Differences in the functioning of the hypothalamic-pituitarygonadal axis of regulation in male rats at one (liver) site and two (liver and lungs) sites of metastasis of sarcoma 45 in the experiment

Abstract

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.