Endocrine Abstracts

Introduction: Thyroidal status can play important role in progression mammary gland tumour growth. We have already shown that hypothyroidism induced by application of 6-n-propylthiouracil (PTU) – inhibitor of type I iodothyronine 5′-deiodinase (5′-DI) – prolonged tumour latency and reduced number, volume and burden of 1-methyl-1-nitrosourea (MNU) induced rat mammary gland tumours in Sprague–Dawley female rats.¹

Design: 4-Hydroxy-2-mercapto-6-methylpyrimidine (MTU) is a derivative of PTU, thus the effects of PTU or MTU on tumour progression as well as expression of selected nuclear receptors in MNU-induced mammary gland tumours and rat livers were investigated in this experiment. Female Sprague–Dawley rats were given 50 mg/kg MNU i.p. on 62nd, 109th, and 150th day of age. From 56th day of age, the PTU group of MNU treated rats was receiving PTU (1 mg/kg) intragastrically 3× per week and MTU group of MNU animals 0.1% w/v of MTU in drinking water until the end of experiment.

Results: Administration of PTU to MNU treated animals markedly reduced number of tumours when compared to MNU group of animals. Furthermore, we did not find any tumour in the MTU group of animals. However we have detected significantly reduced body weight when compared to PTU, untreated MNU animals and healthy control animals. Administration of MTU resulted in reduced expression of RARα, RXRα and increased expression of RARγ in rat liver (vs MNU and C). Using EMSA method, we have found significantly reduced amount of nuclear receptor-hormone responsive elements (RARE, TRE, and VDRE) complex in tumours of PTU treated animals (vs MNU animals). Since MTU did not affect 5′-DI in the liver, the mechanism of MTU action needs further investigation.

Disclosure: This work was supported by the grant APVV-0160-11, the VEGA grant 2/0171/14, and the Centre of Excellence CEMAN grant.

Reference: 1. Macejova et al. Mol. Cell. Endocrinol. 2005 244 (1–2) 47–56.