The deiodination of thyroxine to triiodothyronine in the testes of patients with prostate cancer

Abstract

Until recently metabolism and expression of thyroid hormones was considered not to occur in the tissues of the testes. Lately, specific receptors for triiodothyronine have been found in the nuclei of human testicular cells which shows that testicular tissue requires hormonal action [9].

The aim of the present study was to evaluate if the prohormone thyroxine is converted into triiodothyronine within human testes (resected because of prostatic carcinoma) and if hormonal therapy with dihydrostilbestrol (DES), a testosterone antagonist, affects production of the active thyroid hormone. Our earlier studies showed a complete lack of iodothyronine 5′-deiodinase activity in prostatic carcinoma (PC) [7]. The present material consisted of testes from 21 patients with PCs. According to Whitmore's classification 13 patients were at stage C with mean PSA of 70.15 ng/ml and 8 were at stage D with mean PSA of 308.73 ng/ml. Before castration 6 patients (3 stage C and 3 stage D) were pretreated with 3 mg DES daily for 3 days. The resected testes were homogenized and ultracentrifuged. The obtained microsomal fraction was the source of thyroxine 5′-deiodinase (T4–5′-D). In 15 patients, in whom the primary approach was surgical, the specific T4–5′-D activity was not different between stage C and D patients (mean±SD): 19.52±12.55 vs. 22.07±12.68 fmolde novo produced triiodothyronine/min/mg of microsomal protein, respectively. However, in 6 patients pretreated with DES the activity was significantly decreased regardless of the degree of differentiation of the prostate carcinoma: 0.70±0.68 fmol T3/min/mg for stage C and 2.6±4.5 fmol/min/mg for stage D patients. The results suggest that iodothyronine 5′-deiodinase is localized in human testes, catalyzes prohormone biotransformation into active hormone and that DES pretreatment before surgery significantly inhibits testicular T4–5′-D activity.