help button home button Endocrine Society Endocrine Reviews
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Reprints, Permissions and Rights
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by McLachlan, J. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by McLachlan, J. A.
Endocrine Reviews 22 (3): 319-341
Copyright © 2001 by The Endocrine Society

Environmental Signaling: What Embryos and Evolution Teach Us About Endocrine Disrupting Chemicals

John A. McLachlan

Department of Pharmacology, Tulane University Health Sciences Center, Environmental Endocrinology Laboratory, Center for Bioenvironmental Research, Tulane and Xavier Universities, New Orleans, Louisiana 70112–2699

The term "endocrine disrupting chemicals" is commonly used to describe environmental agents that alter the endocrine system. Laboratories working in this emerging field—environmental endocrine research—have looked at chemicals that mimic or block endogenous vertebrate steroid hormones by interacting with the hormone’s receptor.

Environmental chemicals known to do this do so most often with receptors derived from the steroid/thyroid/retinoid gene family. They include ubiquitous and persistent organochlorines, as well as plasticizers, pharmaceuticals, and natural hormones. These chemicals function as estrogens, antiestrogens, and antiandrogens but have few, if any, structural similarities. Therefore, receptor-based or functional assays have the best chance of detecting putative biological activity of environmental chemicals. Three nuclear estrogen receptor forms—{alpha}, ß, and {gamma}—as well as multiple membrane forms and a possible mitochondrial form have been reported, suggesting a previously unknown diversity of signaling pathways available to estrogenic chemicals.

Examples of environmental or ambient estrogenization occur in laboratory experiments, zoo animals, domestic animals, wildlife, and humans. Environmentally estrogenized phenotypes may differ depending upon the time of exposure—i.e., whether the exposure occurred at a developmental (organizational and irreversible) or postdevelopmental (activational and reversible) stage. The term "estrogen" must be defined in each case, since steroidal estrogens differ among themselves and from synthetic or plant-derived chemicals.

An "estrogen-like function" seems to be an evolutionarily ancient signal that has been retained in a number of chemicals, some of which are vertebrate hormones. Signaling, required for symbiosis between plants and bacteria, may be viewed, therefore, as an early example of hormone cross-talk.

Developmental feminization at the structural or functional level is an emerging theme in species exposed, during embryonic or fetal life, to estrogenic compounds. Human experience as well as studies in experimental animals with the potent estrogen diethylstilbestrol provide informative models. Advances in the molecular genetics of sex differentiation in vertebrates facilitate mechanistic understanding. Experiments addressing the concept of gene imprinting or induction of epigenetic memory by estrogen or other hormones suggest a link to persistent, heritable phenotypic changes seen after developmental estrogenization, independent of mutagenesis.

Environmental endocrine science provides a new context in which to examine the informational content of ecosystem-wide communication networks. As common features come to light, this research may allow us to predict environmentally induced alterations in internal signaling systems of vertebrates and some invertebrates and eventually to explicate environmental contributions to human reproductive and developmental health.




This article has been cited by other articles:


Home page
Biol. Reprod.Home page
E. D. Albrecht, M. V. Lane, G. R. Marshall, I. Merchenthaler, D. R. Simorangkir, C. R. Pohl, T. M. Plant, and G. J. Pepe
Estrogen Promotes Germ Cell and Seminiferous Tubule Development in the Baboon Fetal Testis
Biol Reprod, August 1, 2009; 81(2): 406 - 414.
[Abstract] [Full Text] [PDF]


Home page
EndocrinologyHome page
J. Keay and J. W. Thornton
Hormone-Activated Estrogen Receptors in Annelid Invertebrates: Implications for Evolution and Endocrine Disruption
Endocrinology, April 1, 2009; 150(4): 1731 - 1738.
[Abstract] [Full Text] [PDF]


Home page
EndocrinologyHome page
Y. Katsu, S. Kohno, S. Hyodo, S. Ijiri, S. Adachi, A. Hara, L. J. Guillette Jr., and T. Iguchi
Molecular Cloning, Characterization, and Evolutionary Analysis of Estrogen Receptors from Phylogenetically Ancient Fish
Endocrinology, December 1, 2008; 149(12): 6300 - 6310.
[Abstract] [Full Text] [PDF]


Home page
EndocrinologyHome page
S. E. Recabarren, P. P. Rojas-Garcia, M. P. Recabarren, V. H. Alfaro, R. Smith, V. Padmanabhan, and T. Sir-Petermann
Prenatal Testosterone Excess Reduces Sperm Count and Motility
Endocrinology, December 1, 2008; 149(12): 6444 - 6448.
[Abstract] [Full Text] [PDF]


Home page
Endocr. Rev.Home page
C. Foresta, D. Zuccarello, A. Garolla, and A. Ferlin
Role of Hormones, Genes, and Environment in Human Cryptorchidism
Endocr. Rev., August 1, 2008; 29(5): 560 - 580.
[Abstract] [Full Text] [PDF]


Home page
Toxicol SciHome page
A. L. Zimmermann, E. A. King, E. Dengler, S. R. Scogin, and W. H. Powell
An Aryl Hydrocarbon Receptor Repressor from Xenopus laevis: Function, Expression, and Role in Dioxin Responsiveness during Frog Development
Toxicol. Sci., July 1, 2008; 104(1): 124 - 134.
[Abstract] [Full Text] [PDF]


Home page
EndocrinologyHome page
Y. Katsu, R. Ichikawa, T. Ikeuchi, S. Kohno, L. J. Guillette Jr., and T. Iguchi
Molecular Cloning and Characterization of Estrogen, Androgen, and Progesterone Nuclear Receptors from a Freshwater Turtle (Pseudemys nelsoni)
Endocrinology, January 1, 2008; 149(1): 161 - 173.
[Abstract] [Full Text] [PDF]


Home page
Hum ReprodHome page
M. Watanabe, R. Yoshida, K. Ueoka, K. Aoki, I. Sasagawa, T. Hasegawa, K. Sueoka, N. Kamatani, Y. Yoshimura, and T. Ogata
Haplotype analysis of the estrogen receptor 1 gene in male genital and reproductive abnormalities
Hum. Reprod., May 1, 2007; 22(5): 1279 - 1284.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
D. Crews, A. C. Gore, T. S. Hsu, N. L. Dangleben, M. Spinetta, T. Schallert, M. D. Anway, and M. K. Skinner
Transgenerational epigenetic imprints on mate preference
PNAS, April 3, 2007; 104(14): 5942 - 5946.
[Abstract] [Full Text] [PDF]


Home page
Pharmacol. Rev.Home page
P. Germain, B. Staels, C. Dacquet, M. Spedding, and V. Laudet
Overview of Nomenclature of Nuclear Receptors
Pharmacol. Rev., December 1, 2006; 58(4): 685 - 704.
[Abstract] [Full Text] [PDF]


Home page
Hum ReprodHome page
S. J. Genuis
Health issues and the environment--an emerging paradigm for providers of obstetrical and gynaecological health care
Hum. Reprod., September 1, 2006; 21(9): 2201 - 2208.
[Abstract] [Full Text] [PDF]


Home page
EndocrinologyHome page
D. Crews and J. A. McLachlan
Epigenetics, Evolution, Endocrine Disruption, Health, and Disease
Endocrinology, June 1, 2006; 147(6): s4 - s10.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
S.-M. Ho, W.-Y. Tang, J. Belmonte de Frausto, and G. S. Prins
Developmental Exposure to Estradiol and Bisphenol A Increases Susceptibility to Prostate Carcinogenesis and Epigenetically Regulates Phosphodiesterase Type 4 Variant 4
Cancer Res., June 1, 2006; 66(11): 5624 - 5632.
[Abstract] [Full Text] [PDF]


Home page
Toxicol SciHome page
K. Mizota and H. Ueda
Endocrine Disrupting Chemical Atrazine Causes Degranulation through Gq/11 Protein-Coupled Neurosteroid Receptor in Mast Cells
Toxicol. Sci., April 1, 2006; 90(2): 362 - 368.
[Abstract] [Full Text] [PDF]


Home page
Toxicol SciHome page
R. Opitz, S. Hartmann, T. Blank, T. Braunbeck, I. Lutz, and W. Kloas
Evaluation of Histological and Molecular Endpoints for Enhanced Detection of Thyroid System Disruption in Xenopus laevis Tadpoles
Toxicol. Sci., April 1, 2006; 90(2): 337 - 348.
[Abstract] [Full Text] [PDF]


Home page
J. Exp. Biol.Home page
A. Heyland and L. L. Moroz
Cross-kingdom hormonal signaling: an insight from thyroid hormone functions in marine larvae
J. Exp. Biol., December 1, 2005; 208(23): 4355 - 4361.
[Abstract] [Full Text] [PDF]


Home page
J. Clin. Endocrinol. Metab.Home page
S. Ramaswamy
Pubertal Augmentation in Juvenile Rhesus Monkey Testosterone Production Induced by Invariant Gonadotropin Stimulation Is Inhibited by Estrogen
J. Clin. Endocrinol. Metab., October 1, 2005; 90(10): 5866 - 5875.
[Abstract] [Full Text] [PDF]


Home page
J. Epidemiol. Community HealthHome page
N. Krieger, I. Lowy, R. Aronowitz, J. Bigby, K. Dickersin, E. Garner, J.-P. Gaudilliere, C. Hinestrosa, R. Hubbard, P. A Johnson, et al.
Hormone replacement therapy, cancer, controversies, and women's health: historical, epidemiological, biological, clinical, and advocacy perspectives
J Epidemiol Community Health, September 1, 2005; 59(9): 740 - 748.
[Abstract] [Full Text] [PDF]


Home page
Biol. Reprod.Home page
M.-K. I. Anas, C. Guillemette, P. Ayotte, D. Pereg, F. Giguere, and J. L. Bailey
In Utero and Lactational Exposure to an Environmentally Relevant Organochlorine Mixture Disrupts Reproductive Development and Function in Male Rats
Biol Reprod, September 1, 2005; 73(3): 414 - 426.
[Abstract] [Full Text] [PDF]


Home page
J. Clin. Endocrinol. Metab.Home page
R. Yoshida, M. Fukami, I. Sasagawa, T. Hasegawa, N. Kamatani, and T. Ogata
Association of Cryptorchidism with a Specific Haplotype of the Estrogen Receptor {alpha} Gene: Implication for the Susceptibility to Estrogenic Environmental Endocrine Disruptors
J. Clin. Endocrinol. Metab., August 1, 2005; 90(8): 4716 - 4721.
[Abstract] [Full Text] [PDF]


Home page
EndocrinologyHome page
E. D. Albrecht, G. W. Aberdeen, and G. J. Pepe
Estrogen Elicits Cortical Zone-Specific Effects on Development of the Primate Fetal Adrenal Gland
Endocrinology, April 1, 2005; 146(4): 1737 - 1744.
[Abstract] [Full Text] [PDF]


Home page
EndocrinologyHome page
A. Florin, M. Maire, A. Bozec, A. Hellani, S. Chater, R. Bars, F. Chuzel, and M. Benahmed
Androgens and Postmeiotic Germ Cells Regulate Claudin-11 Expression in Rat Sertoli Cells
Endocrinology, March 1, 2005; 146(3): 1532 - 1540.
[Abstract] [Full Text] [PDF]


Home page
J. Clin. Endocrinol. Metab.Home page
R. Jasuja, P. Ramaraj, R. P. Mac, A. B. Singh, T. W. Storer, J. Artaza, A. Miller, R. Singh, W. E. Taylor, M. L. Lee, et al.
{Delta}-4-Androstene-3,17-Dione Binds Androgen Receptor, Promotes Myogenesis in Vitro, and Increases Serum Testosterone Levels, Fat-Free Mass, and Muscle Strength in Hypogonadal Men
J. Clin. Endocrinol. Metab., February 1, 2005; 90(2): 855 - 863.
[Abstract] [Full Text] [PDF]


Home page
Integr. Comp. Biol.Home page
R. D. Stevenson, S. R. Tuberty, P. L. deFur, and J. C. Wingfield
EcoPhysiology and Conservation: The Contribution of Endocrinology and Immunology- Introduction to the Symposium
Integr. Comp. Biol., January 1, 2005; 45(1): 1 - 3.
[Full Text] [PDF]


Home page
Integr. Comp. Biol.Home page
L. J. Guillette Jr. and T. M. Edwards
Is Nitrate an Ecologically Relevant Endocrine Disruptor in Vertebrates?
Integr. Comp. Biol., January 1, 2005; 45(1): 19 - 27.
[Abstract] [Full Text] [PDF]


Home page
Integr. Comp. Biol.Home page
E. Zou
Impacts of Xenobiotics on Crustacean Molting: The Invisible Endocrine Disruption
Integr. Comp. Biol., January 1, 2005; 45(1): 33 - 38.
[Abstract] [Full Text] [PDF]


Home page
Integr. Comp. Biol.Home page
A. M. Tarrant
Endocrine-like Signaling in Cnidarians: Current Understanding and Implications for Ecophysiology
Integr. Comp. Biol., January 1, 2005; 45(1): 201 - 214.
[Abstract] [Full Text] [PDF]


Home page
Toxicol SciHome page
K. Ohno, N. Araki, T. Yanase, H. Nawata, and M. Iida
A Novel Nonradioactive Method for Measuring Aromatase Activity Using a Human Ovarian Granulosa-Like Tumor Cell Line and an Estrone ELISA
Toxicol. Sci., December 1, 2004; 82(2): 443 - 450.
[Abstract] [Full Text] [PDF]


Home page
J EndocrinolHome page
A Bozec, F Chuzel, S Chater, C Paulin, R Bars, M Benahmed, and C Mauduit
The mitochondrial-dependent pathway is chronically affected in testicular germ cell death in adult rats exposed in utero to anti-androgens
J. Endocrinol., October 1, 2004; 183(1): 79 - 90.
[Abstract] [Full Text] [PDF]


Home page
Hum ReprodHome page
A. Rignell-Hydbom, L. Rylander, A. Giwercman, B.A.G. Jonsson, P. Nilsson-Ehle, and L. Hagmar
Exposure to CB-153 and p,p'-DDE and male reproductive function
Hum. Reprod., September 1, 2004; 19(9): 2066 - 2075.
[Abstract] [Full Text] [PDF]


Home page
EndocrinologyHome page
H. Morinaga, T. Yanase, M. Nomura, T. Okabe, K. Goto, N. Harada, and H. Nawata
A Benzimidazole Fungicide, Benomyl, and Its Metabolite, Carbendazim, Induce Aromatase Activity in a Human Ovarian Granulose-Like Tumor Cell Line (KGN)
Endocrinology, April 1, 2004; 145(4): 1860 - 1869.
[Abstract] [Full Text] [PDF]


Home page
Endocr. Rev.Home page
A.-S. Parent, G. Teilmann, A. Juul, N. E. Skakkebaek, J. Toppari, and J.-P. Bourguignon
The Timing of Normal Puberty and the Age Limits of Sexual Precocity: Variations around the World, Secular Trends, and Changes after Migration
Endocr. Rev., October 1, 2003; 24(5): 668 - 693.
[Abstract] [Full Text] [PDF]


Home page
CarcinogenesisHome page
B. Mograbi, E. Corcelle, N. Defamie, M. Samson, M. Nebout, D. Segretain, P. Fenichel, and G. Pointis
Aberrant Connexin 43 endocytosis by the carcinogen lindane involves activation of the ERK/mitogen-activated protein kinase pathway
Carcinogenesis, August 1, 2003; 24(8): 1415 - 1423.
[Abstract] [Full Text] [PDF]


Home page
EndocrinologyHome page
J. G. Ramos, J. Varayoud, L. Kass, H. Rodriguez, L. Costabel, M. Munoz-de-Toro, and E. H. Luque
Bisphenol A Induces Both Transient and Permanent Histofunctional Alterations of the Hypothalamic-Pituitary-Gonadal Axis in Prenatally Exposed Male Rats
Endocrinology, July 1, 2003; 144(7): 3206 - 3215.
[Abstract] [Full Text] [PDF]


Home page
EndocrinologyHome page
M. B. Martin, R. Reiter, T. Pham, Y. R. Avellanet, J. Camara, M. Lahm, E. Pentecost, K. Pratap, B. A. Gilmore, S. Divekar, et al.
Estrogen-Like Activity of Metals in Mcf-7 Breast Cancer Cells
Endocrinology, June 1, 2003; 144(6): 2425 - 2436.
[Abstract] [Full Text] [PDF]


Home page
Toxicol SciHome page
J. Lassurguere, G. Livera, R. Habert, and B. Jegou
Time- and Dose-Related Effects of Estradiol and Diethylstilbestrol on the Morphology and Function of the Fetal Rat Testis in Culture
Toxicol. Sci., May 1, 2003; 73(1): 160 - 169.
[Abstract] [Full Text] [PDF]


Home page
Biol. Reprod.Home page
R. Thuillier, Y. Wang, and M. Culty
Prenatal Exposure to Estrogenic Compounds Alters the Expression Pattern of Platelet-Derived Growth Factor Receptors {alpha} and {beta} in Neonatal Rat Testis: Identification of Gonocytes as Targets of Estrogen Exposure
Biol Reprod, March 1, 2003; 68(3): 867 - 880.
[Abstract] [Full Text] [PDF]


Home page
EndocrinologyHome page
A. Omezzine, S. Chater, C. Mauduit, A. Florin, E. Tabone, F. Chuzel, R. Bars, and M. Benahmed
Long-Term Apoptotic Cell Death Process with Increased Expression and Activation of Caspase-3 and -6 in Adult Rat Germ Cells Exposed in Utero to Flutamide
Endocrinology, February 1, 2003; 144(2): 648 - 661.
[Abstract] [Full Text] [PDF]


Home page
EndocrinologyHome page
K.-H. Song, K. Lee, and H.-S. Choi
Endocrine Disrupter Bisphenol A Induces Orphan Nuclear Receptor Nur77 Gene Expression and Steroidogenesis in Mouse Testicular Leydig Cells
Endocrinology, June 1, 2002; 143(6): 2208 - 2215.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2001 by The Endocrine Society