Abstract
The endocrine system represents multiple cell signaling systems that regulate metabolic processes and maintain body homeostasis in the fetus and adult. The endocrine system regulates many biologic processes including development, growth, reproduction, gastrointestinal, cardiovascular, and renal systems, among others, as well as the response of the body to acute and chronic stress. Anatomically, the endocrine glands are distinct collections of specialized cells that respond to both internal and external environmental signals and produce and secrete chemical mediators or hormones, which generally fall into three categories: polypeptides, steroids, and tyrosine derivatives. Regulation of the endocrine glands is the result of both positive and negative feedback loops, which allow for both rapid and sustained changes in hormone production and secretion. Xenobiotics and environmental compounds have the potential to perturb the function of endocrine organs. Toxic effects of xenobiotics on the endocrine organs can result from either the stimulation or inhibition of hormone production and secretion. The proliferative lesions may be functional or nonfunctional. Gross and microscopic histopathology is used to identify proliferative lesions in the endocrine glands. In this chapter, we examine the main endocrine organs: pituitary gland, thyroid and parathyroid gland, adrenal gland, endocrine pancreas, and the pineal gland. Functional anatomy and physiology, spontaneous or background lesions, and xenobiotic-related proliferative and nonproliferative lesions for each organ are discussed.
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References
Akana SF, Shinsako J, Dallman MF (1983) Relationships among adrenal weight, corticosterone, and stimulated adrenocorticotropin levels in rats. Endocrinology 113(6):2226–2231. https://doi.org/10.1210/endo-113-6-2226
Al Zubaidy AJ, Malinowski W (1984) Spontaneous pineal body tumours (pinealomas) in Wistar rats; a histological and ultrastructural study. Lab Anim 18(3):224–229. https://doi.org/10.1258/002367784780958295
Bedrak E, Chap Z, Brown R (1983) Age-related changes in the hypothalamic-pituitary-testicular function of the rat. Exp Gerontol 18(2):95–104
Brandli-Baiocco A, Balme E, Bruder M, Chandra S, Hellmann J, Hoenerhoff MJ, Kambara T, Landes C, Lenz B, Mense M, Rittinghausen S, Satoh H, Schorsch F, Seeliger F, Tanaka T, Tsuchitani M, Wojcinski Z, Rosol TJ (2018) Nonproliferative and proliferative lesions of the rat and mouse endocrine system. J Toxicol Pathol 31(3 Suppl):1S–95S. https://doi.org/10.1293/tox.31.1S
Byrd RA, Sorden SD, Ryan T, Pienkowski T, LaRock R, Quander R, Wijsman JA, Smith HW, Blackbourne JL, Rosol TJ, Long GG, Martin JA, Vahle JL (2015) Chronic toxicity and carcinogenicity studies of the long-acting GLP-1 receptor agonist dulaglutide in rodents. Endocrinology 156(7):2417–2428. https://doi.org/10.1210/en.2014-1722
Capen CC, Martin SL (1989) Mechanisms that lead to disease of the endocrine system in animals. Toxicol Pathol 17(2):234–249. https://doi.org/10.1177/019262338901700202
Capen CC, Rosol TJ (1989) Recent advances in the structure and function of the parathyroid gland in animals and the effects of xenobiotics. Toxicol Pathol 17(2):333–345. https://doi.org/10.1177/019262338901700210
Chamanza R, Marxfeld HA, Blanco AI, Naylor SW, Bradley AE (2010) Incidences and range of spontaneous findings in control cynomolgus monkeys (Macaca fascicularis) used in toxicity studies. Toxicol Pathol 38(4):642–657. https://doi.org/10.1177/0192623310368981
Chandra S, Hoenerhoff MJ, Peterson R (2013) Endocrine glands. In: Sahota PS, Popp JA, Hardisty JF, Gopinath C (eds) Toxicologic pathology: nonclinical safety assessment. CRC Press. Boca Raton, Florida
Chapin RE, Creasy DM (2012) Assessment of circulating hormones in regulatory toxicity studies II. Male reproductive hormones. Toxicol Pathol 40(7):1063–1078. https://doi.org/10.1177/0192623312443321
Chen HJ (1984) Age and sex difference in serum and pituitary thyrotropin concentrations in the rat: influence by pituitary adenoma. Exp Gerontol 19(1):1–6
Ennulat D, Walker D, Clemo F, Magid-Slav M, Ledieu D, Graham M, Botts S, Boone L (2010) Effects of hepatic drug-metabolizing enzyme induction on clinical pathology parameters in animals and man. Toxicol Pathol 38(5):810–828. https://doi.org/10.1177/0192623310374332
Everds NE, Snyder PW, Bailey KL, Bolon B, Creasy DM, Foley GL, Rosol TJ, Sellers T (2013) Interpreting stress responses during routine toxicity studies: a review of the biology, impact, and assessment. Toxicol Pathol 41(4):560–614. https://doi.org/10.1177/0192623312466452
Félix NM, Goy-Thollot I, Walton RS, Gil SA, Mateus LM, Matos AS, Niza MM (2016) Effects of etomidate in the adrenal and cytokine responses to hemorrhagic shock in rats. Eur J Inflamm 14(3):147–161. https://doi.org/10.1177/1721727x16677604
Gaskill CL, Burton SA, Gelens HC, Ihle SL, Miller JB, Shaw DH, Brimacombe MB, Cribb AE (1999) Effects of phenobarbital treatment on serum thyroxine and thyroid-stimulating hormone concentrations in epileptic dogs. J Am Vet Med Assoc 215(4):489–496
Goedegebuure SA, Hazewinkel HA (1986) Morphological findings in young dogs chronically fed a diet containing excess calcium. Vet Pathol 23(5):594–605. https://doi.org/10.1177/030098588602300508
Greaves P (2012) Histopathology of preclinical toxicity studies: interpretation and relevance in drug safety studies. 4th edn. Elsevier/AP, Amsterdam/Boston
Harvey PW (2016) Adrenocortical endocrine disruption. J Steroid Biochem Mol Biol 155(Pt B):199–206. https://doi.org/10.1016/j.jsbmb.2014.10.009
Hatakeyama S, Tuchweber B, Blascheck JA, Garg BD, Kovacs K (1970) Parathyroid cyst formation induced by dihydrotachysterol and calcium acetate. An electron microscopic study. Endocrinol Jpn 17(5):355–358. passim
Hood A, Allen ML, Liu Y, Liu J, Klaassen CD (2003) Induction of T(4) UDP-GT activity, serum thyroid stimulating hormone, and thyroid follicular cell proliferation in mice treated with microsomal enzyme inducers. Toxicol Appl Pharmacol 188(1):6–13
Inomata A, Sasano H (2015) Practical approaches for evaluating adrenal toxicity in nonclinical safety assessment. J Toxicol Pathol 28(3):125–132. https://doi.org/10.1293/tox.2015-0025
Itakura C, Iida M, Goto M (1977) Renal secondary hyperparathyroidism in aged Sprague-Dawley rats. Vet Pathol 14(5):463–469. https://doi.org/10.1177/030098587701400505
Krinke GJ, Kaufmann W, Mahrous AT, Schaetti P (2000) Morphologic characterization of spontaneous nervous system tumors in mice and rats. Toxicol Pathol 28(1):178–192. https://doi.org/10.1177/019262330002800123
Laast VA, Larsen T, Allison N, Hoenerhoff MJ, Boorman GA (2014) Distinguishing cystic degeneration from other aging lesions in the adrenal cortex of Sprague-Dawley rats. Toxicol Pathol 42(5):823–829. https://doi.org/10.1177/0192623313502258
Ledingham IM, Watt I (1983) Influence of sedation on mortality in critically ill multiple trauma patients. Lancet 1(8336):1270
Martini FH, Nath JL, Bartholomew EF (2012) The endocrine system. In: Fundamentals of anatomy and physiology. Pearson Education, Inc., London
McCance KL, Huether SE (2010) Pathophysiology: the biologic basis for disease in adults and children, vol 6. Mosby, St Louis
McInnes EF (2012) Wistar and Sprague-Dawley rats. In: EF MI (ed) Background lesions in laboratory animals: a color atlas. Elsevier Health Sciences
Mitani F (2014) Functional zonation of the rat adrenal cortex: the development and maintenance. Proc Jpn Acad Ser B Phys Biol Sci 90(5):163–183
Mohamed-Ali V, Pinkney JH, Coppack SW (1998) Adipose tissue as an endocrine and paracrine organ. Int J Obes Relat Metab Disord 22(12):1145–1158
Rosol TJ (2013) On-target effects of GLP-1 receptor agonists on thyroid C-cells in rats and mice. Toxicol Pathol 41(2):303–309. https://doi.org/10.1177/0192623312472402
Rosol TJ, Yarrington JT, Latendresse J, Capen CC (2001) Adrenal gland: structure, function, and mechanisms of toxicity. Toxicol Pathol 29(1):41–48. https://doi.org/10.1080/019262301301418847
Rosol TJ, Delellis RA, Harvey PW, Sutcliffe C (2013) Endocrine system. In: Haschek WM, Rousseaux CG, Wallig MA, Bolon B, Ochoa R, Mahler BW (eds) Haschek and Rousseaux's handbook of toxicologic pathology, 3rd edn. Academic Press, Amsterdam/Boston, pp 3 volumes (xxxvi, 2963 pages)
Seely JC, Hildebrandt PK (1990) Parathyroid gland. In: Boorman GA, Eustis SL, Elwell MR, Montgomery CAJ, MacKenzie WF (eds) Pathology of the Fischer rat: reference and atlas. Academic Press, San Diego, p xvi. 580 p
Stanislaus D, Andersson H, Chapin R, Creasy D, Ferguson D, Gilbert M, Rosol TJ, Boyce RW, Wood CE (2012) Society of toxicologic pathology position paper: review series: assessment of circulating hormones in nonclinical toxicity studies: general concepts and considerations. Toxicol Pathol 40(6):943–950. https://doi.org/10.1177/0192623312444622
Steiner DJ, Kim A, Miller K, Hara M (2010) Pancreatic islet plasticity: interspecies comparison of islet architecture and composition. Islets 2(3):135–145
Swindle MM1, Makin A, Herron AJ, Clubb FJ Jr, Frazier KS (2011) Swine as models in biomedical research and toxicology testing. Vet Pathol. 2012 Mar;49(2):344–356. https://doi.org/10.1177/0300985811402846. Epub 2011 Mar 25.
Szabo S, Lippe IT (1989) Adrenal gland: chemically induced structural and functional changes in the cortex. Toxicol Pathol 17(2):317–329. https://doi.org/10.1177/019262338901700208
Theuring F, Gotz W, Balling R, Korf HW, Schulze F, Herken R, Gruss P (1990) Tumorigenesis and eye abnormalities in transgenic mice expressing MSV-SV40 large T-antigen. Oncogene 5(2):225–232
Tischler AS, Powers JF, Downing JC, Riseberg JC, Shahsavari M, Ziar J, McClain RM (1996) Vitamin D3, lactose, and xylitol stimulate chromaffin cell proliferation in the rat adrenal medulla. Toxicol Appl Pharmacol 140(1):115–123. https://doi.org/10.1006/taap.1996.0204
Treumann S, Buesen R, Groters S, Eichler JO, van Ravenzwaay B (2015) Occurrence of pineal gland tumors in combined chronic toxicity/carcinogenicity studies in Wistar rats. Toxicol Pathol 43(6):838–843. https://doi.org/10.1177/0192623315572700
Tsuchitani M, Sato J, Kokoshima H (2016) A comparison of the anatomical structure of the pancreas in experimental animals. J Toxicol Pathol 29(3):147–154. https://doi.org/10.1293/tox.2016-0016
Vahle JL, Byrd RA, Blackbourne JL, Martin JA, Sorden SD, Ryan T, Pienkowski T, Wijsman JA, Smith HW, Rosol TJ (2015) Effects of dulaglutide on thyroid C cells and serum calcitonin in male monkeys. Endocrinology 156(7):2409–2416. https://doi.org/10.1210/en.2014-1717
Wieczorek G, Pospischil A, Perentes E (1998) A comparative immunohistochemical study of pancreatic islets in laboratory animals (rats, dogs, minipigs, nonhuman primates). Exp Toxicol Pathol 50(3):151–172. https://doi.org/10.1016/S0940-2993(98)80078-X
Zabka TS, Fielden MR, Garrido R, Tao J, Fretland AJ, Fretland JL, Albassam MA, Singer T, Kolaja KL (2011) Characterization of xenobiotic-induced hepatocellular enzyme induction in rats: anticipated thyroid effects and unique pituitary gland findings. Toxicol Pathol 39(4):664–677. https://doi.org/10.1177/0192623311406934
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Walling, B.E., Rosol, T.J. (2019). Pathology of the Endocrine System. In: Steinbach, T., Patrick, D., Cosenza, M. (eds) Toxicologic Pathology for Non-Pathologists. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9777-0_13
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