-1 was also unexpectedly observed in a limited number of ACTH-producing adenomas and clinically nonfunc tioning adenomas, although localization was found only in occasional cells [22,23]. Similarly, Hoggard et al [24] evidenced by Western blot and gel shift assay Pit-1-like immunoreactivity and DNA-binding activity not only in lactotropes and somatotropcs, but also in some nonfunc tioning adenomas. Altogether these data suggest that tumors classified as gonadotropes or null may be a more heterogeneous group, with a variety of lineages, than was previously suspected.…”

mentioning

confidence: 92%

“…A number of other reports [16][17][18][19][20][21][22][23][24] have examined human pituitary adenomas for Pit-1 gene expression. These studies, while not in total agreement, give insight into the origin of various pituitary tumors.…”

mentioning

confidence: 99%

Pit-1 Gene Expression in Human Pituitary Adenomas

Pellegrini-Bouiller

Morange-Ramos²,

Barlier³

et al. 1997

Horm Res

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The anterior pituitary-specific transcription factor Pit-1 (also known as GHF-1) was initially identified and cloned as a transactivator of the GH and PRL genes, and later as a regulator of the TSHβ gene. Analysis of Pit-1 expression during mouse embryogenesis revealed that initiation of its expression correlates both temporally and spatially with activation of its target genes. Immunocytochemical studies revealed a high expression of Pit-1 protein in the nuclei of only three cell types: somatotropes, lactotropes and thyrotropes. The importance of Pit-1 as a regulator of the anterior pituitary development has been further demonstrated by the absence of somatotropes, lactotropes and thyrotropes in the pituitary glands of Pit-1-defective mice and humans. Since Pit-1 is required for both cell phenotype and proliferation, one may ask if this transcription factor might be associated with development of pituitary tumors. Several investigators have reported Pit-1 gene expression in human pituitary adenomas. These studies, while not in total agreement, show that pituitary tumorigenesis does not seem to be associated with a gross alteration of Pit-1 gene expression in humans. Pit-1 transcripts, identical in size and sequence to those observed in normal pituitary, were described in human GH-, PRL- and TSH-secreting pituitary adenomas and in most cases the presence of Pit-1 transcripts correlated with the localization of Pit-1 protein. The biological relevance of Pit-1 expression reported in some nonfunctioning adenomas remains to be clarified. As expression of the PRL and GH genes is ultimately confined to distinct lactotropic and somatotropic populations despite the presence of Pit-1 protein in both cell types, there must be additional mechanisms that control the cell-specific activation of the PRL and GH promoters. The Pit-1β isoform, raised through alternative splicing of exon 2 of the Pit-1 gene, is a more potent inducer of GH transcription than the major Pit-1 form. This form could, at least in part, account for the cell-specific activation of the PRL and GH genes. Pit-1β was invariably found present in all the tumors expressing the Pit-1 major form, no significant difference in the Pit-1 β/Pit-1 expression ratio being observed between tumors identified as pure GH- or PRL-producing tumors. This lack of selectivity together with its low level of expression is therefore not in favor of a key role for the β-isoform in the cell type-specific expression of the GH and PRL genes in humans. The failure of somatotropes, lactotropes and thyrotropes to proliferate in Pit-1-defective mice and humans indicates that Pit-1 might be competent to activate genes required for cell proliferation or survival of the three cell types. Recent data indeed suggest that Pit-1 may directly or indirectly regulate somatotropes and lactotropes through activation of the receptors for GRF and SRIF on the one hand, and dopamine on the other hand. Such regulatory mechanisms could contribute to the differentiation of the somatomammotropic lineage in ful...

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Expression of Pit-1 and related proteins in diverse human pituitary adenomas

Cited by 18 publications

References 26 publications

Pit-1 Gene Polymorphism, Milk Yield, and Conformation Traits for Italian Holstein-Friesian Bulls

Pit-1 Gene Polymorphism, Milk Yield, and Conformation Traits for Italian Holstein-Friesian Bulls

Expression of GATA-2 in Human Pituitary Adenomas

Pit-1 Gene Expression in Human Pituitary Adenomas

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