Editing Endocrine disruptor (section)

== Endocrine system ==
{{Main|Endocrine system}}
[[File:Endocrine English.svg|thumb|[[Endocrine system]] diagram within a human body.]]
Endocrine systems are found in most varieties of [[animal]]s. The endocrine system consists of [[gland]]s that secrete [[hormone]]s, and [[receptor (biochemistry)|receptors]] that detect and react to the hormones.<ref>{{Cite web |date=19 November 2019 |title=Anatomy of the Endocrine System |url=https://www.hopkinsmedicine.org/health/wellness-and-prevention/anatomy-of-the-endocrine-system |access-date=11 April 2023 | work = Johns Hopkins Medicine |language=en}}</ref>

Hormones travel throughout the body via the bloodstream and act as chemical messengers.<ref>{{Cite web |last=Services |first=Department of Health & Human |title=Hormonal (endocrine) system |url=https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/hormonal-endocrine-system#bhc-content |access-date=2025-02-09 |website=www.betterhealth.vic.gov.au |language=en}}</ref> Hormones interface with cells that contain matching receptors in or on their surfaces. The hormone binds with the receptor, much like a key would fit into a lock. The endocrine system regulates adjustments through slower internal processes, using hormones as messengers. The endocrine system secretes hormones in response to environmental stimuli and to orchestrate developmental and reproductive changes. The adjustments brought on by the endocrine system are biochemical, changing the cell's internal and external chemistry to bring about a long term change in the body.<ref>{{Cite web |title=Hormonal (endocrine) system |url=http://www.betterhealth.vic.gov.au/health/conditionsandtreatments/hormonal-endocrine-system |access-date=11 April 2023 | work = Better Health Channel | publisher = The Department of Health, Victorian Government |language=en}}</ref> These systems work together to maintain the proper functioning of the body through its entire life cycle. [[Sex steroids]] such as [[estrogens]] and [[androgens]], as well as [[thyroid]] hormones, are subject to [[feedback]] regulation, which tends to limit the sensitivity of these glands.<ref>{{cite journal | vauthors = Kim YJ, Tamadon A, Park HT, Kim H, Ku SY | title = The role of sex steroid hormones in the pathophysiology and treatment of sarcopenia | journal = Osteoporosis and Sarcopenia | volume = 2 | issue = 3 | pages = 140–155 | date = September 2016 | pmid = 30775480 | pmc = 6372754 | doi = 10.1016/j.afos.2016.06.002 }}</ref>

Hormones work at very small doses (part per billion ranges).<ref>{{Cite journal |last1=Vandenberg |first1=Laura N. |last2=Colborn |first2=Theo |last3=Hayes |first3=Tyrone B. |last4=Heindel |first4=Jerrold J. |last5=Jacobs |first5=David R. |last6=Lee |first6=Duk-Hee |last7=Shioda |first7=Toshi |last8=Soto |first8=Ana M. |last9=vom Saal |first9=Frederick S. |last10=Welshons |first10=Wade V. |last11=Zoeller |first11=R. Thomas |last12=Myers |first12=John Peterson |date=2012-06-01 |title=Hormones and Endocrine-Disrupting Chemicals: Low-Dose Effects and Nonmonotonic Dose Responses |journal=Endocrine Reviews |language=en |volume=33 |issue=3 |pages=378–455 |doi=10.1210/er.2011-1050 |issn=0163-769X |pmc=3365860 |pmid=22419778}}</ref>  Endocrine disruption can thereby also occur from low-dose exposure to exogenous hormones or hormonally active chemicals such as [[BPA controversy|bisphenol A]].  These chemicals can bind to receptors for other hormonally mediated processes.<ref>{{cite web |title=Bisphenol A Overview |publisher=Environment California |url=http://www.environmentcalifornia.org/environmental-health/stop-toxic-toys/bisphenol-a-overview |archive-url=https://web.archive.org/web/20110422170104/http://www.environmentcalifornia.org/environmental-health/stop-toxic-toys/bisphenol-a-overview |archive-date=22 April 2011}}</ref> Furthermore, since [[endogenous]] hormones are already present in the body in biologically active concentrations, additional exposure to relatively small amounts of [[exogenous]] hormonally active substances can disrupt the proper functioning of the body's endocrine system. Thus, an endocrine disruptor can elicit adverse effects at much lower doses than a toxicity, acting through a different mechanism.

The timing of exposure is also critical.  Most critical stages of development occur in utero, where the fertilized egg divides, rapidly developing every structure of a fully formed baby, including much of the wiring in the brain.  Interfering with the hormonal communication in utero can have profound effects both structurally and toward brain development. Depending on the stage of reproductive development, interference with hormonal signaling can result in irreversible effects not seen in adults exposed to the same dose for the same length of time.<ref name="Guo_1995">{{cite journal |vauthors=Guo YL, Lambert GH, Hsu CC | title = Growth abnormalities in the population exposed in utero and early postnatally to polychlorinated biphenyls and dibenzofurans | journal = Environ. Health Perspect. | issue = Suppl 6 | pages = 117–22 |date=September 1995 | volume = 103  | pmid = 8549457 | pmc = 1518940 | doi = 10.2307/3432359 | jstor = 3432359 }}</ref><ref name="Bigsby_1999">{{cite journal |vauthors=Bigsby R, Chapin RE, Daston GP, Davis BJ, Gorski J, Gray LE, Howdeshell KL, Zoeller RT, vom Saal FS | title = Evaluating the effects of endocrine disruptors on endocrine function during development | journal = Environ. Health Perspect. | pages = 613–8 |date=August 1999 | volume = 107  | issue = Suppl 4 | pmid = 10421771 | pmc = 1567510 | doi = 10.2307/3434553 | jstor = 3434553 }}</ref><ref name="pmid18848954">{{cite journal |vauthors=Castro DJ, Löhr CV, Fischer KA, Pereira CB, Williams DE | title = Lymphoma and lung cancer in offspring born to pregnant mice dosed with dibenzo[a, l]pyrene: the importance of in utero vs. lactational exposure | journal = Toxicol. Appl. Pharmacol. | volume = 233 | issue = 3 | pages = 454–8 |date=December 2008 | pmid = 18848954 | doi = 10.1016/j.taap.2008.09.009 | pmc = 2729560 | bibcode = 2008ToxAP.233..454C }}</ref>  Experiments with animals have identified critical developmental time points in utero and days after birth when exposure to chemicals that interfere with or mimic hormones have adverse effects that persist into adulthood.<ref name="Bigsby_1999"/><ref name="Eriksson_1991">{{cite journal |vauthors=Eriksson P, Lundkvist U, Fredriksson A | title = Neonatal exposure to 3,3′,4,4′-tetrachlorobiphenyl: changes in spontaneous behaviour and cholinergic muscarinic receptors in the adult mouse | journal = Toxicology | volume = 69 | issue = 1 | pages = 27–34 | year = 1991 | pmid = 1926153 | doi = 10.1016/0300-483X(91)90150-Y }}</ref><ref name="Recabarren_2008">{{cite journal |vauthors=Recabarren SE, Rojas-García PP, Recabarren MP, Alfaro VH, Smith R, Padmanabhan V, -Petermann T | title = Prenatal testosterone excess reduces sperm count and motility | journal = Endocrinology | volume = 149 | issue = 12 | pages = 6444–8 |date=December 2008 | pmid = 18669598 | doi = 10.1210/en.2008-0785 | doi-access = free }}</ref><ref name="Szabo_2009">{{cite journal |vauthors=Szabo DT, Richardson VM, Ross DG, Diliberto JJ, Kodavanti PR, Birnbaum LS | title = Effects of perinatal PBDE exposure on hepatic phase I, phase II, phase III, and deiodinase 1 gene expression involved in thyroid hormone metabolism in male rat pups | journal = Toxicol. Sci. | volume = 107 | issue = 1 | pages = 27–39 |date=January 2009 | pmid = 18978342 | doi = 10.1093/toxsci/kfn230 | pmc = 2638650 }}</ref> Disruption of thyroid function early in development may be the cause of abnormal sexual development in both males<ref name="Lilienthal_2006">{{cite journal |vauthors=Lilienthal H, Hack A, Roth-Härer A, Grande SW, Talsness CE | title = Effects of developmental exposure to 2,2′,4,4′,5-pentabromodiphenyl ether (PBDE-99) on sex steroids, sexual development, and sexually dimorphic behavior in rats | journal =  Environmental Health Perspectives| volume = 114 | issue = 2 | pages = 194–201 |date=February 2006 | pmid = 16451854 | pmc = 1367831 | doi = 10.1289/ehp.8391 | bibcode = 2006EnvHP.114..194L }}</ref> and females<ref name="Talsness_2005">{{cite journal |vauthors=Talsness CE, Shakibaei M, Kuriyama SN, Grande SW, Sterner-Kock A, Schnitker P, de Souza C, Grote K, Chahoud I | title = Ultrastructural changes observed in rat ovaries following in utero and lactational exposure to low doses of a polybrominated flame retardant | journal = Toxicol. Lett. | volume = 157 | issue = 3 | pages = 189–202 |date=July 2005 | pmid = 15917144 | doi = 10.1016/j.toxlet.2005.02.001 }}</ref> early motor development impairment,<ref name="Eriksson_2002">{{cite journal |vauthors=Eriksson P, Viberg H, Jakobsson E, Orn U, Fredriksson A | title = A brominated flame retardant, 2,2′,4,4′,5-pentabromodiphenyl ether: uptake, retention, and induction of neurobehavioral alterations in mice during a critical phase of neonatal brain development | journal = Toxicol. Sci. | volume = 67 | issue = 1 | pages = 98–103 |date=May 2002 | pmid = 11961221 | doi = 10.1093/toxsci/67.1.98 | doi-access = free }}</ref> and learning disabilities.<ref name="pmid16611620">{{cite journal |vauthors=Viberg H, Johansson N, Fredriksson A, Eriksson J, Marsh G, Eriksson P | title = Neonatal exposure to higher brominated diphenyl ethers, hepta-, octa-, or nonabromodiphenyl ether, impairs spontaneous behavior and learning and memory functions of adult mice | journal = Toxicol. Sci. | volume = 92 | issue = 1 | pages = 211–8 |date=July 2006 | pmid = 16611620 | doi = 10.1093/toxsci/kfj196 | doi-access = free }}</ref>

There are studies of cell cultures, laboratory animals, wildlife, and accidentally exposed humans that show that environmental chemicals cause a wide range of reproductive, developmental, growth, and behavior effects, and so while "endocrine disruption in humans by pollutant chemicals remains largely undemonstrated, the underlying science is sound and the potential for such effects is real."<ref name="pmid12837917">{{cite journal |vauthors=Rogan WJ, Ragan NB | title = Evidence of effects of environmental chemicals on the endocrine system in children | journal = Pediatrics | volume = 112 | issue = 1 Pt 2 | pages = 247–52 |date=July 2003 | pmid = 12837917 | url=http://pediatrics.aappublications.org/content/112/Supplement_1/247.full | doi=10.1542/peds.112.S1.247 | s2cid = 13058233 }}</ref> While compounds that produce estrogenic, androgenic, [[antiandrogen]]ic, and [[Antithyroid agent|antithyroid]] actions have been studied, less is known about interactions with other hormones.

The interrelationships between exposures to chemicals and health effects are rather complex. It is hard to definitively link a particular chemical with a specific health effect, and exposed adults may not show any ill effects. But, fetuses and embryos, whose growth and development are highly controlled by the endocrine system, are more vulnerable to exposure and may develop overt or subtle lifelong health or reproductive abnormalities.<ref name="pmid1425407">{{cite journal | vauthors = Bern HA | title = The development of the role of hormones in development—a double remembrance | journal = Endocrinology | volume = 131 | issue = 5 | pages = 2037–8 |date=November 1992 | pmid = 1425407 | doi = 10.1210/endo.131.5.1425407 }}</ref> Prebirth exposure, in some cases, can lead to permanent alterations and adult diseases.<ref name = "Colborn_2007">{{cite journal |vauthors=Colborn T, Carroll LE | s2cid = 34600913 | year = 2007 | title = Pesticides, sexual development, reproduction, and fertility: current perspective and future | journal = Human and Ecological Risk Assessment | volume = 13 | issue = 5 | pages = 1078–1110 | doi = 10.1080/10807030701506405}}</ref>

Some in the scientific community are concerned that exposure to endocrine disruptors in the womb or early in life may be associated with [[neurodevelopmental disorder]]s including reduced IQ, [[ADHD]], and [[autism]].<ref name="urlwww.iceh.org">{{cite web |author1=Collaborative on Health |author2=the Environment's Learning |author3=Developmental Disabilities Initiative |date=1 July 2008 |title=Scientific Consensus Statement on Environmental Agents Associated with Neurodevelopmental Disorders |url=https://www.healthandenvironment.org/uploads-old/LDDIStatement.pdf |access-date=14 March 2009 |publisher=Institute for Children's Environmental Health}}</ref> Certain cancers and uterine abnormalities in women are associated with exposure to [[diethylstilbestrol]] (DES) in the womb due to DES used as a medical treatment.

In a 2005 publication, [[phthalate]]s in pregnant women's urine was linked to subtle, but specific, genital changes in their male infants—a shorter, more female-like [[anogenital distance]] and associated incomplete descent of testes and a smaller scrotum and penis.<ref name="Swan_2005">{{cite journal |vauthors=Swan SH, Main KM, Liu F, Stewart SL, Kruse RL, Calafat AM, Mao CS, Redmon JB, Ternand CL, Sullivan S, Teague JL | title = Decrease in anogenital distance among male infants with prenatal phthalate exposure | journal = Environmental Health Perspectives| volume = 113 | issue = 8 | pages = 1056–61 |date=August 2005 | pmid = 16079079 | pmc = 1280349 | doi = 10.1289/ehp.8100 | bibcode = 2005EnvHP.113.1056S }}</ref> The science behind this study was questioned by phthalate industry consultants,<ref name="pmid16393642">{{cite journal | vauthors = McEwen GN, Renner G | title = Validity of anogenital distance as a marker of in utero phthalate exposure | journal = Environmental Health Perspectives| volume = 114 | issue = 1 | pages = A19–20; author reply A20–1 | date = January 2006 | pmid = 16393642 | pmc = 1332693 | doi = 10.1289/ehp.114-1332693 }}</ref> and back in 2008, there were only five studies of anogenital distance in humans,<ref name="pmid18519505">{{cite journal | vauthors = Postellon DC | title = Baby care products | journal = Pediatrics | volume = 121 | issue = 6 | pages = 1292; author reply 1292–3 |date=June 2008 | pmid = 18519505 | doi = 10.1542/peds.2008-0401 | s2cid = 27956545 }}</ref> with one researcher stating, "Whether AGD measures in humans relate to clinically important outcomes, however, remains to be determined, as does its utility as a measure of androgen action in epidemiological studies."<ref name="pmid17439530">{{cite journal |vauthors=Romano-Riquer SP, Hernández-Avila M, [[Beth Gladen|Gladen BC]], Cupul-Uicab LA, Longnecker MP | title = Reliability and determinants of anogenital distance and penis dimensions in male newborns from Chiapas, Mexico | journal = Paediatr Perinat Epidemiol | volume = 21 | issue = 3 | pages = 219–28 |date=May 2007 | pmid = 17439530 | doi = 10.1111/j.1365-3016.2007.00810.x | pmc = 3653615 }}</ref> Today, it is well-established that AGD is an indicator of fetal androgen exposure, and several studies have found a correlation between AGD and the incidence of prostate cancer.<ref>{{cite journal | vauthors = Maldonado-Cárceles AB, Sánchez-Rodríguez C, Vera-Porras EM, Árense-Gonzalo JJ, Oñate-Celdrán J, Samper-Mateo P, García-Escudero D, Torres-Roca M, Martínez-Díaz F, Mendiola J, Torres-Cantero AM | title = Anogenital Distance, a Biomarker of Prenatal Androgen Exposure Is Associated With Prostate Cancer Severity | journal = The Prostate | volume = 77 | issue = 4 | pages = 406–411 | date = March 2017 | pmid = 27862129 | doi = 10.1002/pros.23279 }}</ref><ref>{{cite journal | vauthors = Marín-Martínez FM, Arense-Gonzalo JJ, Artes MA, Bobadilla Romero ER, García Porcel VJ, Alcon Cerro P, Suárez-Pineda MC, Guzmán Martínez-Valls PL, Mendiola J | title = Anogenital distance, a biomarker of fetal androgen exposure and the risk of prostate cancer: A case-control study | journal = Urologia | volume = 90 | issue = 4 | pages = 715–719 | date = November 2023 | pmid = 37606191 | doi = 10.1177/03915603231192736 }}</ref>