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.
Aims: to study the content of regulatory peptides in the hypothalamus and pituitary gland, as well as sex steroids in the gonads in rats of both sexes with Guerin’s carcinoma against the background of hypothyroidism. Materials and methods. Our experiment was performed in white outbred rats of both sexes with induced hypothyroidism, against the background of which Guerin’s carcinoma was transplanted. In 1% homogenates of the pituitary and the hypothalamus and in 10% homogenates of the gonads in the animals from the main and reference groups, the levels of GnRH (Casabio, China) were determined by the ELISA method using standard kits, and the content of LH, FSH, estradiol (E2), testosterone (T) and progesterone (P4) by the RIA method (Immunotech, Czech Republic). Statistical analysis of the results was performed using the Statistica 10.0 software package. Results. In females of the main group, the level of GnRH in the hypothalamus increased by 1.6 times, but the content of LH and FSH in the pituitary gland decreased, while in males the content of GnRH decreased by 1.4 times and FSH by 1.6 times compared with the intact animals. In the gonads of females of the main group, the content of E2 and T decreased by 1.3 times, but the level of P4 increased by 4.7 times, while in males the T production decreased by 7.1 times. Hypothyroidism, against the background of which Guerin’s carcinoma developed, had a significant effect both on the central links of the HPG axis and the peripheral ones, producing an additional hormonal imbalance in sex steroids
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.
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