Influence of hypothyroidism on the hypothalamic-pituitarygonadal axis in rats with Guerin's tumor

National Medical Research Centre for Oncology

Russia, Rostov-on-Don

The thyroid and the gonadal (HPG) regulatory axes are interconnected and act together as a single system and their imbalance leads to pathological responses of the organism [1, 2]. The involvement of thyroid and sex hormones in the development of the malignant process has been discussed for many decades.

The aim of our research work was to study the concentrations of regulatory peptides in the hypothalamus and the pituitary glands, as well as sex steroids in the gonads, the tumor and its perifocal zone in rats of both sexes with Guerin's carcinoma growing in the presence of hypothyroidism.

Materials and methods . Albino outbred rats of both sexes (n=30) weighing 150 g or more received Mercazolil at a daily dose of 2.5 mg/100 g of body weight (the total dose of 75 mg/100 g of body 48 Cardiometry, Issue 24, November 2022

weight) for 30 days. In blood of the animals, the levels of thyroid hormones T3 and T4 as well as TSH were determined. After persistent hypothyroidism, male and female animals of the main group were inoculated with 0.5 ml of a suspension of the Guerin's carcinoma cells in a 1:5 dilution with saline solution under the skin of the back. The reference group consisted of rats of both sexes (n=30) with subcutaneous inoculation of the Guerin's carcinoma cells at the same dose and volume as in the main group. In the rats of the main test group and in the reference group, after 14 days of the tumor growth, using the standard ELISA methods, in homogenates of their organs and tumors, we determined concentrations of the hypothalamic gonadotropin-releasing hormone (GnRH) and the pituitary tropic hormones LH, FSH as well as sex steroids: estradiol (E2), testosterone (T) and progesterone (P4).

Results . The growth of Guerin's carcinoma in presence of hypothyroidism demonstrated its own sex-related characteristics, since the central regulatory structures of the HPG axis - the hypothalamus and the pituitary glands in the males - were found to be more susceptible to changes in response to suppression of the thyroid gland function than in females. In the males of the main group, compared with the reference group, the level of LH-releasing decreased by a factor of 4, while LH in the pituitary gland increased by a factor of 1.3, but however FSH decreased by a factor of 2.2. In the females of the main group, only a decrease in the level of pituitary FSH by a factor of 3.6 was found. Also, in the male tumor-bearers, in response to hypothyroidism, in their testicles, suppression of steroidogenesis was observed: the level of T decreased by a factor of 4, P4 increased by a factor of 1.9, and the content of E2 did not change, while the ratio of E2/T increased by more than 4 times. In the gonads of the females in the main group, compared with the reference, the concentration of all steroids increased: E2 by 2 times, T by 1.8 times and P4 by 1.7 times, but the E2/T ratio did not change. However, the tendency of the changes in steroid hormones in the tumor in response to induced hypothyroidism in the females and the males was the same: the concentration of E2 decreased on average by 1.4 times, but the concentration of T increased on average by 1.8 times and P4 by 1.6 times and 3.9 times, respectively, while the ratio of E2/T decreased in the females by 2.3 times and in the males by 7.7 times.

Conclusion . Hypothyroidism as comorbidity for a malignant process makes its influence on all links of the HPG axis and also alters the local synthesis/uptake of steroid hormones by the tumor.