The role of pit-1 in the regulation of the rat growth hormone-releasing hormone receptor gene transcription by glucocorticoids

Nogami, Hisashi; Hiraoka, Yoshiki; Ogasawara, Kiyomoto; Aiso, Sadakazu; Hisano, Setsuji

doi:10.1677/jme.1.01870

Cited by 6 publications

(4 citation statements)

References 37 publications

(41 reference statements)

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“…The rank of first is most highly conserved, and tenth is least highly conserved. rGHRH receptor promoter (54). In addition, this site corresponds to one of the human sites identified by Iguchi et al (44), which contributes most to Pit-1 activation of the human GHRH receptor promoter.…”

Section: Discussionmentioning

confidence: 71%

“…Further indicative of the important role Pit-1 plays in stimulating GHRH receptor expression, a mutation in a human GHRH receptor Pit-1 binding site results in decreased expression of the receptor in a patient exhibiting GH deficiency (45). Pit-1 has recently been shown to be required for glucocorticoid regulation of the rat (r) GHRH receptor (54), suggesting that cooperation between Pit-1 and other factors may lead to differential cell-specific gene regulation.…”

mentioning

confidence: 99%

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Pituitary-Specific Expression and Pit-1 Regulation of the Rat Growth Hormone-Releasing Hormone Receptor Gene

McElvaine

Korytko

Kilen

et al. 2007

Molecular Endocrinology

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The GHRH receptor is expressed in the somatotroph cell of the anterior pituitary, where it functions to mediate GHRH-stimulated GH release. To study pituitary and somatotroph cell-specific expression of this gene, a transgenic mouse model and complementary cell culture experiments were developed. The activity of the 1.6-kb proximal rat GHRH receptor promoter was examined in vivo by generating transgenic mice with the promoter directing expression of a luciferase reporter. The promoter directs tissue-specific expression; luciferase is highly expressed in the pituitary but absent from 14 other tissues. Immunocytochemistry experiments show that transgene expression is targeted to GH-expressing somatotroph cells. The transgene is 5-fold more highly expressed in males than females, and there is an increase in transgene expression leading up to the onset of puberty. The 1.6-kb promoter was further examined in cell culture experiments, which revealed that the promoter is selectively activated in pituitary cells and that promoter-reporter expression in nonpituitary cells can be enhanced by the pituitary-specific transcription factor Pit-1. EMSAs identified 10 short regions that specifically bind Pit-1 with highly variable relative affinities. The highest affinity site was previously identified and is required for Pit-1 activation of the promoter. Four additional sites contribute to Pit-1 regulation of the promoter and are important to achieving full activation of the gene. The results show that the 1.6-kb promoter is sufficient to direct tissue- and cell-specific expression in vivo and is regulated by Pit-1.

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Section: Discussionmentioning

confidence: 71%

mentioning

confidence: 99%

Pituitary-Specific Expression and Pit-1 Regulation of the Rat Growth Hormone-Releasing Hormone Receptor Gene

McElvaine

Korytko

Kilen

et al. 2007

Molecular Endocrinology

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“…In rat, two GREs along with a PIT1 binding site and an internal silencer region make up the glucocorticoid response unit. It is hypothesized that PIT1 binding to its element leads to release of an unknown factor from the silencer, allowing GR to bind to the GRE (Nogami et al, 2005).…”

Section: Regulation Of Target Genes By Pit1mentioning

confidence: 99%

Differential abilities of the chicken Pit‐1 isoforms to regulate the chicken growth hormone promoter

Mukherjee

2011

FASEB j.

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Pit1, a pituitary-specific transcription factor, regulates differentiation of cells of the PIT1 lineage in the anterior pituitary. PIT1 also regulates the synthesis of peptide hormones from these cell types, including growth hormone (GH). A founding member of the POU-homeodomain family of transcription factors, PIT1 is characterized by a serinethreonine rich N-terminal transactivation domain and a C-terminal POU-domain.Alternative forms of PIT1, differing from each other in the N-terminal domain have been reported in several species, but the functional implication of having multiple isoforms is not known. Several Pit1 isoform mRNAs exist in chickens which have not been characterized. The main aim of this study was to determine which, if any, of the chicken PIT1 isoforms regulated the chicken Gh (cGh) promoter. PIT1β2, a novel isoform of chicken PIT1 was discovered, and known and novel isoforms (PIT1α, PIT1β1, PIT1β2 and PIT1γ) were characterized. A luciferase reporter construct containing 1775bp of the cGh promoter driving expression of firefly luciferase was used to determine the ability of the isoforms to regulate the target gene promoter activity in chicken LMH cells. We showed that three of the isoforms, PIT1α, PIT1β1 and PIT1β2, expressed from recombinant plasmids, regulated the cGh promoter, while PIT1γ did not. All the isoforms localized to the nucleus in both non-pituitary and pituitary cells. Results from gel-shift assays show that PIT1γ did not bind the proximal PIT1-binding site of the cGh promoter as well as the other isoforms, suggesting a possible mechanism behind the inactivity. Our result did not suggest a negative regulatory role for this isoform. In contrast, we found a functional advantage for having multiple isoforms. PIT1β1, the isoform that activated the promoter most strongly, when co-transfected with other activating isoforms, such as PIT1α and PIT1β2, induced significantly higher level of activation than one isoform alone. Whether this increased activation required, or was facilitated by, heterodimerization of two isoforms is not known. Nevertheless, identification of isoforms © Copyright by Malini Mukherjee 2011 work that much harder to never fail. Dear daidamoni, my brother, what would I do without you?! Not only do we share our parents, we share our each and every happiness and loss, sadness and elation, together. Sarmila, thank you for joining our family and making our house a home again. Sonali, why didn't I get to know you better years ago? If I had, I am certain I would have not made many of the mistakes I did in my graduate career. Anyway, now that you are here, you are not going anywhere. Thank you! Susmita, I would never have reached this milestone without your help! How can I thank you enough? Thank you for being you; keep smiling, always! I would also like to thank a few dear friends and cousins, many of whom have already been or are currently pursuing the same degree in me. Thank you Tannistha, Sangeeta, Pragati, Dan, Oli, Veena, Piu. Thank you all for all your support. And l...

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“…However, if these GREs are combined, they exert stronger GRE activity. The combined GRE mediates glucocorticoid action on GHRH-gene expression in the presence of pit-1 [81]. The molecular mechanisms of the pit-1-dependent and glucocorticoid-induced GHRH-receptor gene transcription have yet to be elucidated.…”

Section: Molecular Mechanism Of Glucocorticoid-induction Of Ghrh-recementioning

confidence: 99%

Functional maturation of growth hormone cells in the anterior pituitary gland of the fetus

Nogami

Hisano

2008

Growth Hormone & IGF Research

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Recent studies have disclosed the molecular mechanisms responsible for the phenotype determination of the anterior pituitary cell types. However, as far as growth hormone (GH) cells are concerned, particular extra-cellular cues are required for the initiation of GH and GH-releasing hormone (GHRH)-receptor gene production in addition to the expression of the cell type specific transcription factor, pit-1. The glucocorticoids play a principal role in the functional maturation of nascent GH cells in the fetal pituitary glands in rodents, inducing GH and GHRH-receptor gene expression, and establish the GH secretory system regulated by the brain in late gestation. Research supporting this role for glucocorticoid in the development of GH cells is discussed.

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The role of pit-1 in the regulation of the rat growth hormone-releasing hormone receptor gene transcription by glucocorticoids

Cited by 6 publications

References 37 publications

Pituitary-Specific Expression and Pit-1 Regulation of the Rat Growth Hormone-Releasing Hormone Receptor Gene

Pituitary-Specific Expression and Pit-1 Regulation of the Rat Growth Hormone-Releasing Hormone Receptor Gene

Differential abilities of the chicken Pit‐1 isoforms to regulate the chicken growth hormone promoter

Functional maturation of growth hormone cells in the anterior pituitary gland of the fetus

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