Aims: to study the features of the functioning of the hypothalamic-pituitary-gonadal axis (HPGA) regulation in male rats at the stages of liver metastasizing. Materials and methods. Our research work was performed in 30 outbred male rats. Metastases in the liver were produced by implantation of sarcoma 45 (S45) cells into the spleen, which was previously positioned under the skin. The time spans of the study are 5 weeks (the pre-metastatic stage) and 7 weeks (the metastatic stage) after tumor cell transplantation. In the tissues, the content of the following hormones was determined by RIA: luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), total testosterone (Ttot), progesterone (P4); by ELISA we determined the content of the following hormones: gonadotropin-releasing hormone (GnRH), free testosterone (Tfr) and estrone (E1). Results. At all stages of the study, the level of GnRH in the hypothalamus decreased by more than 2.0 times; in the pituitary gland, the hormone levels had multidirectional dynamics: LH decreased by 1.6 times, and FSH increased by more than 6.0 times. Liver metastases were characterized by high levels of E1 and Ttot. In the gonads, a high level of P4 was recorded and concentrations of both forms of testosterone were reduced. The concentrations of E2 (by 1.6 times), Tfr (by 4.8 times) increased in blood, and the level of Ttot decreased (by 1.9 times). The salient features of HPGA in the presence of two metastasis sites (liver and lungs) were as follows: in blood, a 2.0 times lower increase in the LH and Tfr contents, a 1.6 times greater increase in E2, an increase in P4 (2.6 times), 1, 4 times lower level of FSH; in the gonads, there are found lower levels of P4, E1, but higher levels of Tfr and Ttot; in liver metastases, a greater increase in P4 (5.2 times), E1 (2.2 times) and Tfr (2.0 times) is recorded. Conclusion. Metastasizing to the liver was accompanied by activation of HPGA with the maximum accumulation of reactogenic E1 in liver metastases in rats with two metastasis sites that may indicate their more severe malignancy and ability to metastasize to the lungs.

The aim was to study changes in the functioning of the hypothalamic-pituitary-gonadal (HPG) axis in BALB/c Nude mice of both sexes with multiple primary malignant tumors (MPMTs). The BALB/c Nude mice (n=84) of both sexes were divided into groups as follows: intact males and females (n=14), a reference group of mice of both sexes with standard subcutaneous inoculation of B16/F10 melanoma (n=14); the main group of mice with the reproduction of the MPMT model (n=14); B16/ F10 melanoma and Lewis carcinoma were inoculated into mice sequentially subcutaneously on two sides: one on the left side and the other on the right side. After 15 days of the growth of the malignant tumors, GnRH, LH and FSH contents were determined by ELISA using standard kits in 1% of the homogenates of the hypothalamic and pituitary tissues, and estradiol content (E2) was determined in 10% homogenates of ovaries and testes, as well concentrations of testosterone (T) and progesterone (P4) were identified in blood serum with the standard RIA kits (Immunotech, Czech Republic). Results. In the hypothalamus in females of the reference and main groups, the level of GnRH increased by 2.5-4 times, and in males it decreased by an average of 3.1 times; in response to those changes in animals of both sexes in the reference group and in the main group only in females in the pituitary gland the level of LH increased by 1.3-1.6 times, however a decrease in FSH in all groups was more pronounced in females: by 7.8-13.7 times and less pronounced in males: by 1.4-1.7 times (р˂0, 05). In the gonads of females, the level of E2 increased, but the levels of T and P4 decreased, while P4 increased in males. Blood parameters did not reflect hormonal changes in the organs. Conclusion. Abnormalities in the HHG axis performance, along with primary immunodeficiency, play a decisive role in overcoming antitumor protection for uncharacteristic malignant tumors.

Improving the survival of cancer patients contributes to a growing number of patients with chronic comorbidities, including diabetes mellitus (DM). Moreover, higher risk of cancer development in patients with DM and poor prognosis determine the importance of studying the mechanisms mediating the effect of altered glucose metabolism made on the growth and metastasis of malignant tumors [3,4]. The polyetiology of both pathologies and the presence of research studies that do not confirm a direct relationship between DM and the development of malignant neoplasms indicate the complex nature of their relationship with the possible context-dependent regulation of many cellular processes associated with carcinogenesis and the development of DM [1,2]. An important role in the processes of the regulation is played by an imbalance in the system of sex hormones.

ФГБОУ «Ростовский государственный медицинский университет», Ростов-на-Дону Одной из основных гипотез о механизмах взаимосвязи сахарного диабета (СД) и развития онкопатологии является дисбаланс в системе половых гормонов, влияющий на пролиферацию, миграцию, инвазию опухолевых клеток. Цель исследования: изучение особенностей влияния СД как сопутствующего злокачественному росту заболевания на содержание половых гормонов и их рецепторов в ткани опухоли разной гистоструктуры и ее перифокальной зоны у экспериментальных животных разного вида. Использовали самок белых нелинейных крыс (n=36) и мышей BALB/c Nude (n=28). Контрольные группы -самостоятельный рост перевивной опухоли (карцинома Герена (КГ) у крыс, карцинома легких Льюиса (LLC) у мышей), основные группы -рост опухоли на фоне СД, индуцированного аллоксаном. В опухоли и ее перифокальной зоне определяли содержание эстрадиола, тестостерона, прогестерона, рецепторов эстрогенов, прогестерона и андрогенов методом ИФА (Casabio, Китай). Результаты подчеркивают значимую роль коморбидной патологии СД, которая не только активировала рост опухоли, но и усилила метастазирование, формируя агрессивный фенотип опухоли и снижая продолжительность жизни животных. КГ, растущая на фоне СД, была меньшего объема, но обладала значительным метастатическим потенциалом. На фоне ее диссеминации содержание эстрогенов и прогестерона и их рецепторов в ткани опухоли превышало уровень в опухоли контрольных животных. В противоположность этому LLC, растущая на фоне СД, содержала более высокую концентрацию половых гормонов, но более низкий уровень их рецепторов, обладая значительно большим, чем в контроле, объемом, при этом метастазы не были выявлены. Изучение опухолей сходной гистоструктуры, но различного происхождения (эпителий матки, легочной эпителий) и развивающихся в различном физиологическом контексте, помогло оценить особенности влияния СД, сопутствующего злокачественному росту, на изменение гормонального статуса опухолевой ткани и ее перифокальной зоны, который участвует в молекулярной связи между СД и прогрессированием опухоли. Ключевые слова: онкопатология, коморбидная патология, сахарный диабет, диссеминация, карцинома Герена, карцинома Льюиса, половые гормоны, рецепторы гормонов.