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Abstract:

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.

Registro:

Documento: Artículo
Título:An aryl hydrocarbon receptor agonist amplifies the mitogenic actions of estradiol in granulosa cells: Evidence of involvement of the cognate receptors
Autor:Bussmann, U.A.; Bussmann, L.E.; Barañao, J.L.
Filiación:Instituto de Biología y Medicina Experimental-CONICET, Universidad de Buenos Aires, 1428 Buenos Aires, Argentina
Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, 1428 Buenos Aires, Argentina
Vuelta de Obligado 2490, 1428 Buenos Aires, Argentina
Palabras clave: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
Año:2006
Volumen:74
Número:2
Página de inicio:417
Página de fin:426
DOI: http://dx.doi.org/10.1095/biolreprod.105.043901
Título revista:Biology of Reproduction
Título revista abreviado:Biol. Reprod.
ISSN:00063363
CODEN:BIREB
CAS:alpha naphthoflavone, 604-59-1; beta naphthoflavone, 6051-87-2; estradiol, 50-28-2; follitropin, 9002-68-0; oxygenase, 9037-29-0, 9046-59-7; alpha-naphthoflavone, 604-59-1; Aryl Hydrocarbon Hydroxylases, EC 1.14.14.1; Benzoflavones; beta-Naphthoflavone, 6051-87-2; Cytochrome P-450 CYP1A1, EC 1.14.14.1; cytochrome P-450 CYP1B1, EC 1.14.14.1; DNA, 9007-49-2; Estradiol, 50-28-2; Estrogens, Catechol; Follicle Stimulating Hormone, 9002-68-0; Mitogens; Receptors, Aryl Hydrocarbon; Receptors, Estrogen; RNA, Messenger
PDF:https://bibliotecadigital.exactas.uba.ar/download/paper/paper_00063363_v74_n2_p417_Bussmann.pdf
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00063363_v74_n2_p417_Bussmann

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Citas:

---------- APA ----------
Bussmann, U.A., Bussmann, L.E. & Barañao, J.L. (2006) . An aryl hydrocarbon receptor agonist amplifies the mitogenic actions of estradiol in granulosa cells: Evidence of involvement of the cognate receptors. Biology of Reproduction, 74(2), 417-426.
http://dx.doi.org/10.1095/biolreprod.105.043901
---------- CHICAGO ----------
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" . Biology of Reproduction 74, no. 2 (2006) : 417-426.
http://dx.doi.org/10.1095/biolreprod.105.043901
---------- MLA ----------
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" . Biology of Reproduction, vol. 74, no. 2, 2006, pp. 417-426.
http://dx.doi.org/10.1095/biolreprod.105.043901
---------- VANCOUVER ----------
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. Biol. Reprod. 2006;74(2):417-426.
http://dx.doi.org/10.1095/biolreprod.105.043901