Preview

South Russian Journal of Cancer

Advanced search

Changes in pathophysiology of tumor growth and functional activity of the hypothalamic-pituitary-thyroid axis in rats of both sexes with the development of Guerin's carcinoma on the background of hypothyroidism

https://doi.org/10.37748/2686-9039-2022-3-4-3

Abstract

Purpose of the study. Was to analyze changes in pathophysiological parameters of transplantable tumor growth and functional activity of the hypothalamic-pituitary-thyroid axis (HPT) in rats of both sexes with Guerin's carcinoma in presence of induced hypothyroidism.

Materials and methods. The dynamics of tumor growth and average life span were assessed in white alley rats of both sexes with Guerins carcinoma transplanted subcutaneously on the background of thyreostatic induced hypothyroidism. RIA (radioimmune assay) and ELISA (enzyme-linked immunosorbent assay) methods were used to determine levels of thyroid hormones in the blood and thyroid and tumor samples, and thyrotropin-releasing hormone (TRH) in the hypothalamus, as well as TSH in the pituitary gland. The experiment included 2 control groups: animals of both sexes with hypothyroidism (control group 1, number of rodents = 15) and animals with subcutaneously transplanted Guerin's carcinoma without hypothyroidism (control group 2, number of rodents = 15).

Results. Hypothyroidism in female rats inhibited the tumor growth and improved median survival by 1.8 times (p < 0.05). No such effect was observed in males of the main group. Levels of regulatory peptides of the hypothalamus and pituitary gland declined in females of the main group, while levels of TSH in the pituitary gland in males increased, despite a decrease in TRH by 3.5 times. TSH levels decreased in the thyroid and blood of animals of both sexes; however, a decrease in levels of total and free circulating thyroxine (T4 and FT4) by 1.6 times and by 2.8 times was found in the tumor, respectively; samples of Guerin's carcinoma in males of the main group remained saturated with T4 and FT4 as well as and in control group rodents without induced hypothyroidism.

Conclusions. The gender differences in the pathophysiology of the tumor development in presence of hypothyroidism, as well as changes in the functional activity of the HPT axis in experimental animals revealed in this study can probably be associated with sex hormones, which requires further study of the hypothalamic-pituitary-gonadal (HPG) axis and steroid hormones in peripheral organs and tumor samples. 

About the Authors

E. M. Frantsiyants
National Medical Research Centre for Oncology
Russian Federation

Elena M. Frantsiyants - Dr. Sci. (Biol.), professor, deputy general director for science, 

Rostov-on-Don

SPIN: 9427-9928,

AuthorID: 462868,

ResearcherID: Y-1491-2018,

Scopus Author ID: 55890047700



V. A. Bandovkina
National Medical Research Centre for Oncology
Russian Federation

Valeriya A. Bandovkina - Dr. Sci. (Biol.), senior researcher of the laboratory for the study of pathogenesis of malignant tumors,

Rostov-on-Don

SPIN: 8806-2641,

AuthorID: 696989



I. V. Kaplieva
National Medical Research Centre for Oncology
Russian Federation

Irina V. Kaplieva - Dr. Sci. (Med.), senior researcher of the laboratory for the study of pathogenesis of malignant tumors, 

Rostov-on-Don

SPIN: 5047-1541,

AuthorID: 734116 



E. I. Surikova
National Medical Research Centre for Oncology
Russian Federation

Ekaterina I. Surikova - Cand. Sci. (Biol.), senior researcher of the laboratory for the study of pathogenesis of malignant tumors, 

Rostov-on-Don

SPIN: 2401-4115,

AuthorID: 301537 



I. V. Neskubina
National Medical Research Centre for Oncology
Russian Federation

Irina V. Neskubina - Cand. Sci. (Biol.), senior researcher at the laboratory for the study of the pathogenesis of malignant tumors, 

Rostov-on-Don

SPIN: 3581-8531,

AuthorID: 794688



Yu. A. Pogorelova
National Medical Research Centre for Oncology
Russian Federation

Yuliya A. Pogorelova - Cand. Sci. (Biol.), senior researcher at laboratory of malignant tumor pathogenesis study,

Rostov-on-Don

 SPIN: 2168-8737,

AuthorID: 558241



L. K. Trepitaki
National Medical Research Centre for Oncology
Russian Federation

Lidiya K. Trepitaki - researcher at the laboratory for the study of pathogenesis of malignant tumors,

Rostov-on-Don

SPIN: 2052-1248,

AuthorID: 734359



N. D. Cheryarina
National Medical Research Centre for Oncology
Russian Federation

Natalya D. Cheryarina - laboratory assistant at the laboratory for the study of the pathogenesis of malignant tumors,

Rostov-on-Don

SPIN: 2189-3404,

AuthorID: 558243



L. A. Nemashkalova
National Medical Research Centre for Oncology
Russian Federation

Lyudmila A. Nemashkalova - researcher at the laboratory for the study of the pathogenesis of malignant tumors, 

Rostov-on-Don

SPIN: 1355-8652,

AuthorID: 734146



A. Yu. Arakelova
National Medical Research Centre for Oncology
Russian Federation

Alina Yu. Arakelova - PhD student of the department of abdominal oncology No. 1, 

Rostov-on-Don



References

1. Barr CE, Njoku K, Hotchkies L, Ryan NAJ, Wan YL, Davies DA, et al. Does Clinical and Biochemical Thyroid Dysfunction Impact on Endometrial Cancer Survival Outcomes? A Prospective Database Study. Cancers (Basel). 2021 Oct 29;13(21):5444. https://doi.org/10.3390/cancers13215444

2. Giammanco M, Di Liegro CM, Schiera G, Di Liegro I. Genomic and Non-Genomic Mechanisms of Action of Thyroid Hormones and Their Catabolite 3,5-Diiodo-L-Thyronine in Mammals. Int J Mol Sci. 2020 Jun 10;21(11):E4140. https://doi.org/10.3390/ijms21114140

3. Shahid MA, Ashraf MA, Sharma S. Physiology, Thyroid Hormone. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan. 2022 May 8.

4. Baldini E, Lauro A, Tripodi D, Pironi D, Amabile MI, Ferent IC, et al. Thyroid Diseases and Breast Cancer. J Pers Med. 2022 Jan 25;12(2):156. https://doi.org/10.3390/jpm12020156

5. Anguiano B, Montes de Oca C, Delgado-González E, Aceves C. Prostate gland as a target organ of thyroid hormones: advances and controversies. Endocr Connect. 2022 Feb 14;11(2):e210581. https://doi.org/10.1530/EC-21-0581

6. Wilson SA, Stem LA, Bruehlman RD. Hypothyroidism: Diagnosis and Treatment. Am Fam Physician. 2021 May 15;103(10):605– 613. https://www.aafp.org/afp/2021/0515/p605.html

7. Planck T, Hedberg F, Calissendorff J, Nilsson A. Liothyronine Use in Hypothyroidism and its Effects on Cancer and Mortality. Thyroid. 2021 May;31(5):732–739. https://doi.org/10.1089/thy.2020.0388

8. Tran TVT, Kitahara CM, de Vathaire F, Boutron-Ruault MC, Journy N. Thyroid dysfunction and cancer incidence: a systematic review and meta-analysis. Endocr Relat Cancer. 2020 Apr;27(4):245–259. https://doi.org/10.1530/ERC-19-0417

9. Xu L, Leng C, Chen L, Dong H, Chen Y, Chen X. Hypothyroidism is a predictive factor of superior antitumour efficacy of programmed death 1 inhibitors in hepatocellular carcinoma. Int J Cancer. 2022 Feb 1;150(3):472–481. https://doi.org/10.1002/ijc.33813

10. Huang CH, Wei JCC, Chien TC, Kuo CW, Lin SH, Su YC, et al. Risk of Breast Cancer in Females With Hypothyroidism: A Nationwide, Population-Based, Cohort Study. Endocr Pract. 2021 Apr;27(4):298–305. https://doi.org/10.1016/j.eprac.2020.09.007

11. Kim EY, Chang Y, Lee KH, Yun JS, Park YL, Park CH, et al. Serum concentration of thyroid hormones in abnormal and euthyroid ranges and breast cancer risk: A cohort study. Int J Cancer. 2019 Dec 15;145(12):3257–3266. https://doi.org/10.1002/ijc.32283

12. Khan SR, Chaker L, Ruiter R, Aerts JGJV, Hofman A, Dehghan A, et al. Thyroid Function and Cancer Risk: The Rotterdam Study. J Clin Endocrinol Metab. 2016 Dec;101(12):5030–5036. https://doi.org/10.1210/jc.2016-2104

13. Wang Y, Zhou R, Wang J. Relationship between Hypothyroidism and Endometrial Cancer. Aging Dis. 2019 Feb;10(1):190–196. https://doi.org/10.14336/AD.2018.0224

14. Krashin E, Piekiełko-Witkowska A, Ellis M, Ashur-Fabian O. Thyroid Hormones and Cancer: A Comprehensive Review of Preclinical and Clinical Studies. Front Endocrinol (Lausanne). 2019;10:59. https://doi.org/10.3389/fendo.2019.00059

15. Maruzzo M, Verzoni E, Vitale MG, Dionese M, Buti S, Galli L, et al. Prognostic Value of Thyroid Hormone Ratio in Patients With Advanced Metastatic Renal Cell Carcinoma: Results From the Threefour Study (Meet-URO 14). Front Oncol. 2021;11:787835. https://doi.org/10.3389/fonc.2021.787835

16. Wu CC, Islam MM, Nguyen PA, Poly TN, Wang CH, Iqbal U, et al. Risk of cancer in long-term levothyroxine users: Retrospective population-based study. Cancer Sci. 2021 Jun;112(6):2533–2541. https://doi.org/10.1111/cas.14908

17. Voulgari PV, Venetsanopoulou AI, Kalpourtzi N, Gavana M, Vantarakis A, Hadjichristodoulou C, et al. Thyroid dysfunction in Greece: Results from the national health examination survey EMENO. PLoS One. 2022;17(3):e0264388. https://doi.org/10.1371/journal.pone.0264388

18. Chaker L, Bianco AC, Jonklaas J, Peeters RP. Hypothyroidism. Lancet. 2017 Sep 23;390(10101):1550–1562. https://doi.org/10.1016/S0140-6736(17)30703-1

19. Fliers E, Boelen A. An update on non-thyroidal illness syndrome. J Endocrinol Invest. 2021 Aug;44(8):1597–1607. https://doi.org/10.1007/s40618-020-01482-4

20. Guo J, Hong Y, Wang Z, Li Y. Analysis of the Incidence of Euthyroid Sick Syndrome in Comprehensive Intensive Care Units and Related Risk Factors. Front Endocrinol (Lausanne). 2021;12:656641. https://doi.org/10.3389/fendo.2021.656641

21. Frantsiyants EM, Bandovkina VA, Moiseenko TI, Myagkova TY, Chalabova TG, Adamyan ML, et al. Changes in the functional activity of the thyroid gland in patients with tumors of the ovary left after hysterectomy. International Journal of Applied and Fundamental Research. 2015;(8-1):59–62. (In Russ.).

22. Kozlova MB, Frantziyantz EM, Vladimirova LYu, Anapalyan VKh, Bandovkina VA, Svetitskaya YaV, et al. Thyroid and glucocorticoid status of patients with benign and malignant pathology of the breast. Siberian Journal of Oncology. 2009;(4):52–56. (In Russ.).

23. Kozlova MB, Frantsiyants EM, Salatova AM, Komarova EF, Pogorelova YuA. Primary tumors and their metastases to the brain: particularities of influence on the systemic status of thyroid hormones and cortisol. Fundamental Research. 2014;(7- 1):81–86. (In Russ.).

24. Kotieva IM, Kit OI, Frantsiyants EM, Bandovkina VA, Kaplieva IV, Pogorelova YuA, et al. Hormone levels in thyroid tissues in the dynamics of growth of transplantable b16/f10 melanoma in female mice with chronic neurogenic pain. News of Higher Educational Institutions. The North Caucasus region. Series: Natural Sciences. 2017;(4-2(196-2)):76–83. (In Russ.).

25. Kit OI, Frantsiyants EM, Bandovkina VA, Cheryarina ND, Islamova EF, Cherkes MA, et al. Features of thyroid status in female and male C57/BL6 mice during the growth of transfused melanoma B16/F10. International Journal of Experimental Education. 2016;(10-2):257–258. (In Russ.).

26. Kit OI, Frantsiyants EM, Bandovkina VA, Cheryarina ND. Gender differences in the function of thyroid gland in the dynamics of the growth of transplantable B16/F10 melanoma in mice. Russian Journal of Oncology. 2016;21(5):253–258. (In Russ.).

27. Franzyants EM, Bandovkina VA, Kaplieva IV, Tripitaki LK, Cheryarina ND, Dimitriadi SN, et al. The effect of the growth of primary melanoma b16/f10 on the functioning of the hypothalamic-pituitary-adrenal and thyroid axes of the body in male and female mice. News of higher educational institutions. News of higher educational institutions. The North Caucasus Region. Series: Natural Sciences. 2017;(3-2(195-2)):118–124. (In Russ.).

28. Asai K, Shirakabe A, Kiuchi K, Kobayashi N, Okazaki H, Matsushita M, et al. Relation of Low Triiodothyronine Syndrome Associated With Aging and Malnutrition to Adverse Outcome in Patients With Acute Heart Failure. Am J Cardiol. 2020 Feb 1;125(3):427–435. https://doi.org/10.1016/j.amjcard.2019.10.051

29. Zyla LE, Cano R, Gómez S, Escudero A, Rey L, Santiano FE, et al. Effects of thyroxine on apoptosis and proliferation of mammary tumors. Mol Cell Endocrinol. 2021 Dec 1;538:111454. https://doi.org/10.1016/j.mce.2021.111454

30. Calissendorff J, Falhammar H. To Treat or Not to Treat Subclinical Hypothyroidism, What Is the Evidence? Medicina (Kaunas). 2020 Jan 19;56(1):40. https://doi.org/10.3390/medicina56010040


Supplementary files

Review

For citations:


Frantsiyants E.M., Bandovkina V.A., Kaplieva I.V., Surikova E.I., Neskubina I.V., Pogorelova Yu.A., Trepitaki L.K., Cheryarina N.D., Nemashkalova L.A., Arakelova A.Yu. Changes in pathophysiology of tumor growth and functional activity of the hypothalamic-pituitary-thyroid axis in rats of both sexes with the development of Guerin's carcinoma on the background of hypothyroidism. South Russian Journal of Cancer. 2022;3(4):26-39. https://doi.org/10.37748/2686-9039-2022-3-4-3

Views: 451


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2686-9039 (Online)