Endocrine Abstracts

Introduction: Adrenocortical carcinoma (ACC) is characterized by the high malignancy of the lesion, poor prognosis and high mortality rate. The surgical treatment and available chemotherapy have generally low efficacy so the search for new therapeutic options is still necessary. Some research indicated that thiazolidinediones (TZDs)–synthetic ligands of peroxisome proliferator-activated receptor γ (PPARγ) have oncostatic action on neoplasm, including endocrine tumours. Moreover, previous investigations (ours and others) have shown the inhibitory effect of TZDs on the growth of human adrenocortical cancer in vitro and in vivo conditions. Therefore, in the present study, we decided to examine whether TZDs influence the secretion of adrenocortical hormones.

Materials and methods: The experiment was conducted on human adrenocortical carcinoma line H295R, whose cells posses the ability to produce cortisol, aldosterone and adrenal androgens. The cancer cells were treated with two TZDs – rosiglitazone (ROS) or pioglitazone (PIO) at the concentrations 10⁻⁸–10⁻⁵ M for 3 days. In the culture medium, we measured the levels of the following hormones: aldosterone, cortisol, DHEAS, androstendione and 17-hydroxyprogesterone by using chemiluminescence immunoassay and RIA.

Results: Both TZDs at most of the concentrations have increased DHEAs level. Besides, PIO stimulated cortisol secretion by cancer cells at all tested concentrations and ROS increased the hormone level only at the highest concentration. However, TZDs did not change significantly the levels of other adrenal hormones.

Conclusion: Agonists of PPARγ, despite the inhibitory effect on the growth of adrenocortical carcinoma, do not reduce the hormonal activity of cancer cells. So, it can be presumed that oncostatic action of TZDs and their influence on the synthesis of adrenal hormones are unrelated and depend on a different intracellular mechanism.