Transforming growth factor-alpha stimulates proliferation of mammotrophs and corticotrophs in the mouse pituitary

Oomizu, Souichi; Honda, Junichi; Tanaka, Sakae; Kakeya, Tomoshi; Masui, Tohru; Takahashi, Sumio

doi:10.1677/joe.0.1650493

Cited by 37 publications

(36 citation statements)

References 43 publications

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“…However, physiological growth factors which are involved in steroid hormone-induced proliferation of the stromal cells remains to be determined. Interestingly, in a study of pituitary growth, we found that TGF-α is a mediator of estrogen-induced proliferation of mammotrophs, since treatment of mouse pituitary cells with antisense TGF-α oligodeoxynucleotide or anti-TGF-α antibodies inhibited estrogen-induced proliferation of mammotrophs (Oomizu et al, 2000;Takahashi et al, 2002;Sharma et al, 2003). These results altogether suggest that estrogen-induced growth of various tissues is controlled by a common mechanism of an autocrine or paracrine action of growth factors.…”

Section: Discussionmentioning

confidence: 86%

Epidermal Growth Factor and Transforming Growth Factor-α Stimulate the Proliferation of Mouse Uterine Stromal Cells

et al. 2003

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-Growth factors produced in the uterine endometrium are considered to be involved in the proliferation of the mouse uterine stromal cells induced by estradiol-17 β (E 2 ) and progesterone (P). The effect of epidermal growth factor (EGF) and transforming growth factor-α (TGF-α ), one of EGF-related growth factors, on the proliferation of mouse uterine stromal cells was studied in a serum-free culture. The growth of the uterine stromal cells was measured by MTT assay. EGF was found to increase the number of uterine stromal cells in a dose-dependent manner. The DNA-replicating cells were investigated using the immunocytochemical detection of bromodeoxyuridine (BrdU)-labeled cells. EGF and TGF-α increased the percentage of BrdU-labeled cells in a dose-dependent manner. Administration of the combination of E 2 (10 -9 M) and P (10 -7 M) for 2 days increased the percentage of BrdU-labeled cells 2.3-fold. The stimulatory effect of EGF, TGF-α and the combination of E 2 and P on DNA replication in the uterine stromal cells was repressed by RG-13022 (10 -5 M, the inhibitor of the EGF receptor tyrosine kinase). RT-PCR analysis of EGF-receptor-, TGF-α -, and EGF-mRNA was carried out in the cultured uterine stromal cells, and revealed the expression of those mRNAs. These data supported the hypothesis that uterine endometrial stromal growth induced by sex steroids required the EGF family of ligands such as EGF and TGF-α , both produced in the stromal cells, acting for DNA synthesis through EGF receptors.

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Section: Discussionmentioning

confidence: 86%

Epidermal Growth Factor and Transforming Growth Factor-α Stimulate the Proliferation of Mouse Uterine Stromal Cells

et al. 2003

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“…Cyclin D1 overexpression that is the functional characteristic of nuclear EGFR is not featured in human corticotrophinomas (10). Nevertheless, nuclear EGFR was detected by immunofluorescence in this pituitary tumor subtype (50). Nuclear EGFR deubiquitination by nuclearly-located USP8 mutants may regulate the nuclear function of EGFR.…”

Section: The CD Usp8 Mutants Affect Egfr Downregulation and Acth Syntmentioning

confidence: 88%

“…In primary cultures of male mouse anterior pituitaries, EGF treatment enhanced BrdU uptake in ACTH-(as well as in PRL-) immunopositive cells, but not in other pituitary cell subpopulations (37). The EGFR inhibitor RG-13022 decreased the percentage of BrdU labeled cells immunoreactive for ACTH (and PRL), providing functional evidence for the presence of active receptors on corticotroph (and lactotroph) populations (50).…”

Section: Egfr and Corticotroph Functionmentioning

confidence: 94%

Decoding the genetic basis of Cushing's disease: USP8 in the spotlight

Theodoropoulou

Reincke

Faßnacht

et al. 2015

European Journal of Endocrinology

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Cushing's disease (CD) arises from pituitary-dependent glucocorticoid excess due to an ACTH-secreting corticotroph tumor. Genetic hits in oncogenes and tumor suppressor genes that afflict other pituitary tumor subtypes are not found in corticotrophinomas. Recently, a somatic mutational hotspot was found in up to half of corticotrophinomas in the USP8 gene that encodes a protein that impairs the downregulation of the epidermal growth factor receptor (EGFR) and enables its constitutive signaling. EGF is an important regulator of corticotroph function and its receptor is highly expressed in Cushing's pituitary tumors, where it leads to increased ACTH synthesis in vitro and in vivo. The mutational hotspot found in corticotrophinomas hyper-activates USP8, enabling it to rescue EGFR from lysosomal degradation and ensure its stimulatory signaling. This review presents new developments in the study of the genetics of CD and focuses on the USP8-EGFR system as trigger and target of corticotroph tumorigenesis.

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“…It is well known that PRL cells have the ability to replicate DNA and to divide in rat and mouse pituitary glands in vivo and in vitro in response to estrogen and various growth factors (Takahashi et al ., 1984;Oishi et al ., 1993;Oomizu et al ., 2000). In contrast, it is evident from the present study that PRL cells of GH3 cells are unable to replicate DNA molecules.…”

Section: Discussionmentioning

confidence: 99%

“…The highest mitotic activity of PRL cells is observed at estrus in the female rat pituitary (Takahashi et al ., 1984;Oishi et al ., 1993). As estrogen treatment stimulates the proliferation of PRL cells (Lloyd et al ., 1975;Takahashi and Kawashima, 1987;Oomizu et al ., 2000), the high proliferating activity of PRL cells is caused by the increase in estrogen secretion during the proestrous and estrous days. Thus, it is evident that PRL cells are generated from preexisting PRL cells through mitosis under estrogenic stimulation (self-duplication) in vivo .…”

Section: Introductionmentioning

confidence: 99%

Induction of mammotroph development by a combination of epidermal growth factor, insulin, and estradiol-17β in rat pituitary tumor GH3 cells

Kakeya

Tanaka

Takahashi³

2002

Zoological Science

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-Several reports have indicated that prolactin-secreting cells (PRL cells) are generated from growth hormone-secreting cells (GH cells). We have shown that treatment with a combination of epidermal growth factor (EGF), insulin, and estradiol-17 β (E 2 ) induces the appearance of PRL cells in pituitary tumor GH3 cells. The aim of the present study was to clarify the involvement of mitosis in the cytogenesis of PRL cells in rat pituitary and GH3 cells. The effects of the treatment with EGF, insulin and E 2 on DNAreplication were studied by detecting the uptake of bromodeoxyuridine (BrdU) into the nucleus. In cultured rat pituitary cells, BrdU-labeled PRL cells were observed irrespective of the hormone treatment. In GH3 cells, BrdU-labeled GH cells and mammosomatotrophs (MS cells) were detected; BrdU-labeled PRL cells were not detected, however, when GH3 cells were treated with BrdU for 3 hr and then immediately examined for BrdU-labeling. BrdU-labeled PRL cells were found only when GH3 cells treated with BrdU were allowed to grow for another 3 days. This finding suggests that during the additional 3-day culture, BrdUlabeled PRL cells were generated from BrdU-labeled cells other than PRL cells. These results indicate that PRL cells are transdifferentiated from GH cells or MS cells in GH3 cells by a combined treatment with EGF, insulin and E 2 , while PRL cells in rat pituitaries are able to proliferate in response to the hormone treatment. Thus, there may be two pathways for cytogenesis of PRL cells: the transdifferentiation of GH cells or MS cells, and a self-duplication of PRL cells.

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Transforming growth factor-alpha stimulates proliferation of mammotrophs and corticotrophs in the mouse pituitary

Cited by 37 publications

References 43 publications

Epidermal Growth Factor and Transforming Growth Factor-α Stimulate the Proliferation of Mouse Uterine Stromal Cells

Epidermal Growth Factor and Transforming Growth Factor-α Stimulate the Proliferation of Mouse Uterine Stromal Cells

Decoding the genetic basis of Cushing's disease: USP8 in the spotlight

Induction of mammotroph development by a combination of epidermal growth factor, insulin, and estradiol-17β in rat pituitary tumor GH3 cells

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