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Environmental Impact on the Hypothalamus–Pituitary Axis

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Environmental Endocrinology and Endocrine Disruptors

Part of the book series: Endocrinology ((ENDOCR))

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Abstract

The term endocrine-disrupting chemicals (EDCs) encloses several chemical compounds, mainly present in industrial products or in the environment as pollutants, capable of altering the homeostasis of the human body in different ways. Because of their intrinsic characteristics, EDCs present with complex pharmacokinetics with a noncanonical dose–response pattern and a frequent additive or synergistic way of action. The endocrine system is one of the main targets of these substances and of many other environmental factors (i.e., climate change, radiations) that can impact at different levels on each hypothalamus–pituitary–peripheral gland axis, leading to hormonal dysfunctions and infertility. The pituitary is also interested in the direct effect of EDCs, related to the development of tumors via their multiple actions on AHR/AIP pathways. In this chapter, we provide a review of the state of the art on the role of EDCs and environmental factors on pituitary function and tumorigenesis.

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References

  • Beckers A, Aaltonen LA, Daly AF, Karhu A. Familial isolated pituitary adenomas (FIPA) and the pituitary adenoma predisposition due to mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene. Endocr Rev. 2013; https://doi.org/10.1210/er.2012-1013.

  • Bellingham M, Fowler PA, MacDonald ES, Mandon-Pepin B, Cotinot C, Rhind S, … Evans NP. Timing of maternal exposure and foetal sex determine the effects of low-level chemical mixture exposure on the foetal neuroendocrine system in sheep. J Neuroendocrinol. 2016. https://doi.org/10.1111/jne.12444.

  • Binsiya TK, Sejian V, Bagath M, Krishnan G, Hyder I, Manimaran A, … Bhatta R. Significance of hypothalamic-pituitary-adrenal axis to adapt to climate change in livestock. Int Res J Agric Food Sci. 2017;2(1):1–20.

    Google Scholar 

  • Cannavò S, Ferraù F, Ragonese M, Curtò L, Torre ML, Magistri M, … Trimarchi F. Increased prevalence of acromegaly in a highly polluted area. Eur J Endocrinol. 2010;163(4):509–13. https://doi.org/10.1530/EJE-10-0465.

  • Cannavo S, Ferrau F, Ragonese M, Romeo PD, Torre ML, Puglisi S, … Trimarchi F. Increased frequency of the rs2066853 variant of aryl hydrocarbon receptor gene in patients with acromegaly. Clin Endocrinol. 2014;81(2):249–53. https://doi.org/10.1111/cen.12424.

  • Cannavo S, Ragonese M, Puglisi S, Romeo PD, Torre ML, Alibrandi A, … Ferrau F. Acromegaly is more severe in patients with AHR or AIP gene variants living in highly polluted areas. J Clin Endocrinol Metab. 2016;101(4):1872–9. https://doi.org/10.1210/jc.2015-4191.

  • Cao J, Patisaul HB, Petersen SL. Aryl hydrocarbon receptor activation in lactotropes and gonadotropes interferes with estradiol-dependent and -independent preprolactin, glycoprotein alpha and luteinizing hormone beta gene expression. Mol Cell Endocrinol. 2011; https://doi.org/10.1016/j.mce.2010.12.027.

  • Caserta D, Bordi G, Ciardo F, Marci R, La Rocca C, Tait S, … Moscarini M. The influence of endocrine disruptors in a selected population of infertile women. Gynecol Endocrinol. 2013. https://doi.org/10.3109/09513590.2012.758702.

  • Crisafulli S, Luxi N, Sultana J, Fontana A, Spagnolo F, Giuffrida G, et al. Global epidemiology of acromegaly: a systematic review and meta-analysis. Eur J Endocrinol. 2021; https://doi.org/10.1530/EJE-21-0216.

  • De Oliveira SK, Hoffmeister M, Gambaryan S, Müller-Esterl W, Guimaraes JA, Smolenski AP. Phosphodiesterase 2A forms a complex with the co-chaperone XAP2 and regulates nuclear translocation of the aryl hydrocarbon receptor. J Biol Chem. 2007; https://doi.org/10.1074/jbc.M610942200.

  • Denison MS, Pandini A, Nagy SR, Baldwin EP, Bonati L. Ligand binding and activation of the Ah receptor. Chem Biol Interact. 2002; https://doi.org/10.1016/S0009-2797(02)00063-7.

  • Diamanti-Kandarakis E, Bourguignon JP, Giudice LC, Hauser R, Prins GS, Soto AS, et al. Endocrine-disrupting chemicals: an Endocrine Society scientific statement. Endocr Rev. 2009;30(4):293–342.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dickerson SM, Guevara E, Woller MJ, Gore AC. Cell death mechanisms in GT1–7 GnRH cells exposed to polychlorinated biphenyls PCB74, PCB118, and PCB153. Toxicol Appl Pharmacol. 2009; https://doi.org/10.1016/j.taap.2009.04.001.

  • Dietrich C, Kaina B. The aryl hydrocarbon receptor (AhR) in the regulation of cell-cell contact and tumor growth. Carcinogenesis. 2010;31(8):1319–28. https://doi.org/10.1093/carcin/bgq028.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dirtu AC, Niessen SJM, Jorens PG, Covaci A. Organohalogenated contaminants in domestic cats’ plasma in relation to spontaneous acromegaly and type 2 diabetes mellitus: a clue for endocrine disruption in humans? Environ Int. 2013; https://doi.org/10.1016/j.envint.2013.04.004.

  • Dyson N. The regulation of E2F by pRB-family proteins. Genes Dev. 1998; https://doi.org/10.1101/gad.12.15.2245.

  • Elango A, Shepherd B, Chen TT. Effects of endocrine disrupters on the expression of growth hormone and prolactin mRNA in the rainbow trout pituitary. Gen Comp Endocrinol. 2006; https://doi.org/10.1016/j.ygcen.2005.08.003.

  • Eskenazi B, Ames J, Rauch S, Signorini S, Brambilla P, Mocarelli P, et al. Dioxin exposure associated with fecundability and infertility in mothers and daughters of Seveso, Italy. Hum Reprod. 2021; https://doi.org/10.1093/humrep/deaa324.

  • Ferraù F, Romeo PD, Puglisi S, Ragonese M, Spagnolo F, Salpietro C, … Cannavò S. GSTP1 gene methylation and AHR rs2066853 variant predict resistance to first generation somatostatin analogs in patients with acromegaly. J Endocrinol Invest. 2019. https://doi.org/10.1007/s40618-018-0988-8.

  • Formosa R, Borg J, Vassallo J. Aryl hydrocarbon receptor (AHR) is a potential tumour suppressor in pituitary adenomas. Endocr Relat Cancer. 2017a; https://doi.org/10.1530/ERC-17-0112.

  • Formosa R, Borg J, Vassallo J. The complex biology of the aryl hydrocarbon receptor and its role in the pituitary gland. Horm Cancer. 2017b;8(4):197–210.

    Article  CAS  PubMed  Google Scholar 

  • Fortunati N, Guaraldi F, Zunino V, Penner F, D’Angelo V, Zenga F, … Arvat E. Effects of environmental pollutants on signaling pathways in rat pituitary GH3 adenoma cells. Environ Res. 2017;158:660–8. https://doi.org/10.1016/j.envres.2017.07.015.

  • Giesy JP, Kannan K. Dioxin-like and non-dioxin-like toxic effects of polychlorinated biphenyls (PCBs): implications for risk assessment. Crit Rev Toxicol. 1998; https://doi.org/10.1080/10408449891344263.

  • Gore AC. Neuroendocrine targets of endocrine disruptors. Hormones. 2010;9(1):16–27. https://doi.org/10.14310/horm.2002.1249.

    Article  PubMed  Google Scholar 

  • Gore AC, Walker DM, Zama AM, Armenti AE, Uzumcu M. Early life exposure to endocrine-disrupting chemicals causes lifelong molecular reprogramming of the hypothalamus and premature reproductive aging. Mol Endocrinol. 2011; https://doi.org/10.1210/me.2011-1210.

  • Gould JC, Cooper KR, Scanes CG. Effects of polychlorinated biphenyl mixtures and three specific congeners on growth and circulating growth-related hormones. Gen Comp Endocrinol. 1997; https://doi.org/10.1006/gcen.1996.6868.

  • Harper PA, Wong JMY, Lam MSM, Okey AB. Polymorphisms in the human AH receptor. Chem Biol Interact. 2002; https://doi.org/10.1016/S0009-2797(02)00071-6.

  • Hattori Y, Takeda T, Nakamura A, Nishida K, Shioji Y, Fukumitsu H, … Ishii Y. The aryl hydrocarbon receptor is indispensable for dioxin-induced defects in sexually-dimorphic behaviors due to the reduction in fetal steroidogenesis of the pituitary-gonadal axis in rats. Biochem Pharmacol. 2018. https://doi.org/10.1016/j.bcp.2018.05.008.

  • Heliövaara E, Raitila A, Launonen V, Paetau A, Arola J, Lehtonen H, … Karhu A. The expression of AIP-related molecules in elucidation of cellular pathways in pituitary adenomas. Am J Pathol. 2009. https://doi.org/10.2353/ajpath.2009.081131.

  • Interdonato M, Pizzino G, Bitto A, Galfo F, Irrera N, et al. Cadmium delays puberty onset and testis growth in adolescents. Clin Endocrinol. 2015; https://doi.org/10.1111/cen.12704.

  • Jaffrain-Rea ML, Angelini M, Gargano D, Tichomirowa MA, Daly AF, Vanbellinghen JF, … Beckers A. Expression of aryl hydrocarbon receptor (AHR) and AHR-interacting protein in pituitary adenomas: pathological and clinical implications. Endocr Relat Cancer. 2009. https://doi.org/10.1677/ERC-09-0094.

  • Khan MA, Hansen LG. Ortho-substituted polychlorinated biphenyl (PCB) congeners (95 or 101) decrease pituitary response to thyrotropin releasing hormone. Toxicol Lett. 2003; https://doi.org/10.1016/S0378-4274(03)00203-0.

  • Kolluri SK, Weiss C, Koff A, Göttlicher M. p27(Kip1) induction and inhibition of proliferation by the intracellular Ah receptor in developing thymus and hepatoma cells. Genes Dev. 1999; https://doi.org/10.1101/gad.13.13.1742.

  • Laks DR. Assessment of chronic mercury exposure within the U.S. population, National Health and Nutrition Examination Survey, 1999–2006. Biometals. 2009; https://doi.org/10.1007/s10534-009-9261-0.

  • Lauretta R, Sansone A, Sansone M, Romanelli F, Appetecchia M. Endocrine disrupting chemicals: effects on endocrine glands. Front Endocrinol. 2019;10:1–7. https://doi.org/10.3389/fendo.2019.00178.

    Article  Google Scholar 

  • Lecoq AL, Viengchareun S, Hage M, Bouligand J, Young J, Boutron A, … Kamenicky P. AIP mutations impair AhR signalling in pituitary adenoma patients fibroblasts and in GH3 cells. Endocr Relat Cancer. 2016. https://doi.org/10.1530/ERC-16-0041.

  • Lee S, Kim C, Youn H, Choi K. Thyroid hormone disrupting potentials of bisphenol A and its analogues – in vitro comparison study employing rat pituitary (GH3) and thyroid follicular (FRTL-5) cells. Toxicol In Vitro. 2017; https://doi.org/10.1016/j.tiv.2017.02.004.

  • Lloyd C, Grossman A. The AIP (aryl hydrocarbon receptor-interacting protein) gene and its relation to the pathogenesis of pituitary adenomas. Endocrine. 2014; https://doi.org/10.1007/s12020-013-0125-6.

  • Long M, Ghisari M, Bonefeld-Jørgensen EC. Effects of perfluoroalkyl acids on the function of the thyroid hormone and the aryl hydrocarbon receptor. Environ Sci Pollut Res. 2013; https://doi.org/10.1007/s11356-013-1628-7.

  • Melo MC, Andersson E, Fjelldal PG, Bogerd J, França LR, Taranger GL, Schulz RW. Salinity and photoperiod modulate pubertal development in Atlantic salmon (Salmo salar). J Endocrinol. 2014;220(3):319–32. https://doi.org/10.1530/JOE-13-0240.

    Article  CAS  PubMed  Google Scholar 

  • Merlo E, Podratz PL, Sena GC, De Araújo JFP, Lima LCF, Alves ISS, … Graceli JB. The environmental pollutant tributyltin chloride disrupts the hypothalamic-pituitary-adrenal axis at different levels in female rats. Endocrinology. 2016. https://doi.org/10.1210/en.2015-1896.

  • Molon-Noblot S, Laroque P, Coleman JB, Hoe CM, Keenan KP. The effects of ad libitum overfeeding and moderate and marked dietary restriction on age-related spontaneous pituitary gland pathology in Sprague-Dawley rats. Toxicol Pathol. 2003; https://doi.org/10.1080/01926230309763.

  • Monneret C. What is an endocrine disruptor? C R Biol. 2017; https://doi.org/10.1016/j.crvi.2017.07.004.

  • Moran TB, Brannick KE, Raetzman LT. Aryl-hydrocarbon receptor activity modulates prolactin expression in the pituitary. Toxicol Appl Pharmacol. 2012; https://doi.org/10.1016/j.taap.2012.08.026.

  • Niazi A, Niazi S. Endocrine effects of Fukushima: radiation-induced endocrinopathy. Indian J Endocrinol Metab. 2011; https://doi.org/10.4103/2230-8210.81936.

  • Norris DO, Donahue S, Dores RM, Lee JK, Maldonado TA, Ruth T, Woodling JD. Impaired adrenocortical response to stress by brown trout, Salmo trutta, living in metal-contaminated waters of the Eagle River, Colorado. Gen Comp Endocrinol. 1999;113:1–8.

    Article  CAS  PubMed  Google Scholar 

  • Pesatori AC, Baccarelli A, Consonni D, Lania A, Beck-Peccoz P, Bertazzi PA, Spada A. Aryl hydrocarbon receptor-interacting protein and pituitary adenomas: a population-based study on subjects exposed to dioxin after the Seveso, Italy, accident. Eur J Endocrinol. 2008; https://doi.org/10.1530/EJE-08-0593.

  • Pillai A, Laxmi Priya PN, Gupta S. Effects of combined exposure to lead and cadmium on pituitary membrane of female rats. Arch Toxicol. 2002; https://doi.org/10.1007/s00204-002-0399-6.

  • Pillai A, Priya L, Gupta S. Effects of combined exposure to lead and cadmium on the hypothalamic-pituitary axis function in proestrous rats. Food Chem Toxicol. 2003; https://doi.org/10.1016/S0278-6915(02)00247-8.

  • Pomeraniec IJ, Taylor DG, Cohen-Inbar O, Xu Z, Lee Vance M, Sheehan JP. Radiation dose to neuroanatomical structures of pituitary adenomas and the effect of Gamma Knife radiosurgery on pituitary function. J Neurosurg. 2019; https://doi.org/10.3171/2019.1.jns182296.

  • Preston DL. Tumors of the nervous system and pituitary gland associated with atomic bomb radiation exposure. J Natl Cancer Inst. 2002; https://doi.org/10.1093/jnci/94.20.1555.

  • Raggi F, Russo D, Urbani C, Sardella C, Manetti L, Cappellani D, … Bogazzi F. Divergent effects of dioxin- or non-dioxin-like polychlorinated biphenyls on the apoptosis of primary cell culture from the mouse dioxin pituitary gland. PLoS One. 2016. https://doi.org/10.1371/journal.pone.0146729.

  • Rattan S, Zhou C, Chiang C, Mahalingam S, Brehm E, Flaws JA. Exposure to endocrine disruptors during adulthood: consequences for female fertility. J Endocrinol. 2017; https://doi.org/10.1530/JOE-17-0023.

  • Reimondo G, Puglisi S, Zaggia B, Basile V, Saba L, Perotti P, … Terzolo M. Effects of mitotane on the hypothalamic-pituitary-adrenal axis in patients with adrenocortical carcinoma. Eur J Endocrinol. 2017. https://doi.org/10.1530/EJE-17-0452.

  • Rowlands JC, Gustafsson JÅ. Aryl hydrocarbon receptor-mediated signal transduction. Crit Rev Toxicol. 1997; https://doi.org/10.3109/10408449709021615.

  • Schug TT, Janesick A, Blumberg B, Heindel JJ. Endocrine disrupting chemicals and disease susceptibility. J Steroid Biochem Mol Biol. 2011; https://doi.org/10.1016/j.jsbmb.2011.08.007.

  • Schug T, Johnson AF, Birnbaum LS, Colborn T, Guillette LJ, Crews DP, et al. Minireview. Endocrine disruptors: past lessons and future directions. Mol Endocrinol. 2016; https://doi.org/10.1210/me.2016-1096.

  • Shanle EK, Xu W. Endocrine disrupting chemicals targeting estrogen receptor signaling: identification and mechanisms of action. Chem Res Toxicol. 2011; https://doi.org/10.1021/tx100231n.

  • Solomon-Lane TK, Hofmann HA. Early-life social environment alters juvenile behavior and neuroendocrine function in a highly social cichlid fish. Horm Behav. 2019; https://doi.org/10.1016/j.yhbeh.2019.06.016.

  • Stoker TE, Perreault SD, Bremser K, Marshall RS, Murr A, Cooper RL. Acute exposure to molinate alters neuroendocrine control of ovulation in the rat. Toxicol Sci. 2005; https://doi.org/10.1093/toxsci/kfi064.

  • Takeda T, Taura J, Hattori Y, Ishii Y, Yamada H. Dioxin-induced retardation of development through a reduction in the expression of pituitary hormones and possible involvement of an aryl hydrocarbon receptor in this defect: a comparative study using two strains of mice with different sensitivities to dioxin. Toxicol Appl Pharmacol. 2014. https://doi.org/10.1016/j.taap.2014.04.022.

  • Tapella L, Sesta A, Cassarino MF, Zunino V, Catalano MG, Pecori Giraldi F. Benzene and 2-ethyl-phthalate induce proliferation in normal rat pituitary cells. Pituitary. 2017;20(3):311–8. https://doi.org/10.1007/s11102-016-0777-3.

    Article  CAS  PubMed  Google Scholar 

  • Trivellin G, Korbonits M. AIP and its interacting partners. J Endocrinol. 2011; https://doi.org/10.1530/JOE-11-0054.

  • Tuominen I, Heliövaara E, Raitila A, Rautiainen MR, Mehine M, Katainen R, … Karhu A. AIP inactivation leads to pituitary tumorigenesis through defective Gαi-cAMP signaling. Oncogene. 2015. https://doi.org/10.1038/onc.2014.50.

  • Van Cauwenbergh O, Di Serafino A, Tytgat A, Soubry A. Transgenerational epigenetic effects from male exposure to endocrine-disrupting compounds: a systematic review on research in mammals. Clin Epigenet. 2020; https://doi.org/10.1186/s13148-020-00845-1.

  • van Iersel L, van Santen H, Potter B, Li Z, Conklin H, Srivastava DK, … Merchant T. SAT-457 hypothalamic-pituitary disorders after conformal radiation therapy for childhood and young adult low-grade glioma or ependymoma. J Endocr Soc. 2019. https://doi.org/10.1210/js.2019-sat-457.

  • West C, Foster DL, Evans NP, Robinson J, Padmanabhan V. Intra-follicular activin availability is altered in prenatally-androgenized lambs. Mol Cell Endocrinol. 2001; https://doi.org/10.1016/S0303-7207(01)00632-3.

  • Yang X, Liu D, Murray TJ, Mitchell GC, Hesterman EV, Karchner SI, … Sherr DH. The aryl hydrocarbon receptor constitutively represses c-myc transcription in human mammary tumor cells. Oncogene. 2005. https://doi.org/10.1038/sj.onc.1208938.

  • Zoeller RT, Tan SW, Tyl RW. General background on the hypothalamic-pituitary-thyroid (HPT) axis. Crit Rev Toxicol. 2007; https://doi.org/10.1080/10408440601123446.

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Acknowledgments

This chapter has been supported by the following grants: grant of the Ministry of Health (Progetto Ordinario Ricerca Finalizzata RF-2013-02356201) of the Italian government; grant (Progetto Rilevante di Interesse Nazionale, PRIN 2017): identification of new biomarkers and clinical determinants for management improvement of patients with pituitary tumor-related syndromes (code: PRIN 2017S55RXB) of the Italian government; and Industrial PhD Course 2017 (EU P.O.N. – Progetto Operativo Nazionale 2014–2020, code: DOT1314588).

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Authors and Affiliations

  1. Department of Human Pathology of Adulthood and Childhood, University of Messina, Sicily, Italy

    Giuseppe Giuffrida, Francesco Ferraù, Marta Ragonese & Salvatore Cannavò

  2. Endocrine Unit, “G. Martino” University Hospital of Messina, Sicily, Italy

    Giuseppe Giuffrida, Francesco Ferraù, Marta Ragonese & Salvatore Cannavò

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  1. Giuseppe Giuffrida
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  2. Francesco Ferraù
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  3. Marta Ragonese
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  4. Salvatore Cannavò
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Correspondence to Salvatore Cannavò .

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Editors and Affiliations

  1. Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Unità di Andrologia e Medicina della Riproduzione e della Sessualità Maschile e Femminile (FERTISEXCARES), Università Federico II di Napoli, Naples, Italy

    Rosario Pivonello

  2. Medical School, National and Kapodistrian University of Athens, Athens, Greece

    Evanthia Diamanti-Kandarakis

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Giuffrida, G., Ferraù, F., Ragonese, M., Cannavò, S. (2023). Environmental Impact on the Hypothalamus–Pituitary Axis. In: Pivonello, R., Diamanti-Kandarakis, E. (eds) Environmental Endocrinology and Endocrine Disruptors . Endocrinology. Springer, Cham. https://doi.org/10.1007/978-3-030-39044-0_2

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