An aryl hydrocarbon receptor agonist amplifies the mitogenic actions of estradiol in granulosa cells: Evidence of involvement of the cognate receptors
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that, besides mediating toxic responses, may have a central role in ovarian physiology. Studying the actions of AHR ligands on granulosa cells function, we have found that beta-naphthoflavone amplifies the comitogenic act...
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| Formato: | Artículo publishedVersion |
| Lenguaje: | Inglés |
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2006
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| Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_00063363_v74_n2_p417_Bussmann |
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paperaa:paper_00063363_v74_n2_p417_Bussmann2023-06-12T16:41:15Z An aryl hydrocarbon receptor agonist amplifies the mitogenic actions of estradiol in granulosa cells: Evidence of involvement of the cognate receptors Biol. Reprod. 2006;74(2):417-426 Bussmann, U.A. Bussmann, L.E. Barañao, J.L. Estradiol Estradiol receptor Granulosa cells Ovary Toxicology alpha naphthoflavone aromatic hydrocarbon receptor beta naphthoflavone catechol estrogen cytochrome P450 1A1 cytochrome P450 1B1 estradiol estrogen receptor follitropin oxygenase animal cell animal tissue article cell proliferation controlled study DNA synthesis dose response estrogen metabolism female genetic transcription granulosa cell mitogenesis nonhuman ovary priority journal rat signal transduction Animals Aryl Hydrocarbon Hydroxylases Benzoflavones beta-Naphthoflavone Cells, Cultured Cytochrome P-450 CYP1A1 DNA Drug Synergism Estradiol Estrogens, Catechol Female Follicle Stimulating Hormone Granulosa Cells Mitogens Rats Rats, Sprague-Dawley Receptors, Aryl Hydrocarbon Receptors, Estrogen RNA, Messenger Trans-Activation (Genetics) Animalia The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that, besides mediating toxic responses, may have a central role in ovarian physiology. Studying the actions of AHR ligands on granulosa cells function, we have found that beta-naphthoflavone amplifies the comitogenic actions of FSH and 17beta-estradiol in a dose-dependent manner. This amplification was even greater in cells that overexpress the AHR and was reversed by cotreatment with the AHR antagonist alpha-naphthoflavone, suggesting that this effect is mediated by the AHR. The estrogen receptor is likewise implicated in this phenomenon, because a pure antiestrogen abolished the described synergism. However, the more traditional inhibitory AHR-estrogen receptor interaction was observed on the estrogen response element-driven transcriptional activity. On the other hand, alpha-naphthoflavone inhibited dose-dependently the mitogenic actions of FSH and 17beta-estradiol. Beta-naphthoflavone induced the expression of Cyp1a1 and Cyp1b1 transcripts, two well-characterized AHR-inducible genes that code for hydroxylases that metabolize estradiol to catecholestrogens. Nevertheless, the positive effect of beta-naphthoflavone on proliferation was not caused by increased metabolism of estradiol to catecholestrogens, because these compounds inhibited the hormonally stimulated DNA synthesis. This latter inhibition exerted by catecholestrogens suggests that these hydroxylases would play a regulatory point in granulosa cell proliferation. Our study indicates that AHR ligands modulate the proliferation of rat granulosa cells, and demonstrates for the first time that an agonist of this receptor is able to amplify the comitogenic action of classical hormones through a mechanism that might implicate a positive cross-talk between the AHR and the estrogen receptor pathways. © 2006 by the Society for the Study of Reproduction, Inc. Fil:Bussmann, U.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Barañao, J.L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2006 info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion application/pdf eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00063363_v74_n2_p417_Bussmann |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| language |
Inglés |
| orig_language_str_mv |
eng |
| topic |
Estradiol Estradiol receptor Granulosa cells Ovary Toxicology alpha naphthoflavone aromatic hydrocarbon receptor beta naphthoflavone catechol estrogen cytochrome P450 1A1 cytochrome P450 1B1 estradiol estrogen receptor follitropin oxygenase animal cell animal tissue article cell proliferation controlled study DNA synthesis dose response estrogen metabolism female genetic transcription granulosa cell mitogenesis nonhuman ovary priority journal rat signal transduction Animals Aryl Hydrocarbon Hydroxylases Benzoflavones beta-Naphthoflavone Cells, Cultured Cytochrome P-450 CYP1A1 DNA Drug Synergism Estradiol Estrogens, Catechol Female Follicle Stimulating Hormone Granulosa Cells Mitogens Rats Rats, Sprague-Dawley Receptors, Aryl Hydrocarbon Receptors, Estrogen RNA, Messenger Trans-Activation (Genetics) Animalia |
| spellingShingle |
Estradiol Estradiol receptor Granulosa cells Ovary Toxicology alpha naphthoflavone aromatic hydrocarbon receptor beta naphthoflavone catechol estrogen cytochrome P450 1A1 cytochrome P450 1B1 estradiol estrogen receptor follitropin oxygenase animal cell animal tissue article cell proliferation controlled study DNA synthesis dose response estrogen metabolism female genetic transcription granulosa cell mitogenesis nonhuman ovary priority journal rat signal transduction Animals Aryl Hydrocarbon Hydroxylases Benzoflavones beta-Naphthoflavone Cells, Cultured Cytochrome P-450 CYP1A1 DNA Drug Synergism Estradiol Estrogens, Catechol Female Follicle Stimulating Hormone Granulosa Cells Mitogens Rats Rats, Sprague-Dawley Receptors, Aryl Hydrocarbon Receptors, Estrogen RNA, Messenger Trans-Activation (Genetics) Animalia Bussmann, U.A. Bussmann, L.E. Barañao, J.L. An aryl hydrocarbon receptor agonist amplifies the mitogenic actions of estradiol in granulosa cells: Evidence of involvement of the cognate receptors |
| topic_facet |
Estradiol Estradiol receptor Granulosa cells Ovary Toxicology alpha naphthoflavone aromatic hydrocarbon receptor beta naphthoflavone catechol estrogen cytochrome P450 1A1 cytochrome P450 1B1 estradiol estrogen receptor follitropin oxygenase animal cell animal tissue article cell proliferation controlled study DNA synthesis dose response estrogen metabolism female genetic transcription granulosa cell mitogenesis nonhuman ovary priority journal rat signal transduction Animals Aryl Hydrocarbon Hydroxylases Benzoflavones beta-Naphthoflavone Cells, Cultured Cytochrome P-450 CYP1A1 DNA Drug Synergism Estradiol Estrogens, Catechol Female Follicle Stimulating Hormone Granulosa Cells Mitogens Rats Rats, Sprague-Dawley Receptors, Aryl Hydrocarbon Receptors, Estrogen RNA, Messenger Trans-Activation (Genetics) Animalia |
| description |
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that, besides mediating toxic responses, may have a central role in ovarian physiology. Studying the actions of AHR ligands on granulosa cells function, we have found that beta-naphthoflavone amplifies the comitogenic actions of FSH and 17beta-estradiol in a dose-dependent manner. This amplification was even greater in cells that overexpress the AHR and was reversed by cotreatment with the AHR antagonist alpha-naphthoflavone, suggesting that this effect is mediated by the AHR. The estrogen receptor is likewise implicated in this phenomenon, because a pure antiestrogen abolished the described synergism. However, the more traditional inhibitory AHR-estrogen receptor interaction was observed on the estrogen response element-driven transcriptional activity. On the other hand, alpha-naphthoflavone inhibited dose-dependently the mitogenic actions of FSH and 17beta-estradiol. Beta-naphthoflavone induced the expression of Cyp1a1 and Cyp1b1 transcripts, two well-characterized AHR-inducible genes that code for hydroxylases that metabolize estradiol to catecholestrogens. Nevertheless, the positive effect of beta-naphthoflavone on proliferation was not caused by increased metabolism of estradiol to catecholestrogens, because these compounds inhibited the hormonally stimulated DNA synthesis. This latter inhibition exerted by catecholestrogens suggests that these hydroxylases would play a regulatory point in granulosa cell proliferation. Our study indicates that AHR ligands modulate the proliferation of rat granulosa cells, and demonstrates for the first time that an agonist of this receptor is able to amplify the comitogenic action of classical hormones through a mechanism that might implicate a positive cross-talk between the AHR and the estrogen receptor pathways. © 2006 by the Society for the Study of Reproduction, Inc. |
| format |
Artículo Artículo publishedVersion |
| author |
Bussmann, U.A. Bussmann, L.E. Barañao, J.L. |
| author_facet |
Bussmann, U.A. Bussmann, L.E. Barañao, J.L. |
| author_sort |
Bussmann, U.A. |
| title |
An aryl hydrocarbon receptor agonist amplifies the mitogenic actions of estradiol in granulosa cells: Evidence of involvement of the cognate receptors |
| title_short |
An aryl hydrocarbon receptor agonist amplifies the mitogenic actions of estradiol in granulosa cells: Evidence of involvement of the cognate receptors |
| title_full |
An aryl hydrocarbon receptor agonist amplifies the mitogenic actions of estradiol in granulosa cells: Evidence of involvement of the cognate receptors |
| title_fullStr |
An aryl hydrocarbon receptor agonist amplifies the mitogenic actions of estradiol in granulosa cells: Evidence of involvement of the cognate receptors |
| title_full_unstemmed |
An aryl hydrocarbon receptor agonist amplifies the mitogenic actions of estradiol in granulosa cells: Evidence of involvement of the cognate receptors |
| title_sort |
aryl hydrocarbon receptor agonist amplifies the mitogenic actions of estradiol in granulosa cells: evidence of involvement of the cognate receptors |
| publishDate |
2006 |
| url |
http://hdl.handle.net/20.500.12110/paper_00063363_v74_n2_p417_Bussmann |
| work_keys_str_mv |
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| _version_ |
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