Histological changes of adrenal gland under conditions of immobilization stress on the background of hypothyroidism

Summary. The action of the stress factor, regardless of its origin, causes a chain of protective reactions of the body. Adrenal gland is a stress-sensitive organ, the development of adaptation mechanisms under these conditions can be characterized by its morphological state. The aim of the study – to investigate the features of histological changes in the adrenal glands of rats under the conditions of immobilization stress, which occurred on the background of experimental hypothyroidism. Materials and Methods. The experiment was conducted on 20 sexually mature white male rats. Hypothyroidism was modeled by daily per os injection using a probe of the pharmacopoeial mercazole thyreostatics at a dose of 25 mg/kg during the 21st day. Immobilization stress was modeled by tying rats in a supine position by 4 limbs without restricting head mobility for 3 hours. The study was conducted 2 hours later (anxiety stage) after the end of the stressor. Histological studies were carried out according to generally accepted methods. Results. Microscopic examination of the adrenal glands under conditions of immobilization stress revealed signs of destructive changes in the organ. Single blood-filled and dilated vessels were present. Cells with signs of destruction and swelling of the cytoplasm were determined. The presence of endocrinocytes with a small amount of lipid inclusions unevenly distributed in the cytoplasm of cells was characteristic. Microscopic studies of the adrenal glands 2 hours after the action of the stress factor on the background of hypothyroidism showed more significant changes in the structure of the organ. Perivascular edema was present. The connective tissue capsule was thickened. Single cells were necrotically altered and had pyknotic nuclei. Numerous endocrinocytes were poor in lipid inclusions, or completely devoid of them. In the medulla, there were destructively changed chromaffinocytes, with phenomena of edema and vacuolization of the cytoplasm. There were numerous blood vessels with blood-filled, dilated lumens. Conclusions. Under conditions of stress, destructive changes in the structure of the organ were established, which were characterized by engorgement of blood vessels and swelling of their walls, destruction of endocrinocytes of all zones. Under the conditions of the combined effect of immobilization stress with hypothyroidism, more significant changes in the structure of the organ were observed – reorganization of the vessel walls, thickening of the organ capsule, disorganization of the structural components of the stroma of the organ, and the presence of destructively and necrotically altered endocrinocytes

stress, adrenal gland, microscopic changes, hypothyroidism, endocrinocytes

https://doi.org/10.11603/bmbr.2706-6290.2022.4.13165

[1] Walker C-D. Anand KJS, Plotsky PM. Development of  the  hypothalamic-pituitary-adrenal  axis  and  the  stress response. Comprehensive Physiology. 2011: 237-70.

[2] Kanczkowski W, Sue M, Zacharowski K, Reincke M, Bornstein SR. The role of adrenal gland microenvironment in the HPA axis function and dysfunction during sepsis. Mol Cell Endocrinol. 2015;408: 241-8.

[3] Di Lorenzo M, Barra T, Rosati L, Valiante S, Capaldo A, De  Falco  M,  Laforgia  V.  Adrenal  gland  response  to endocrine disrupting chemicals in fishes, amphibians and reptiles: a comparative overview. General and Comparative Endocrinology,  2020;297:  113-550.  DOI:10.1016/j.ygcen. 2020.113550.

[4] Berger I, Werdermann M, Bornstein SR, Steenblock C. The adrenal gland in stress – Adaptation on a cellular level. Journal  of  Steroid  Biochemistry  and  Molecular  Biology. 2019;1(190):198-206. DOI:10.1016/j.jsbmb.2019.04.006.

[5] Tseilikman  V,  Komelkova  M,  Kondashevskaya  MV, Manukhina E, Downey HF, Chereshnev V, et al. A rat model of  post-traumatic  stress  syndrome  causes  phenotype-associated morphological changes and hypofunction of the adrenal gland. International Journal of Molecular Sciences. 2021;22(24): 13235. DOI:10.3390/ijms222413235.

[6] Bali  A,  Jaggi  AS.  Preclinical  experimental  stress studies:  protocols,  assessment  and  comparison.  Eur  J Pharmacol  2015;746:  282-92.  https://doi.org/https://doi.org/10.1016/j.ejphar.2014.10.017.

[7]  Brook ChGD, Clayton PE, R.S. Brown The adrenal cortex  and  its  disorders.  Brook's  clinical  pediatric endocrinology. 2010: 283-326.

[8] Wang  M,  Milic  M,  Gericke  A,  Mercieca  K,  Liu  H, Ruan Y, Jiang S, van Beers T, von Pein HD, Müller MB, Prokosch  V.  Chronic  social  defeat  stress  causes  retinal vascular  dysfunction.  Exp  Eye  Res.  2021;213:  108853. DOI:  10.1016/j.exer.2021.108853.  Epub  2021  Nov  18. PMID: 34800481.

[9] Zaki   SM, Abdelgawad FA, El-Shaarawy EAA, Radwan RAK, Aboul-Hoda BE. Stress-induced changes in the aged-rat adrenal cortex. Histological and histomorphometric study. Folia Morphol (Warsz). 2018;77(4): 629-641. DOI: 10.5603/FM.a2018.0035. Epub 2018 Apr 3. PMID: 29611160.

[10]  Kozhemyakin  YuM,  Hromov  OS,  Filonenko  MA, Sajfetdinova GA. Scientific and practical recommendations for  keeping  laboratory  animals  and  working  with  them. [Науково-практичні  рекомендації  з  утримання  лабора-торних тварин та роботи з ними] Kyiv: Interservis; 2017. Ukrainian.

[11] Isman CA. Methimazole-induced hypothyroidism in rats  ameliorates  oxidative  injury  in  experimental  colitis.  J Endocrinol. 2003;177(3): 471-6.

[12]  Argumedo GS, Sanz CR, Olguín HJ. Experimental models  of  developmental  hypothyroidism.  Horm  Metab Res.  2012;44(2):  79-85.  DOI:  10.1055/s-0031-1297941. Epub 2011 Dec 27. PMID: 22203441.

[13] Lyubovich ОYe, Klishch IM. Features of the cytokine profile of rats blood in thedynamics of immobilization stress on the background of hypothyroidism. [Особливості цитокінового профілю крові щурів в динаміці іммобілізаційного стресу на тлі гіпотиреозу] Bulletin of Problems in Biology and  Medicine-Вісник  проблем  біології  та  медицини. 2019;1(1): 140-4. Ukrainian.

[14] Horalskyi  LP,  Khomych  VT,  &  Kononskyi  OI. Fundamentals    of    histological    technique    and morphofunctionalmethods  of  research  in  normal  and pathology.  [Основи  гістологічної  техніки  і  морфофунк-ціональні методи досліджень у нормі та при патології]. Zhytomyr: Polissia; 2015. Ukrainian.

[15] Zhurakivska  OIa,  Zhurakivskyi  VM,  Dutchak  UM, Kulynych HB, Tkachuk YuL. [Morphofunctional changes in the adrenal glands in the early deadline of the development of  streptosotocin  diabetes  mellitus].  Klin  anatom  i  operat khirurhiia. 2019;2: 82-8. Ukrainian.

[16] Kniazevych-Chorna TV, Mykhailiuk IO, Rudiak OM, Tarasevych NR. [The functional state of the adrenal glands in  combination  with  their  morphological  restructuring  at different  stages  of  the  post-hypothermic  period].  Visn Vinnyts nats med univer. 2019;1(23): 41-5. DOI: 10.31393/reports-vnmedical-2019-23(1)-06.

[17] Gannouni  N,  Mhamdi  A,  El  May  M,  Tebourbi  O, Rhouma KB. Morphological changes of adrenal gland and heart tissue after varying duration of noise exposure in adult rat.  Noise  Health  2014;16:  416-21.  DOI:  10.4103/1463-1741.144424.