Follicle-Stimulating Hormone Induces Terminal Differentiation in a Predifferentiated Rat Granulosa Cell Line (ROG)

Li, R.

doi:10.1210/en.138.7.2648

Cited by 12 publications

(9 citation statements)

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“…The exposure to FSH does not result in an equal effect among follicles, since selective growth factor expression significantly amplifies FSHR gene expression and presumably FSH action in a subset of follicles. In a previous study, it was reported that activin supported granulosa cell survival and cell proliferation, and maintained the functional FSHR in the absence of FSH throughout long-term culture [28]. In our cultured cells, activin alone induced FSHR mRNA and protein expression, whereas the IGF-I effect on FSHR mRNA was dependent on the presence of FSH.…”

Section: Discussionsupporting

confidence: 52%

A Role of Insulin-Like Growth Factor I for Follicle-Stimulating Hormone Receptor Expression in Rat Granulosa Cells1

Minegishi

Hirakawa

Kishi

et al. 2000

Biology of Reproduction

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The present study was undertaken to identify the mechanisms underlying the effect of insulin-like growth factor I (IGF-I) on FSH receptor (FSHR) in rat granulosa cells. Treatment with FSH produced a substantial increase in FSHR mRNA level, as was expected, while concurrent treatment with increasing concentrations of IGF-I brought about dose-dependent increases in FSH-induced FSHR mRNA, with a maximal response 2.8-fold greater than that induced by FSH alone. IGF-I, either alone or in combination with FSH, did not affect intracellular cAMP levels, whereas it enhanced the effect of 8-bromo (Br)-cAMP on FSHR mRNA production. Taken together, these findings suggest that the ability of IGF-I to enhance FSH action concerning the induction of FSHR is exerted at sites distal to cAMP generation. We then investigated whether the effect of IGF-I and FSH on FSHR mRNA levels was the result of increased transcription and/or altered mRNA stability. The rates of FSHR mRNA gene transcription, assessed by nuclear run-on transcription assay, were not increased by the addition of IGF-I. On the other hand, the decay curves for the 2. 4-kilobase (kb) FSHR mRNA transcript in primary granulosa cells significantly altered the slope of the FSHR mRNA decay curve in the presence of IGF-I and increased the half-life of the FSHR mRNA transcript. These data suggest a possible role for changes in FSHR mRNA stability in the IGF-I-induced regulation of FSHR in rat granulosa cells. Treatment with activin produced a substantial increase in FSHR mRNA level, as was expected, and concurrent treatment with IGF-I did not affect activin-induced FSHR mRNA. Our data suggest that the IGF-I effect on FSHR expression is related to cAMP production induced by FSH and may maintain FSHR mRNA level because of prolonged FSHR mRNA stability.

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Section: Discussionsupporting

confidence: 52%

A Role of Insulin-Like Growth Factor I for Follicle-Stimulating Hormone Receptor Expression in Rat Granulosa Cells1

Minegishi

Hirakawa

Kishi

et al. 2000

Biology of Reproduction

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“…Additionally, the genes for the membrane receptors for the gonadotropins FSH and LH are strongly down-regulated in the cell lines, so that gonadotropins are not able to exert effects on the GK cell lines. This finding was not unexpected, as there are only two reports in the literature indicating that FSH receptor expression was conserved in established granulosa cell lines [14,25]. Apparently, immortalized granulosa cell lines like those described by us tend to down-regulate FSH receptor expression, thus removing an important external signal that could interfere with permanent growth and induce differentiation.…”

Section: Discussionsupporting

confidence: 60%

“…Main indicators used are an increase in progesterone production and the downregulation of estradiol synthesis. In order to develop experimental systems better suited for the study of granulosa cell functions, numerous granulosa cell lines have been established from several species, mostly by immortalization of primary granulosa cells by viral oncogenes or stimulation of granulosa cell growth by mitogens [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25]. The majority of these cell lines represent luteinizing granulosa cells, demonstrating that the process of immortalization does not prevent the spontaneous luteinization of granulosa cells in culture.…”

Section: Introductionmentioning

confidence: 99%

“…One cell line conserving FSH receptor expression and the stimulation of estradiol production by FSH has been described [14]; two other lines show induction of P450 aromatase (P450 arom ) expression by cAMP [19] or constitutive P450 arom expression [23]. Recently, one cell line has been described that responds to FSH by an irreversible stop of proliferation followed by cell differentiation [25]. This cell line apparently represents early granulosa cells, but the cells do not express P450 arom after FSH induction.…”

Section: Introductionmentioning

confidence: 99%

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Expression of Granulosa Cell-Specific Genes and Induction of Apoptosis in Conditionally Immortalized Granulosa Cell Lines Established from H-2Kb-tsA58 Transgenic Mice

Walther¹,

Einspanier

Jansen³

1999

Biology of Reproduction

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Granulosa cell lines have been established from H-2Kb-tsA58 transgenic mice. Using immunocytochemistry, significant amounts of insulin-like growth factor-I (IGF-I) were found in all cell lines investigated, whereas estrogen and progesterone receptor expression could be detected in only some of the lines. All cell lines showed low basal production of the gonadal steroids estradiol and progesterone. The genes for the ovarian paracrine regulators IGF-I and basic fibroblast growth factor were expressed, as well as the genes for anti-Müllerian hormone and for the P450 side-chain cleavage enzyme (P450scc). Expression of P450scc could be shown to be up-regulated in the cell lines under conditions mimicking the hormonal environment of the luteinizing granulosa cells in vivo. Inactivation of the temperature-sensitive SV40 T antigen by a shift of the cell lines to the nonpermissive temperature of 39.5 degrees C led to massive induction of apoptosis in several cell lines. These cell lines will allow a detailed study of the mechanisms regulating the expression of granulosa cell-specific functions, as well as the induction of granulosa cell apoptosis.

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“…Twice weekly i.p. treatment of established SNU-16 xenografts (150 -200 mm 3 tumor volume) with RAV12 at 10 mg/kg completely suppressed tumor growth over the initial 15 days of treatment and resulted in an overall decrease in tumor growth of 66% at the end of the study (Fig. 5E).…”

Section: Rav12 Inhibitstumor Growth In Multiple Gastrointestinal Xenomentioning

confidence: 89%

The glycotope-specific RAV12 monoclonal antibody induces oncosis in vitro and has antitumor activity against gastrointestinal adenocarcinoma tumor xenografts in vivo

Loo¹,

Pryer²,

Young³

et al. 2007

Molecular Cancer Therapeutics

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RAV12 is a chimeric antibody that recognizes an N-linked carbohydrate antigen (RAAG12) strongly expressed on multiple solid organ cancers. More than 90% of tumors of colorectal, gastric, and pancreatic origin express RAAG12, and a majority of these tumors exhibit uniform RAAG12 expression. RAV12 exhibits potent cytotoxic activity in vitro against COLO 205 colon tumor cells via an oncotic cell death mechanism. RAV12-treated COLO 205 cells undergo morphologic changes consistent with oncosis, including cytoskeletal rearrangement, rapid plasma membrane swelling, and cell lysis. RAV12 inhibited the growth of RAAG12-expressing gastrointestinal tumor xenografts in athymic mice. In the case of SNU-16 tumor cells, twice weekly treatment of established s.c. tumors with 10 mg/kg RAV12 caused a f70% suppression of tumor growth at the end of the study. This preclinical data has led to the initiation of a phase I/IIA clinical study of RAV12 in patients with metastatic or recurrent adenocarcinoma. [Mol Cancer Ther 2007;6(3):856 -65]

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Follicle-Stimulating Hormone Induces Terminal Differentiation in a Predifferentiated Rat Granulosa Cell Line (ROG)

Cited by 12 publications

References 0 publications

A Role of Insulin-Like Growth Factor I for Follicle-Stimulating Hormone Receptor Expression in Rat Granulosa Cells1

A Role of Insulin-Like Growth Factor I for Follicle-Stimulating Hormone Receptor Expression in Rat Granulosa Cells1

Expression of Granulosa Cell-Specific Genes and Induction of Apoptosis in Conditionally Immortalized Granulosa Cell Lines Established from H-2Kb-tsA58 Transgenic Mice

The glycotope-specific RAV12 monoclonal antibody induces oncosis in vitro and has antitumor activity against gastrointestinal adenocarcinoma tumor xenografts in vivo

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