Stetsuk Ye. V., Shepytko V. I., Boruta N. V., Rud M. V., Skotarenko T. A., Vilkhova O. V.

MORPHOGENESIS OF PERITUBULAR MACROPHAGES IN THE INTERSTITIAL SPACE OF THE RAT TESTES UNDER CENTRAL BLOCKING OF LUTEINISING HORMONE SYNTHESIS BY TRYPTORELIN ON DAYS 180 AND 270 OF OBSERVATION

---

Show/Download

About the author:

Stetsuk Ye. V., Shepytko V. I., Boruta N. V., Rud M. V., Skotarenko T. A., Vilkhova O. V.

Heading:

MORPHOLOGY

Type of article:

Scientific article

Annotation:

Luteinising hormone (LH) is a glycoprotein hormone, which is formed in the adenohypophysis. Its biological role is to regulate the functions of the human sexual sphere. Together with follicle-stimulating hormone, they are classified as gonadotropic hormones, the synthesis and secretion of which is stimulated by hypothalamic gonadoliberin. Testosterone, the production of which is stimulated by the release of LH, through the activation of testicular interstitial endocrinocytes leads to the activation of macrophage polarisation under the M2 phenotype (anti-inflammatory). Testosterone has a significant impact on the functional state of macrophages in the body. Under the influence of testosterone, macrophage polarisation towards the pro-inflammatory phenotype (M1) is inhibited, resulting in a reduction in the production of cytokines such as interleukin 1β (IL-1β) and interleukin 6 (IL-6). Cytokines suppress steroidogenesis at the level of the adrenal glands, testes and ovaries. In the adrenal glands, macrophages and lymphocytes physiologically infiltrate the adrenal cortex extensively, whereas adrenocortical and chromaffin cells also produce cytokines such as IL-1, IL-6, TNFalpha, leukaemia inhibitory factor (LIF) and IL-18, playing a key role in immune-adrenocortical communication. Thus, testosterone has a significant anti-inflammatory and immunomodulatory effect, and in conditions of its deficiency, tissue damage may develop due to excessive polarisation of macrophages by the M1 phenotype. The experiment was performed on 20 white male rats randomly selected into 2 groups: control (10 animals) and experimental (10 animals). Animals in the experimental group were injected with a solution of tryptorelin acetate at the dose of 0.3 mg of active ingredient per kg of animal weight to simulate central blocking of luteinising hormone synthesis. The studies were performed using an electron microscope. It has been established that under the influence of central blockade of LH synthesis, the antigen-presenting cells of the interstitial space of the testis, in particular macrophages, are rearranged. These modifications indicate an inversion of their polarisation, which in turn leads to microscopic reorganisation of cells, specifically their activation (M1) to perform certain functional activity in the organ.

Tags:

Bibliography:

1. Almeida S, Rato L, Sousa M, Alves MG, Oliveira PF. Fertility and Sperm Quality in the Aging Male. Curr Pharm Des. 2017;23(30):4429- 4437. DOI: 10.2174/1381612823666170503150313.
2. Atallah A, Mhaouty-Kodja S, Grange-Messent V. Chronic depletion of gonadal testosterone leads to blood-brain barrier dysfunction and inflammation in male mice. J Cereb Blood Flow Metab. 2017;37(9):3161-3175. DOI: 10.1177/0271678 X16683961.
3. Lokka E, Lintukorpi L, Cisneros-Montalvo S, Mäkelä JA, Tyystjärvi S, Ojasalo V, et al. Generation, localization and functions of macrophages during the development of testis. Nat Commun. 2020;11:4375. DOI: 10.1038/s41467-020-18206-0.
4. Rehman A, Pacher P, Haskó G. Role of Macrophages in the Endocrine System. Trends Endocrinol Metab. 2021 Apr;32(4):238-256. DOI: 10.1016/j.tem.2020. 12.001.
5. Hotta Y, Kataoka T, Kimura K. Testosterone Deficiency and Endothelial Dysfunction: Nitric Oxide, Asymmetric Dimethylarginine, and Endothelial Progenitor Cells. Sex Med Rev. 2019;7(4):661-668. DOI: 10.1016/j.sxmr. 2019.02.005.
6. Merseburger AS, Hupe MC. An Update on Triptorelin: Current Thinking on Androgen Deprivation Therapy for Prostate Cancer. Adv Ther. 2016;33(7):1072-93. DOI: 10.1007/s12325-016-0351-4.
7. Wang M, Yang Y, Cansever D, Wang Y, Kantores C, Messiaen S, et al. Two populations of self-maintaining monocyte-independent macrophages exist in adult epididymis and testis. 2021 Jan 5;118(1):e2013686117. DOI: 10.1073/ pnas.2013686117.
8. Mossadegh-Keller N, Sieweke MH. Testicular macrophages: Guardians of fertility. Cell Immunol. 2018;330:120-125. DOI: 10.1016/j. cellimm.2018.03. 009.
9. Botté MC, Lerrant Y, Lozach A, Bérault A, Counis R, Kottler ML. LH down-regulates gonadotropin-releasing hormone (GnRH) receptor, but not GnRH, mRNA levels in the rat testis. J Endocrinol. 1999;162(3):409-415. DOI: 10.1677/joe.0.1620409.
10. Bahriy MM, Dibrova VA, Popadynets OH, Hryshchuk MI. Metodyky morfolohichnykh doslidzhen. Vinnytsya: Nova knyha; 2016. 328 s. [in Ukrainian].
11. Stetsuk YeV, Akimov OYe, Shepitko KV, Goltsev AN. Structural organization of stromal and parenchymal components of rat testes during central deprivation of testosterone synthesis on the 180 day of the experiment. World of medicine and biology. 2020;72(2):203-207. DOI: 10.26724/2079-8334-2020-2-72-203-207.
12. Stetsuk YeV, Akimov OYe, Shepitko KV, Goltsev AN. Role of nitric oxide in development of fibrotic changes in rats’ testes after 270 day central deprivation of testosterone synthesis. World of medicine and biology. 2020;73(3):211-215. DOI: 10.26724/2079-8334-2020-3-73-215-219.

Publication of the article:

«Bulletin of problems biology and medicine», 2023 Issue 2, 169, 393-396 pages, index UDC 616.682:599.323.452+615.357:577.169

DOI:

10.29254/2077-4214-2023-2-169-393-396