Paradoxical effects of tumour necrosis factor-α on rat granulosa cell DNA synthesis
Tumour necrosis factor-α (TNF-α) has been proposed as an intraovarian modulator of granulosa cell function. The effect of TNF-α on DNA synthesis in cultured rat granulosa cells was examined. Tumour necrosis factor-α stimulated thymidine incorporation when added in the presence of transforming growth...
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2002
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10313613_v14_n3-4_p133_Lanuza http://hdl.handle.net/20.500.12110/paper_10313613_v14_n3-4_p133_Lanuza |
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paper:paper_10313613_v14_n3-4_p133_Lanuza2023-06-08T16:00:35Z Paradoxical effects of tumour necrosis factor-α on rat granulosa cell DNA synthesis activin A bucladesine cell DNA ceramide cyclic AMP cytokine follitropin gonadotropin sphingomyelin phosphodiesterase thymidine transforming growth factor beta tumor necrosis factor alpha activin ceramide cyclic AMP DNA follitropin inhibin tumor necrosis factor alpha amino acid metabolism animal cell article cell culture cell differentiation cell function cell growth cell membrane permeability cell viability controlled study DNA synthesis enzyme activation female granulosa cell growth regulation hormonal regulation inhibition kinetics mitogenesis molecular mimicry nonhuman ovary follicle development ovary function paracrine signaling rat animal biosynthesis cell division comparative study cytology drug effect drug interaction metabolism Sprague Dawley rat Animalia Activins Animals Cell Division Cells, Cultured Ceramides Cyclic AMP DNA Drug Interactions Female Follicle Stimulating Hormone Granulosa Cells Inhibin-beta Subunits Rats Rats, Sprague-Dawley Tumor Necrosis Factor-alpha Tumour necrosis factor-α (TNF-α) has been proposed as an intraovarian modulator of granulosa cell function. The effect of TNF-α on DNA synthesis in cultured rat granulosa cells was examined. Tumour necrosis factor-α stimulated thymidine incorporation when added in the presence of transforming growth factor-β (TGF-β). In contrast, the co-mitogenic effect of follicle-stimulating hormone (FSH) and TGF-β was inhibited in a dose-dependent manner by TNF-α. Inhibition of FSH-dependent DNA synthesis by TNF-α was also found when cultures were co-stimulated with activin A. The inhibitory action of TNF-α on FSH-treated cultures was not associated with changes in cell viability. The inhibitory effects of TNF-α could not be solely explained by a decrease in cAMP levels, since TNF-α was also able to inhibit the stimulation by dibutyryl-cAMP and TGF-β on granulosa cell DNA synthesis. These results suggest that TNF-α regulation of granulosa cell growth is elicited either independently or downstream from gonadotrophin-induced cAMP production. The actions of TNF-α could be only partially mimicked by a cell-permeable analogue of ceramide, thus indicating that actions of this cytokine can not be fully ascribed to an activation of sphingomyelinase. Data presented here indicate that, in addition to its previously demonstrated inhibitory effects on gonadotrophin-induced cell differentiation, TNF-α may also exert a marked inhibition on hormonally stimulated immature granulosa cell proliferation. In contrast to this inhibitory action, this cytokine could amplify the mitogenic action of putative intraovarian growth regulators such as TGF-β. These observations add further support to the notion that TNF-α plays a physiological role as a paracrine modulator of follicle development and may be also relevant to the alteration of ovarian function during physiopathological processes. 2002 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10313613_v14_n3-4_p133_Lanuza http://hdl.handle.net/20.500.12110/paper_10313613_v14_n3-4_p133_Lanuza |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
activin A bucladesine cell DNA ceramide cyclic AMP cytokine follitropin gonadotropin sphingomyelin phosphodiesterase thymidine transforming growth factor beta tumor necrosis factor alpha activin ceramide cyclic AMP DNA follitropin inhibin tumor necrosis factor alpha amino acid metabolism animal cell article cell culture cell differentiation cell function cell growth cell membrane permeability cell viability controlled study DNA synthesis enzyme activation female granulosa cell growth regulation hormonal regulation inhibition kinetics mitogenesis molecular mimicry nonhuman ovary follicle development ovary function paracrine signaling rat animal biosynthesis cell division comparative study cytology drug effect drug interaction metabolism Sprague Dawley rat Animalia Activins Animals Cell Division Cells, Cultured Ceramides Cyclic AMP DNA Drug Interactions Female Follicle Stimulating Hormone Granulosa Cells Inhibin-beta Subunits Rats Rats, Sprague-Dawley Tumor Necrosis Factor-alpha |
| spellingShingle |
activin A bucladesine cell DNA ceramide cyclic AMP cytokine follitropin gonadotropin sphingomyelin phosphodiesterase thymidine transforming growth factor beta tumor necrosis factor alpha activin ceramide cyclic AMP DNA follitropin inhibin tumor necrosis factor alpha amino acid metabolism animal cell article cell culture cell differentiation cell function cell growth cell membrane permeability cell viability controlled study DNA synthesis enzyme activation female granulosa cell growth regulation hormonal regulation inhibition kinetics mitogenesis molecular mimicry nonhuman ovary follicle development ovary function paracrine signaling rat animal biosynthesis cell division comparative study cytology drug effect drug interaction metabolism Sprague Dawley rat Animalia Activins Animals Cell Division Cells, Cultured Ceramides Cyclic AMP DNA Drug Interactions Female Follicle Stimulating Hormone Granulosa Cells Inhibin-beta Subunits Rats Rats, Sprague-Dawley Tumor Necrosis Factor-alpha Paradoxical effects of tumour necrosis factor-α on rat granulosa cell DNA synthesis |
| topic_facet |
activin A bucladesine cell DNA ceramide cyclic AMP cytokine follitropin gonadotropin sphingomyelin phosphodiesterase thymidine transforming growth factor beta tumor necrosis factor alpha activin ceramide cyclic AMP DNA follitropin inhibin tumor necrosis factor alpha amino acid metabolism animal cell article cell culture cell differentiation cell function cell growth cell membrane permeability cell viability controlled study DNA synthesis enzyme activation female granulosa cell growth regulation hormonal regulation inhibition kinetics mitogenesis molecular mimicry nonhuman ovary follicle development ovary function paracrine signaling rat animal biosynthesis cell division comparative study cytology drug effect drug interaction metabolism Sprague Dawley rat Animalia Activins Animals Cell Division Cells, Cultured Ceramides Cyclic AMP DNA Drug Interactions Female Follicle Stimulating Hormone Granulosa Cells Inhibin-beta Subunits Rats Rats, Sprague-Dawley Tumor Necrosis Factor-alpha |
| description |
Tumour necrosis factor-α (TNF-α) has been proposed as an intraovarian modulator of granulosa cell function. The effect of TNF-α on DNA synthesis in cultured rat granulosa cells was examined. Tumour necrosis factor-α stimulated thymidine incorporation when added in the presence of transforming growth factor-β (TGF-β). In contrast, the co-mitogenic effect of follicle-stimulating hormone (FSH) and TGF-β was inhibited in a dose-dependent manner by TNF-α. Inhibition of FSH-dependent DNA synthesis by TNF-α was also found when cultures were co-stimulated with activin A. The inhibitory action of TNF-α on FSH-treated cultures was not associated with changes in cell viability. The inhibitory effects of TNF-α could not be solely explained by a decrease in cAMP levels, since TNF-α was also able to inhibit the stimulation by dibutyryl-cAMP and TGF-β on granulosa cell DNA synthesis. These results suggest that TNF-α regulation of granulosa cell growth is elicited either independently or downstream from gonadotrophin-induced cAMP production. The actions of TNF-α could be only partially mimicked by a cell-permeable analogue of ceramide, thus indicating that actions of this cytokine can not be fully ascribed to an activation of sphingomyelinase. Data presented here indicate that, in addition to its previously demonstrated inhibitory effects on gonadotrophin-induced cell differentiation, TNF-α may also exert a marked inhibition on hormonally stimulated immature granulosa cell proliferation. In contrast to this inhibitory action, this cytokine could amplify the mitogenic action of putative intraovarian growth regulators such as TGF-β. These observations add further support to the notion that TNF-α plays a physiological role as a paracrine modulator of follicle development and may be also relevant to the alteration of ovarian function during physiopathological processes. |
| title |
Paradoxical effects of tumour necrosis factor-α on rat granulosa cell DNA synthesis |
| title_short |
Paradoxical effects of tumour necrosis factor-α on rat granulosa cell DNA synthesis |
| title_full |
Paradoxical effects of tumour necrosis factor-α on rat granulosa cell DNA synthesis |
| title_fullStr |
Paradoxical effects of tumour necrosis factor-α on rat granulosa cell DNA synthesis |
| title_full_unstemmed |
Paradoxical effects of tumour necrosis factor-α on rat granulosa cell DNA synthesis |
| title_sort |
paradoxical effects of tumour necrosis factor-α on rat granulosa cell dna synthesis |
| publishDate |
2002 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10313613_v14_n3-4_p133_Lanuza http://hdl.handle.net/20.500.12110/paper_10313613_v14_n3-4_p133_Lanuza |
| _version_ |
1768542422638264320 |