Estrogen action via the cAMP signaling pathway: stimulation of adenylate cyclase and cAMP-regulated gene transcription.
Open accessAbstract
Estrogenic hormones, believed to exert most of their effects via the direct interaction of their receptors with chromatin, are found to increase cAMP in target breast cancer and uterine cells in culture and in the intact uterus in vivo. Increases in intracellular cAMP are evoked by very low concentrations of estradiol (half maximal at 10 pM) and by other physiologically active estrogens and antiestrogens, but not by an inactive estrogen stereoisomer. These increases in cAMP result from enhanced membrane adenylate cyclase activity by a mechanism that does not involve genomic actions of the hormones (are not blocked by inhibitors of RNA and protein synthesis). The estrogen-stimulated levels of cAMP are sufficient to activate transcription from cAMP response element-containing genes and reporter plasmid constructs. Our findings document a nongenomic action of estrogenic hormones that involves the activation of an important second-messenger signaling system and suggest that estrogen regulation of cAMP may provide an additional mechanism by which this steroid hormone can alter the expression of genes.
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Estrogen activates PI3K to recruit AKT/PKB to the cell membrane in mammals via a mechanism independent of the genomic actions of hormones.
“For example, estrogen activates phosphoinositide 3 kinase (PI3K) to recruit protein kinase B (AKT/PKB) to the cell membrane in mammals via a mechanism independent of the genomic actions of hormones [14].”
From G protein-coupled receptors function as cell membrane receptors for the steroid hormone 20-hydroxyecdysone (2020) · cites this paper as [14]
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Cites
Identification of a cyclic-AMP-responsive element within the rat somatostatin gene.
Montminy, M., Sevarino, K. A., Wagner, J. A., Mandel, G., & Goodman, R. H. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.18.6682 · Cited by 1,385 · see citing works
Biochemical actions of hormones
(1987) · General and Comparative Endocrinology · doi:10.1016/0016-6480(87)90137-7 · Cited by 576 · see citing works
Aronica, S. M., & Katzenellenbogen, B. S. (1993) · Molecular Endocrinology · doi:10.1210/mend.7.6.7689695 · Cited by 455 · see citing works
Self-citationGoff, P. L., Montano, M. M., Schodin, D. J., & Katzenellenbogen, B. S. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)41801-1 · Cited by 452 · see citing works
Self-citationAli, S., METZGER, D., Bornert, J., & Chambon, P. (1993) · The EMBO Journal · doi:10.1002/j.1460-2075.1993.tb05756.x · Cited by 441 · see citing works
Adenosine 3',5'-monophosphate in rat uterus: acute elevation by estrogen.
Szego, C. M., & Davis, J. S. (1967) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.58.4.1711 · Cited by 406 · see citing works
Lohse, M. J., Benovic, J. L., Caron, M. G., et al. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)39754-6 · Cited by 404 · see citing works
TRANSCRIPTION ACTIVATION BY ESTROGEN AND PROGESTERONE RECEPTORS
Gronemeyer, H. (1991) · Annual Review of Genetics · doi:10.1146/annurev.ge.25.120191.000513 · Cited by 371 · see citing works
Dynamics of Steroid Hormone Receptor Action
Katzenellenbogen, B. S. (1980) · Annual Review of Physiology · doi:10.1146/annurev.ph.42.030180.000313 · Cited by 346 · see citing works
Self-citationEstrogen-responsive element of the human pS2 gene is an imperfectly palindromic sequence.
Berry, M., Nunez, A. M., & Chambon, P. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.4.1218 · Cited by 336 · see citing works
Ignar-Trowbridge, D. M., Teng, C. T., Ross, K. A., Parker, M. G., Korach, K. S., & McLachlan, J. A. (1993) · Molecular Endocrinology · doi:10.1210/mend.7.8.8232319 · Cited by 325 · see citing works
Thompson, W. J., Terasaki, W. L., Epstein, P. M., & Sj, S. (1979) · PubMed · Cited by 242 · see citing works
Biochemical Actions of Hormones
(1980) · Elsevier eBooks · doi:10.1016/b978-0-12-452807-9.x5001-3 · Cited by 206 · see citing works
Beck, C. A., Weigel, N. L., Moyer, M. L., Nordeen, S. K., & Edwards, D. P. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.10.4441 · Cited by 205 · see citing works
Cho, H., & Katzenellenbogen, B. S. (1993) · Molecular Endocrinology · doi:10.1210/mend.7.3.7683375 · Cited by 202 · see citing works
Self-citationEstrogen receptors in uterine plasma membrane
Pietras, R. J., & Szego, C. M. (1979) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(79)90124-9 · Cited by 177 · see citing works
Sartorius, C. A., Tung, L. W., Takimoto, G. S., & Horwitz, K. B. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)98344-4 · Cited by 176 · see citing works
Lieberherr, M., Grosse, B., Kachkache, M., & BALSAN, S. (1993) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650081111 · Cited by 174 · see citing works
Kraus, W. L., Montano, M. M., & Katzenellenbogen, B. S. (1993) · Molecular Endocrinology · doi:10.1210/mend.7.12.8145766 · Cited by 174 · see citing works
Self-citationModulation of glucocorticoid receptor function by protein kinase A.
Rangarajan, P. N., Umesono, K., & Evans, R. M. (1992) · Molecular Endocrinology · doi:10.1210/mend.6.9.1435789 · Cited by 159 · see citing works
Rosenfeld, M. G., & O’Malley, B. W. (1970) · Science · doi:10.1126/science.168.3928.253 · Cited by 128 · see citing works
Reese, J. C., & Katzenellenbogen, B. S. (1991) · Nucleic Acids Research · doi:10.1093/nar/19.23.6595 · Cited by 127 · see citing works
Self-citationFujimoto, N., & Katzenellenbogen, B. S. (1994) · Molecular Endocrinology · doi:10.1210/mend.8.3.7517003 · Cited by 124 · see citing works
Self-citationImmediate and transient stimulation of protein tyrosine phosphorylation by estradiol in MCF-7 cells.
Migliaccio, A., Pagano, M. A., & Auricchio, F. (1993) · PubMed · Cited by 118 · see citing works
Gametchu, B., Watson, C. S., & Wu, S. (1993) · The FASEB Journal · doi:10.1096/fasebj.7.13.8405814 · Cited by 117 · see citing works
Tischkau, S. A., & RAMIREZ, V. D. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.4.1285 · Cited by 106 · see citing works
Estrogen-Related Increases in Uterine Guanosine 3′:5′-Cyclic Monophosphate Levels
Kuehl, F. A., Ham, E. A., Zanetti, M. E., et al. (1974) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.71.5.1866 · Cited by 102 · see citing works
In vivo, cAMP stimulates growth and morphogenesis of mouse mammary ducts.
Silberstein, G. B., Strickland, P. A., Trumpbour, V., et al. (1984) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.81.15.4950 · Cited by 69 · see citing works
Somers, J. P., & DeFranco, D. B. (1992) · Molecular Endocrinology · doi:10.1210/mend.6.1.1310797 · Cited by 64 · see citing works
Bársony, J., & Marx, S. J. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.4.1223 · Cited by 61 · see citing works
Perturbations in the Model of Estrogen Receptor Regulation of Gene Expression1
Gorski, J., Furlow, J. D., Murdoch, F. E., Fritsch, M. K., Kaneko, K. J., Ying, C., & Malayer, J. R. (1993) · Biology of Reproduction · doi:10.1095/biolreprod48.1.8 · Cited by 58 · see citing works
Gruol, D. J., & Altschmied, J. (1993) · Molecular Endocrinology · doi:10.1210/mend.7.1.8383286 · Cited by 55 · see citing works
Sanborn, B. M., Bhalla, R. C., & Korenman, S. G. (1973) · Endocrinology · doi:10.1210/endo-92-2-494 · Cited by 52 · see citing works
Szego, C. M., & Davis, J. S. (1969) · PubMed · Cited by 43 · see citing works
Subcellular compartmentalization of MCF-7 estrogen receptor synthesis and degradation
Welshons, W. V., Grady, L. H., Judy, B. M., Jordan, V. C., & Preziosi, D. E. (1993) · Molecular and Cellular Endocrinology · doi:10.1016/0303-7207(93)90167-i · Cited by 35 · see citing works
Sheffield, L. G., & Welsch, C. W. (1985) · International Journal of Cancer · doi:10.1002/ijc.2910360411 · Cited by 30 · see citing works
Intrauterine Injection of Cholera Toxin Induces Estrogen-Like Uterine Growth 1
Stewart, P. J., & Webster, R. A. (1983) · Biology of Reproduction · doi:10.1095/biolreprod29.3.671 · Cited by 27 · see citing works
Estrogenic regulation of uterine cyclic amp metabolism
Chew, C. S., & Rinard, G. A. (1974) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/0304-4165(74)90144-5 · Cited by 24 · see citing works
Dupont-Mairesse, N., Sande, J. V., Rooryck, J., et al. (1974) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(74)90125-3 · Cited by 15 · see citing works
Fanidi, A., Ahnadi, C.-E., Fayard, J., et al. (1992) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/0960-0760(92)90386-w · Cited by 9 · see citing works
Flagged first, then by citations
Research works printed but not linked: 9
- Silberstein, G. B., Strickland, P. & Trumpbour, V. (1984) Proc. Nat!. Acad. Sci. USA 81, 4950-4954.
- Szego, C. M. & Davis, J. S. (1967) Proc. Nat!. Acad. Sci. USA 58, 1711-1718.
- Kuehl, F. A., Jr., Ham, E. A., Zanetti, M. E., Sanford, C. H., Nicol, S. E. & Goldberg, N. D. (1974) Proc. Nat!. Acad. Sci. USA 71, 1866- 1870.
- Beck, C. A., Weigel, N. L., Moyer, M. L., Nordeen, S. K. & Edwards, D. P. (1993) Proc. Natl. Acad. Sci. USA 90, 4441-4445.
- Montminy, M. R., Sevarino, K. A., Wagner, J. A., Mandel, G. & Goodman, R. H. (1986) Proc. Natl. Acad. Sci. USA 83, 6682-6686.
- Berry, M., Nunez, A. & Chambon, P. (1989) Proc. Nat!. Acad. Sci. USA 86, 1218-1222.
- Prosser, R. A. (1989) Ph.D. thesis (Univ. Illinois, Urbana).
- Tischkau, S. A. & Ramirez, V. D. (1993) Proc. Natl. Acad. Sci. USA 90, 1285-1289.
- Barsony, J. & Marx, S. J. (1988) Proc. Nat!. Acad. Sci. USA 85, 1223-1226.
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Couse, J. F., & Korach, K. S. (1999) · Endocrine Reviews · doi:10.1210/edrv.20.3.0370 · Cited by 2,045 · see citing works
Overview of nomenclature of nuclear receptors
Germain, P., Staels, B., Dacquet, C., Spedding, M., & Laudet, V. (2006) · Pharmacological Reviews · doi:10.1124/pr.58.4.2 · Cited by 688 · see citing works
The molecular bases of Alzheimer’s disease and other neurodegenerative disorders
Maccioni, R. B., Muñoz, J. P., & Barbeito, L. (2001) · Archives of Medical Research · doi:10.1016/s0188-4409(01)00316-2 · Cited by 474 · see citing works
Zouboulis, C., Chen, W.-C., Thornton, M., Qin, K., & Rosenfield, R. (2007) · Hormone and Metabolic Research · doi:10.1055/s-2007-961807 · Cited by 379 · see citing works
The unfolding stories of GPR30, a new membrane-bound estrogen receptor
Maggiolini, M., & Picard, D. (2010) · Journal of Endocrinology · doi:10.1677/joe-09-0242 · Cited by 360 · see citing works
Estrogen-induced cardiorenal protection: potential cellular, biochemical and molecular mechanisms.
Dubey, R. K., & Jackson, E. K. (2001) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.2001.280.3.f365 · Cited by 263 · see citing works
Estrogen receptor α is essential for induction of oxytocin receptor by estrogen
Young, L. J., Wang, Z., Donaldson, R., & Rissman, E. F. (1998) · Neuroreport · doi:10.1097/00001756-199803300-00031 · Cited by 198 · see citing works
Cellular Functions of the Plasma Membrane Estrogen Receptor
Levin, E. R. (1999) · Trends in Endocrinology & Metabolism · doi:10.1016/s1043-2760(99)00192-7 · Cited by 179 · see citing works
Membrane estradiol signaling in the brain
Micevych, P., & Dominguez, R. (2009) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2009.04.011 · Cited by 177 · see citing works
Tang, W.-Y., Morey, L. M., Cheung, Y. Y., Birch, L., Prins, G. S., & Ho, S.-M. (2012) · Endocrinology · doi:10.1210/en.2011-1308 · Cited by 164 · see citing works
Sex differences in stress responses: focus on ovarian hormones
Ter Horst, G. J., Wichmann, R., Gerrits, M., Westenbroek, C., & Lin, Y. (2009) · Physiology & Behavior · doi:10.1016/j.physbeh.2009.02.036 · Cited by 157 · see citing works
Oestrogen functions in skin and skin appendages
Thornton, M. J. (2005) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.9.3.617 · Cited by 82 · see citing works
Zhao, X.-F. (2020) · Cell Communication and Signaling · doi:10.1186/s12964-020-00620-y · Cited by 60 · see citing works
Speert, D. B., McClennen, S. J., & Seasholtz, A. F. (2002) · Endocrinology · doi:10.1210/en.2002-220556 · Cited by 55 · see citing works
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Cai, M.-J., Dong, D.-J., Wang, Y., Liu, P.-C., Liu, W., Wang, J.-X., & Zhao, X.-F. (2014) · Cell Communication and Signaling · doi:10.1186/1478-811x-12-9 · Cited by 44 · see citing works
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Silva, R. D. C. P. D. C. E., Moura, K. K. V. D. O., Ribeiro Júnior, C. L., & Guillo, L. A. (2016) · Revista da Associação Médica Brasileira · doi:10.1590/1806-9282.62.01.72 · Cited by 21 · see citing works
- Authors
- Aronica, S. M., Kraus, W. L., & Katzenellenbogen, B. S.
- Affiliations
- University of Illinois Urbana-Champaign (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1994-08-30
- Volume
- 91
- Issue
- 18
- Pages
- 8517-8521
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC44637
- OpenAlex
- W2051596977
- Cited by
- 670
- References
- 40
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 7 · 2023: 7 · 2022: 12 · 2021: 12 · 2020: 16 · 2019: 9 · 2018: 11 · 2017: 8 · 2016: 16 · 2015: 14 · 2014: 17 · 2013: 25 · 2012: 21
- FWCI
- 10.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ca051482-08)
- National Cancer Institute (CA 51482, CA 18119)
- National Institute of General Medical Sciences (T32GM007143, 5 T32 GM7143)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Keywords
- estrogen, cAMP signaling, adenylate cyclase, non-genomic estrogen signaling, estradiol, antiestrogens, cAMP response element, gene transcription, second messengers, breast cancer cells, uterine cells
- MeSH terms
- Cyclic AMP, Adenylyl Cyclases, Animals, Base Sequence, Breast Neoplasms, Cells, Cultured, Estradiol, Female, Gene Expression Regulation, Humans, Molecular Sequence Data, Oligodeoxyribonucleotides, Tamoxifen, Transcription, Genetic, Tumor Cells, Cultured, Uterus, Signal Transduction, Rats, Sprague-Dawley, Rats, Polyunsaturated Alkamides, In Vitro Techniques
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