Exogenous expression of Pit-1 in AtT-20 corticotropic cells induces endogenous growth hormone gene transcription

Kurotani, Reiko; Yoshimura, Satoshi; Iwasaki, Yoshinobu; Inoue, Keisuke; Teramoto, Akira; Osamura, R. Yoshiyuki

doi:10.1677/joe.0.1720477

Cited by 15 publications

(12 citation statements)

References 53 publications

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“…This mechanism was substantiated by a Pit-1 gene transfection experiment in the ACTH-producing cell line, AtT20 [29]. Sano et al [16] reported two cases of a corticotroph cell adenoma producing LHβ.…”

Section: Discussionmentioning

confidence: 90%

ACTH and α-Subunit are Co-expressed in Rare Human Pituitary Corticotroph Cell Adenomas Proposed to Originate from ACTH-Committed Early Pituitary Progenitor Cells

et al. 2008

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The functional differentiation of pituitary cells and adenomas follows the combination of transcription factors and co-factors in three cell lineages [growth hormone-prolactin-thyroid-stimulating hormone lineage, adrenocorticotrophic hormone (ACTH)/pro-opiomelanocortin (POMC) lineage, and follicular stimulating hormone (FSH)/luteinizing hormone (LH) lineage], which include Pit-1, GATA-2, SF-1, NeuroD1/beta2, Tpit, ERalpha, and others. Only rarely are hormones from different lineages co-expressed in the same adenoma cells. Most corticotroph cell adenomas belonging to the ACTH/POMC lineage are mono-hormonal. In our study of 89 corticotroph cell adenomas, 5 cases expressed both ACTH and alpha-subunit; these adenomas did not express any other anterior pituitary hormones or subunits. To clarify the mechanism involved, we studied the transcription factors that regulate pituitary cell differentiation. NeuroD1 and T-pit, markers of the ACTH/POMC lineage, and SF-1 and DAX-1, related to the LH/FSH cell lineage were expressed in all cases. GATA2, a synergistic factor in the gonadotroph cell lineage with SF-1, was also expressed in three of five cases. As ACTH and alpha-subunit are the earliest hormones to appear during development, we speculate that these particular adenomas are derived from committed ACTH progenitor cells. The molecular process governing functional differentiation of these adenomas requires further investigation.

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Section: Discussionmentioning

confidence: 90%

ACTH and α-Subunit are Co-expressed in Rare Human Pituitary Corticotroph Cell Adenomas Proposed to Originate from ACTH-Committed Early Pituitary Progenitor Cells

et al. 2008

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“…However, other authors have suggested that extrapituitary Pit-1 is involved, like pituitary Pit-1, in the control of GH and PRL secretion (31,32). In fact, it has been demonstrated that exogenous expression of Pit-1 in the corticotropic cell line AtT-20, which does not express GH endogenously, is capable of inducing endogenous GH mRNA and protein (39). In human mammary gland, and given that Pit-1 is expressed endogenously, it seems possible that GH and PRL may be regulated, as in the pituitary, by Pit-1 produced in the breast, and thus high concentrations of Pit-1 may induce increased concentrations of GH and PRL.…”

Section: Discussionmentioning

confidence: 99%

Pit-1 is expressed in normal and tumorous human breast and regulates GH secretion and cell proliferation

Gil¹,

Seoane²,

Blanco³

et al. 2005

eur j endocrinol

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Background: The transcription factor pituitary-1 (Pit-1) is mainly expressed in the pituitary gland, where it has critical roles in cell differentiation and as a transcriptional factor for GH and prolactin (PRL). It is also expressed in human extrapituitary tissues (placenta, lymphoid and haematopoietic tissues) and cell lines (human breast adenocarcinoma cells, MCF-7). Despite the widely suggested roles of GH and PRL in the progression of proliferative mammary disorders, Pit-1 expression in human mammary gland has not yet been reported. Objective: To evaluate the expression of Pit-1 in human breast and, using the MCF-7 cell line, to investigate whether Pit-1 overexpression regulates GH expression and increases cell proliferation. Methods: Using real-time RT-PCR, western blotting and immunohistochemistry, we evaluated the expression of Pit-1 mRNA and protein in seven normal human breasts and 14 invasive ductal mammary carcinomas. GH regulation by Pit-1 in MCF-7 cells was evaluated using RT-PCR, western blotting, ELISA and transfection assays. Cell proliferation was evaluated using bromodeoxyuridine. Results: We found expression of Pit-1 mRNA and protein in both normal and tumorous human breast. We also found that Pit-1 mRNA levels were significantly increased in breast carcinoma compared with normal breast. In MCF-7 cells, Pit-1 overexpression increased GH mRNA and protein concentrations and significantly increased cell proliferation. Conclusions: These findings indicate that Pit-1 is expressed in human breast, that it regulates endogenous human mammary GH secretion, and that it increases cell proliferation. This suggests that, depending on its level of expression, Pit-1 may be involved in normal mammary development, breast disorders, or both.

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“…Thus, other synergistic factors might similarly be involved in GH gene transcription. In our previous transfection studies of AtT-20 and αT3-1 cells, we found that only GH expression was induced by Pit-1 transfection (Kurotani et al 2002). However, in HP75 cells, although infrequent, both PRL and TSHβ mRNA were induced by Pit-1 transfection.…”

Section: Discussionmentioning

confidence: 79%

“…The Luciferase assay was carried out as previously described (Kurotani et al 2002). Briefly, COS-1 cells that were 70% confluent were transfected with pGH-Luc, adeno-Flag-Pit-1, or both vectors.…”

Section: Luciferase Assaymentioning

confidence: 99%

Induction of GH, PRL, and TSHβ mRNA by transfection of Pit-1 in a human pituitary adenoma-derived cell line

et al. 2005

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The functional development of pituitary cells depends on the expression of a combination of transcription factors and co-factors. Pituitary-specific transcription factor-1 (Pit-1) is required for the expression of growth hormone (GH), prolactin (PRL), and the thyroid-stimulating hormone beta subunit (TSH beta) and acts synergistically with the estrogen receptor (ER) and GATA-binding protein 2 (GATA-2) to induce PRL and TSH beta expression, respectively. The glycoprotein hormone alpha subunit (alpha SU) is the first hormone to be expressed during pituitary development. In addition to being expressed in follicle-stimulating hormone, luteinizing hormone (LH), and TSH cells, alpha SU is reported to co-localize with GH in pituitary cells. These findings have led to the suggestion that the expression of Pit-1 in cells of the alpha SU-based gonadotropin cell lineage might also lead to the expression of GH. In this study, we transfected HP 75 cells (derived from a human non-functioning pituitary adenoma that expressed alpha SU and LH beta) with Pit-1 by using an adenovirus FLAG-Pit-1 construct. Most of the transfected cells expressed GH mRNA, with fewer cells expressing PRL and TSH beta mRNA. The HP 75 cells expressed the genes for ER and GATA-2, thus allowing their expression of GH, PRL, and TSH beta mRNA in response to Pit-1. These results support the hypothesis that GH can be induced in cells that possess an active alpha SU gene and shed light on the basic molecular mechanism that drives the development of GH, PRL, and TSH beta expression in the alpha SU-based gonadotroph lineage.

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Exogenous expression of Pit-1 in AtT-20 corticotropic cells induces endogenous growth hormone gene transcription

Cited by 15 publications

References 53 publications

ACTH and α-Subunit are Co-expressed in Rare Human Pituitary Corticotroph Cell Adenomas Proposed to Originate from ACTH-Committed Early Pituitary Progenitor Cells

ACTH and α-Subunit are Co-expressed in Rare Human Pituitary Corticotroph Cell Adenomas Proposed to Originate from ACTH-Committed Early Pituitary Progenitor Cells

Pit-1 is expressed in normal and tumorous human breast and regulates GH secretion and cell proliferation

Induction of GH, PRL, and TSHβ mRNA by transfection of Pit-1 in a human pituitary adenoma-derived cell line

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